SUMMARY
Polymyalgia rheumatica (PMR) is one of the most common rheumatic inflammatory disorders in people aged over 50. It is characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdles and neck. To date there are no specific diagnostic tests, and in clinical practice the diagnosis of PMR remains based on its characteristic clinical manifestations, laboratory evidence of systemic inflammation, rapid response to low doses of glucocorticoids and exclusion of other disorders that may present with proximal pain and stiffness.
For classification purposes, several criteria have been proposed over time based on retrospective clinical series, but none have been validated and received universal acceptance. Recently, an international collaborative initia- tive between the EULAR and the ACR was undertaken to develop new polymyalgia rheumatica classification criteria. In this review, the provisional 2012 EULAR/ACR classification criteria will be presented and their contribution for the diagnosis of polymyalgia rheumatica will be discussed.
Key words: Polymyalgia rheumatica; Classification criteria.
Reumatismo, 2018; 70 (1): 18-22
n THE NEW 2012 EULAR/ACR CLASSIFICATION CRITERIA
Polymyalgia rheumatica (PMR) is an inflammatory disorder of unknown cause characterized by aching and pro- longed morning stiffness in the shoulder, pelvic girdles and neck, affecting people aged over 50. It is one of the most com- mon inflammatory rheumatic conditions in Caucasian people aged over 50 and its incidence increases with advancing age, peaking between 70 and 80 years of age.
A well-known association exists between PMR and giant cell arteritis (GCA), a large vessel vasculitis that affects the aorta and its branches (1). Controversy exists as to whether PMR represents a single entity disease or is an umbrella term that com- prises a clinical presentation common to a range of related conditions (polymyalgic syndrome) (2). To date there are no specific diagnostic tests, and in clinical practice the diagnosis of PMR remains based on its
characteristic clinical manifestations, labo- ratory evidence of systemic inflammation, rapid response to low doses of glucocor- ticoids (GCs) and exclusion of other dis- orders that may present with polymyalgic syndrome (proximal pain and stiffness).
Ultrasonographic findings of peri-articular inflammation lend further support to the di- agnosis of PMR (3).
Many features of PMR may predispose the unwary clinician to diagnostic error. The main symptoms of PMR, such as proxi- mal pain and stiffness syndrome, systemic symptoms, distal musculoskeletal mani- festation and evidence of systemic inflam- mation, can occur in many other illnesses.
Furthermore, the use of a response to GC therapy to confirm the diagnosis of PMR has several limitations, since GCs are po- tent anti-inflammatory agents that can mask symptoms of other serious condi- tions, especially if used in high doses and for protracted periods. Early differentiation between PMR and late onset rheumatoid
Corresponding author:
Pierluigi Macchioni Department of Rheumatology, Azienda USL-IRCCS di Reggio Emilia, viale Risorgimento 80, 42123 Reggio Emilia, Italy E-mail: pierluigi.macchioni@ausl.re.it
Contribution of the new 2012 EULAR/ACR classification criteria for the diagnosis
of polymyalgia rheumatica
F. Muratore1,2, C. Salvarani1,2, P. Macchioni1
1Division of Rheumatology, Azienda USL-IRCCS di Reggio Emilia;
2University of Modena and Reggio Emilia, Italy
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view, the provisional 2012 EULAR/ACR classification criteria will be presented and their
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view, the provisional 2012 EULAR/ACR classification criteria will be presented and their contribution for the diagnosis of polymyalgia rheumatica will be discussed.
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contribution for the diagnosis of polymyalgia rheumatica will be discussed.
Polymyalgia rheumatica; Classification criteria.
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Polymyalgia rheumatica; Classification criteria.
THE NEW 2012 EULAR/ACR
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THE NEW 2012 EULAR/ACR CLASSIFICATION CRITERIA
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CLASSIFICATION CRITERIA
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olymyalgia rheumatica (PMR) is an
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olymyalgia rheumatica (PMR) is an inflammatory disorder of unknown
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inflammatory disorder of unknown cause characterized by aching and pro
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cause characterized by aching and pro longed morning stiffness in the shoulder,
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longed morning stiffness in the shoulder, pelvic girdles and neck, affecting people
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pelvic girdles and neck, affecting people
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For classification purposes, several criteria have been proposed over time based on retrospective clinical series,
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For classification purposes, several criteria have been proposed over time based on retrospective clinical series, but none have been validated and received universal acceptance. Recently, an international collaborative initia but none have been validated and received universal acceptance. Recently, an international collaborative initia
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tive between the EULAR and the ACR was undertaken to develop new polymyalgia rheumatica classification
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tive between the EULAR and the ACR was undertaken to develop new polymyalgia rheumatica classification view, the provisional 2012 EULAR/ACR classification criteria will be presented and their
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view, the provisional 2012 EULAR/ACR classification criteria will be presented and their contribution for the diagnosis of polymyalgia rheumatica will be discussed.
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contribution for the diagnosis of polymyalgia rheumatica will be discussed.
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Polymyalgia rheumatica (PMR) is one of the most common rheumatic inflammatory disorders in people aged
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Polymyalgia rheumatica (PMR) is one of the most common rheumatic inflammatory disorders in people aged over 50. It is characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdles and
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over 50. It is characterized by aching and prolonged morning stiffness in the shoulder and pelvic girdles and neck. To date there are no specific diagnostic tests, and in clinical practice the diagnosis of PMR remains based neck. To date there are no specific diagnostic tests, and in clinical practice the diagnosis of PMR remains based
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on its characteristic clinical manifestations, laboratory evidence of systemic inflammation, rapid response to
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on its characteristic clinical manifestations, laboratory evidence of systemic inflammation, rapid response to low doses of glucocorticoids and exclusion of other disorders that may present with proximal pain and stiffness.
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low doses of glucocorticoids and exclusion of other disorders that may present with proximal pain and stiffness.
For classification purposes, several criteria have been proposed over time based on retrospective clinical series,
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For classification purposes, several criteria have been proposed over time based on retrospective clinical series,
arthritis (LORA) with PMR-like onset can be difficult because these conditions may have similar clinical presentation (4). Fol- low-up is often needed to establish the cor- rect diagnosis, and in up to 30% of patients initially diagnosed as PMR, the disