Rheumatol Int DOI 10.1007/s00296-015-3297-y
Rheumatology INTERNATIONAL
REVIEW ARTICLE - REVIEW HEALTH SERVICES
Polymyalgia rheumatica: strategies for efficient practice and quality assurance Michael Schirmer1 · Christian Dejaco2 · Bhaskar Dasgupta3 · Eric L. Matteson4
Received: 16 February 2015 / Accepted: 21 May 2015 © Springer-Verlag Berlin Heidelberg 2015
Abstract Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease in persons over the age of 50 years. There are many diseases which mimic PMR, for which reason a careful diagnostic approach is required. While it is thought to be exquisitely responsive to glucocorticosteroid therapy, many patients respond incompletely and/or develop serious side effects over the protracted disease course. Improved methods for classification and disease assessment together with standardized treatment approaches and outcome assessments can serve to improve the care of patients with this disease. Keywords Polymyalgia rheumatica · Quality measures · Diagnosis · Classification criteria · Treatment · Outcome
Introduction Polymyalgia rheumatica (PMR) is the most common inflammatory rheumatic disease in the elderly, predominantly
* Eric L. Matteson
[email protected] Michael Schirmer
[email protected] 1
Department of Internal Medicine, Medical University of Innsbruck, Innsbruck, Austria
2
Division of Rheumatology and Immunology, Medical University of Graz, Graz, Austria
3
Department of Rheumatology, Southend University Hospital, Westcliff‑on‑Sea, UK
4
Division of Rheumatology, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, MN, USA
occurring in females, with a prevalence of >7/1000 among persons older than 50 years, increasing to >4/100 for persons ages 90–95 years [1, 2]. PMR is a heterogeneous condition commonly managed with low-dose glucocorticosteroid (GC) therapy, with initial doses of 15–20 mg a day of prednisone equivalent. The course of PMR can be protracted, with disease duration of 3 years or more and sometimes lifelong. Critical evaluation of this disease reveals that it is not always easily classified, diagnosed or treated. Several conditions can present with polymyalgic onset, and there is an overlap with inflammatory arthritis as well as large vessel vasculitis in the form of giant cell arteritis (GCA), which occurs in 10–30 % of patients with PMR. The response to GC therapy is variable, and many patients develop significant cardiovascular and other GC-related side effects over the course of the disease. In terms of response to GC therapy, three categories of disease course have been proposed: a rapid response to GCs without significant relapse, a rapid response requiring extended treatment and an incomplete resolution of symptoms requiring increased doses of GC and extended treatment [3]. The recent European League Against Rheumatism/American College of Rheumatology (EULAR/ACR) classification criteria study, which prospectively evaluated disease features and response to therapy, and a study from the UK suggest that only 52–56 % of patients have a complete response to GC when assessed at 4, 12 and 26 weeks [4–6]. These and other reports strongly emphasize the need for better, safer therapies in PMR and that the initial response to GC therapy can predict long-term clinical outcomes [5, 7–9]. The large burden of PMR, diagnostic uncertainty and heterogenous course demands expert disease management and assessment of quality of care (QOC) aimed toward
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therapeutic efficiency and prevention of adverse events [7]. In an effort to address these issues, national guidelines and audit standards for diagnosis and management of PMR are needed such as the guidelines published by the British Society of Rheumatology and the British Health Professionals in Rheumatology, as well as guidelines being proposed by EULAR/ACR [7, 10]. This review summarizes current strategies both for efficient practice and quality assurance in routine clinical work with PMR patients.
Quality of care in PMR Quality-of-care standards consist of a combination of (1) early and accurate diagnosis recognizing the heterogeneity of presentation and many possible mimics, (2) individualized adequate treatment with appropriate monitoring of disease activity to document treatment responsiveness and assess relapses as early as possible and (3) prevention of, and regular assessments of GC-related side effects, especially diabetes-induced complications, osteoporotic fractures, cardiovascular events and cataracts [9]. 1. Early and accurate diagnosis at initial presentation Strategies for evaluation of a patient with suspected PMR are essential for ensuring accurate diagnosis, setting a course of treatment and long-term follow-up of the patient. These include the following steps: • To evaluate symptoms and signs specific for PMR such as bilateral proximal pain and stiffness. • To exclude alternative diagnoses in cases of new-onset characteristic proximal muscle and joint pain and stiffness, especially of the shoulders, hips and neck. • To evaluate additional coexistent medical comorbidities which bear on the disease and its treatment, including giant cell arteritis, osteoporosis, diabetes mellitus, cardiovascular manifestations and cataracts. Of critical importance is the early and ongoing assessment of patients for evidence of giant cell arteritis, as this requires urgent institution of high-dose steroid. At initial presentation, polymyalgic symptoms of the elderly patient may signify other possibly life-threatening illness causing these symptoms [11–13]. The “polymyalgia syndrome” may reflect a number of other serious medical conditions, including bacterial endocarditis, systemic vasculitis or malignancy (Fig. 1). Other medical conditions presenting with complaints of proximal stiffness include rheumatoid arthritis or late-onset undifferentiated spondyloarthritis, connective tissue diseases, parkinsonism,
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hypothyroidism, preexisting fibromyalgia, osteoarthritis and shoulder conditions. Ultrasonography of shoulders and hips (characteristic PMR lesions, e.g., bursitis, bicipital tenosynovitis, joint effusion described by Dasgupta et al. [6]), peripheral joints (for synovitis) and temporal arteries (if there is suspicion of GCA) may be most helpful in diagnosis and is helpful in assessing response to GC therapy [14, 15]. Quality of care in PMR demands that the diagnosis be made in a safe stepwise manner based on essential symptoms including new-onset bilateral shoulder/hip pain and stiffness in people above 50 years age (Tables 1, 2). Essential exclusions such as active infection, cancer, rheumatoid arthritis and others must be pursued through clinical evaluation and a minimum set of laboratory investigations to exclude other mimics. Careful evaluation of clinical and laboratory response to low-dose GC and constant vigilance for alternate pathology on follow-up is essential to good disease assessment. 2. Rapid and adequate treatment with focus on low adverse effects
• Glucocorticosteroids are considered the current standard of care for treatment of PMR. Other medications such as methotrexate are sometimes used as GC-sparing agents, but thus far, no other agents have gained acceptance or been approved for treatment of PMR. The initial recommended dose ranges from 15 mg prednisolone daily [proposed by the British Society of Rheumatology guidelines [8] and 25 mg daily [proposed by the German Society of Internal Medicine [16]. The EULAR/ ACR guidelines endorse 12.5–25 mg a day prednisone equivalent as a starting dose [10]; in some cases, an alternative i.m. depomedrol regiment may be considered [17]. The GC dose for the individual patient needs to be tailored to disease severity, comorbidities and risks from GC therapy as well as patient choice [3]. GCs are given as a single morning dose and usually but not always result in rapid improvement in disease symptoms. At least 70 % of PMR patients report global improvement with normalization of the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) within 3 to 4 weeks [4, 18]. If the initial response to treatment is not dramatic, other possible diagnoses and adjuvant therapies may be considered. Higher doses of prednisone are not infrequently used to treat myalgic syndromes deemed “poorly responsive PMR” with apparent response, which is often non-specific and generally will only contribute to delays in diagnosing the actual underlying condition (such as malignancies or bacterial endocarditis) and/or lead to excessive GC-related morbidity.
Rheumatol Int Fig. 1 Assessment of proximal pain and stiffness—differential diagnoses of new-onset bilateral shoulder pain. ©The Author 2009. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email:
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• Glucocorticosteroids should be tapered slowly, e.g., by 1 mg every 4–8 weeks until discontinuation. Slow tapering following a low initial prednisone dose results in better outcomes than high starting doses and a quick tapering regimen [19]. Up to 70 % of patients relapse if GCs are tapered too quickly, and the hazard of having a relapse has been found to be fourfold higher if GC tapering rate is rapid (from 20 to 3 mg over 8 weeks) compared with slow dose reduction (from 20 to 13 mg over the first 8 weeks of therapy) [20]. Recent studies indicate that patients usually require about 18–36 months of CS therapy [21, 22].
• Glucocorticosteroids may be associated with significant adverse effects. Only the minimum effective dose should be used. Strategies for detection and management of adverse effects are strongly recommended, e.g., for psychological effects, excessive weight gain, bruising, diabetes, osteoporosis/insufficiency fractures, infections, arterial hypertension, cataracts, avascular necrosis and GC-induced myopathy. Patients with PMR have higher likelihood of having a history of myocardial infarction [odds ratio (OR) 1.78, 95 % CI 1.13, 2.82], peripheral vascular diseases (OR 2.21, 95 % CI 1.37, 3.60) and cerebro-
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Table 1 Scoring algorithm for classification of polymyalgia rheumatica (PMR), including ultrasound criterion Odds ratio (95 % CI) Points Clinical criteria Morning stiffness >45 min Hip pain or limited range of motion Normal RF or ACPA Absence of other joint pain
5.0 (2.8, 9.1) 1.4 (0.8, 2.6) 5.2 (2.1, 12.6) 2.2 (1.3, 4.0)
2 1 2 1
Ultrasound criteria At least one shoulder with subdeltoid bursitis and/or biceps tenosynovitis and/or glenohumeral synovitis (either posterior or axillary) and at least one hip with synovitis and/or trochanteric bursitis
2.6 (1.3, 5.3)
1*
Both shoulders with subdeltoid bursitis, biceps tenosynovitis or glenohumeral synovitis
2.1 (1.2, 3.7)
1*
Required criteria: age ≥50 years, bilateral shoulder aching and abnormal CRP and/or ESR (according to Dasgupta et al. [6]). The optimal cut point without using ultrasound is 4. A score of 4 or more is categorized as having PMR RF rheumatoid factor, ACPA anti-citrullinated protein antibody, CI confidence interval, ESR erythrocyte sedimentation rate, CRP C-reactive protein * p = 0.008 and p = 0.009 for these additional criteria, respectively. The optimal cut point is 5. A score of 5 or more is categorized as having PMR
vascular diseases (OR 1.60, 95 % CI 1.08, 2.39) [23]. These comorbidities increase costs (e.g., for hospital stays and imaging) compared with matched nonPMR subjects [24]. Management of comorbidities including cardiovascular risks such as hypertension, diabetes, hyperlipidemia, obesity and osteoporosis is necessary throughout the entire course of the disease. National and society guidelines are available for management of some comorbidities such as osteoporosis. • While beyond the scope of this review, there is a need for GC-sparing drugs for management of PMR. Unfortunately, there are no large studies that would support the role for other therapeutic agents or approaches than the use of GC. Methotrexate may be used in patients, especially in view of comorbidities which may worsen by GC therapy (such as diabetes, osteoporosis and/or glaucoma) [25–27]). There is no established benefit for any biological at the moment. Nonsteroidal anti-inflammatory agents have no value for management of PMR and are associated with considerable drug-related morbidity [28].
3. Regular and adequate monitoring of disease activity and early recognition of adverse effects
formed at these and interval visits for evaluation of disease flares or adverse effects. • The management aim is to achieve the optimal GC dose with appropriate balance between efficacy and minimal adverse events. It is important to treat the patient’s symptoms, not relying exclusively on frequent measurement of the acute-phase reactants (generally, the ESR and CRP) to guide treatment. The PMR activity score (as described below) appears helpful for diagnosing flares of PMR and may assist in everyday practice to decide how to change the GC dosage [29]. • Patient education about the disease and its treatment at diagnosis and throughout the course of the disease are essential to the QOC of these patients, in order to promote self-management, achieve good outcomes and reduce the burden of the disease- and therapy-related adverse events. To this end, PMR support groups such as PMRGCAUK in the UK and the Vasculitis Foundation in the US are vital to promoting public awareness and education on this condition. In summary, QOC in PMR ultimately depends on achieving a balance between benefits of treatment (primarily GCs) against risk and burden of adverse events in an efficient manner.
Current measurement of quality in PMR • Efficient and effective follow-up includes clinical reassessment of the patient after 1–2 weeks following initiation of GC therapy and then at 4- to 12-weekly intervals depending on the patients’ disease activity. Treatment compliance and comorbidity assessments should be per-
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1. Diagnostic quality There are a number of divergent diagnostic criteria which have been proposed for PMR, none of which have universal acceptance. Recently, a set of classification
Rheumatol Int Table 2 Minimum diagnostic set General items and symptoms Age of 50 years or older* Bilateral shoulder pain, shoulder pain* Bilateral pelvic girdle (hip) pain New onset (45 min in the last 24 h* Joint pain other than bilateral shoulder and bilateral pelvic girdle (hip) pain* Patient’s assessment of global disease activity and global pain* Fatigue, recent weight loss >2 kg Examination Resting systolic and diastolic blood pressure Physician’s assessment of global disease* Shoulder pain, ability to elevate the upper limbs* Hip pain or limited range of motion*, hip tenderness Peripheral synovitis (distal swelling, tenosynovitis or arthritis) Laboratory markers Erythrocyte sedimentation rate and/or C-reactive protein* Rheumatoid factor and/or anti-citrullinated protein antibody* Creatinine/urea, electrolytes and urine analysis Fasting blood glucose, cholesterol and triglycerides Thyroid-stimulating hormone Creatine kinase, liver function tests, alkaline phosphatase Complete blood cell count with differential Tuberculosis testing according to regional guidelines Imaging (ultrasonography or magnetic resonance imaging, optional) Uni- or bilateral subdeltoid bursitis/biceps tenosynovitis/glenohumeral synovitis/trochanteric bursitis/glenohumeral and hip effusion* Bone density measurement every 1–2 years according to regional guidelines Chest radiography Items used in the EULAR/ACR provisional classification criteria for PMR are marked by an asterisk
criteria were published as European League Against Rheumatism/American College of Rheumatology (EULAR/ ACR) provisional classification criteria for PMR [6]: These criteria were developed to group patients with this disease syndrome together for the purpose of better disease study. They incorporate the principal clinical disease features which characterize this disease. Uniquely, musculoskeletal ultrasonography was found to be useful in the classification of the disease as well as assessing response to therapy [4, 6]. Quality of diagnoses can then be assessed using the rate of changed diagnoses during follow-up. The scoring algorithm for classification of PMR is summarized in Table 1 and was developed based on morning stiffness >45 min (2 points), hip pain/limited range of motion (1 point), normal RF and/or ACPA (2 points) and
the absence of peripheral joint pain (1 point). A score ≥4 had 68 % sensitivity and 78 % specificity for discriminating all comparison subjects from PMR. The specificity was higher (88 %) for discriminating shoulder conditions from PMR and lower (65 %) for discriminating RA from PMR. The c-statistic for the scoring algorithm was 81 %. An alternative scoring algorithm included the ultrasound findings and improved the c-statistic to 82 %. With the ultrasound-based scoring algorithm, a score ≥5 had 66 % sensitivity and 81 % specificity for discriminating all comparison subjects from PMR. The specificity was higher (89 %) for discriminating shoulder conditions from PMR and lower (70 %) for discriminating RA from PMR. Using the new 2012 EULAR/ACR classification criteria in an Italian single-center study revealed an even higher
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sensitivity of 92.6 %. Inclusion of ultrasound increased specificity from 81.5 to 91.3 % in all cases and from 79.7 to 89.9 % in RA [30]. 2. Outcome quality Key outcome parameters for ongoing management of PMR have been prospectively evaluated for these domains [4]: Symptoms • Shoulder pain [yes/no], shoulder pain [VAS] • Hip pain [yes/no], hip pain [VAS] • Morning stiffness duration [minute]*, best performed by asking about severity at 7 a.m. or “on waking” according to an observational study by OMERACT [31] • Patient’s assessment of global disease activity [VAS, 0 = no activity, 10 = most active disease] • Patient’s assessment of global pain [VAS, 0 = no pain, 10 = unbearable pain]* • Patient assessment of fatigue [VAS]
morning stiffness duration (minutes × 0.1) + patient’s assessment of global pain (VAS) + physician’s assessment of global disease (VAS) + ability to elevate the upper limbs(0 − 3) + CRP(mg/dl) Remission is defined within the range from 0 to 1.5 [30], but Binard et al. [33] stress the importance of a prospective study to determine whether closely spaced PMR-AS determinations by rheumatologists and general practitioners improve flare diagnosis and reduce GC exposure in an inception cohort of PMR patients. 4. Assessment of adverse events For PMR, assessment of adverse events focuses on GCs and thus includes diabetes, osteoporosis/insufficiency fractures, infections, arterial hypertension, cataracts, avascular necrosis and GC-induced myopathy.
Future or proposed measurement of quality
Questionnaires (optional) • Modified Health Assessment Questionnaire (M-HAQ) • Short Form 36 (PCS and MCS) Physician-assessed outcomes • Physician’s assessment of global disease [VAS, 0 = no disease activity, 10 = activity highest]* • Ability to elevate the upper limbs [0 = above shoulder girdle, 1 = up to shoulder girdle, 2 = below shoulder girdle, 3 = none]* Laboratory markers • Erythrocyte sedimentation rate, C-reactive protein [mg/ dl]* Imaging • Ultrasonographic assessment of subdeltoid bursitis, biceps tenosynovitis, glenohumeral synovitis (either posterior or axillary), hip synovitis, hip effusion, trochanteric bursitis
3. Summary assessment of disease activity To detect early disease flares, Leeb et al. [32] proposed the PMR activity score (PMR-AS) as the sum of the abovementioned outcome parameters marked with an asterisk:
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Use of standardized assessment forms in routine clinical practice will certainly help to gather complete sets of PMR-related data at time of diagnosis and during followup as given in Tables 1 and 2. PMR is a disease which in most countries is diagnosed and followed in primary care practices, but patients with several comorbid conditions are more likely to be seen by rheumatologists [23]. Future strategies contributing to the improvement in QOC to patients with PMR include the implementation of standard diagnostic and diagnosis-exclusion testing, GC treatment algorithms, and adverse event detection and management, which will serve to rationalize the use of diagnostic investigations and referral to specialists, and improve disease outcomes while reducing drug-related side effects [34]. The use of standardized assessment forms at time of diagnosis and during follow-up will serve to validate the EULAR/ACR provisional classification criteria and the PMR activity score (PMR-AS) with the focus on applying them in routine clinical practice. As well, this strategy will enable assessment of definitions of relapse and remission for clinical use and evaluate treatment recommendations made in society disease management guidelines [8, 10, 35]. The implementation of existing standard preventative measures for GC-related complications (osteoporosis prophylaxis, diabetes monitoring, vaccination, etc.) using national and society guidelines will enhance physicians’ and patients’ awareness of these adverse effects and promote strategies for their prevention.
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The role for instruments to be used in the measuring quality of life (QOL) in PMR is still unresolved: QOL can be studied using the Modified Health Assessment Questionnaire (M-HAQ) and at least the physical (PCS) and mental (MCS) component summary scores of the Short Form Health Questionnaire 36 (SF-36) [4]. Sections of the HAQ dependent on morning stiffness, i.e., dressing, grooming, rising and reaching, are more responsive to change and better reflect disease activity in PMR than other components of the instrument [36]. Euro-Qol and WHOQOL have not been assessed for routine clinical use in PMR. From the laboratory perspective, it can be anticipated that new biomarkers or patterns of biomarkers such as fibrinogen, interleukin-6 and other cytokines will support diagnostic and treatment quality to avoid high doses of GCs in the future.
Discussion: strategies for improving efficiency and efficacy in the care of PMR There is general consensus that most patients with the “polymyalgia syndrome” would merit early referral to the rheumatologist for advice on diagnosis and management. Referrals should be especially considered for treatment dilemmas, atypical features or features that increase likelihood of a non-PMR diagnosis. Besides, ongoing monitoring should then include disease activity based on symptoms, emergence of alternative diagnoses and adverse effects [5]. Pursuit of this strategy will improve patient safety as well as reduce cost of investigations and visits to the healthcare provider. An individualized care plan should be agreed upon with the patient that emphasizes both education and self-assessment. Another point to consider for improvement of efficiency and efficacy in PMR is what strategies should be used to best collect patient data in clinical practice, especially in the follow-up practice. In many cases, the efficiency of healthcare delivery can be increased by the assistance of nurses and other midlevel providers who can follow treatment algorithms and perform standardized assessments of disease activity, enhancing physician availability for management of complex problems. In summary, strategies useful in the care of PMR include: • Using core inclusion criteria (bilateral proximal pain and stiffness) as the first step in a staged process to diagnose PMR (as outlined in Table 1). • Early referral to a specialist from a primary care provider is recommended for patients with atypical features or features that increase the likelihood of a non-PMR diagnosis such as:
• • • • •
Younger patient
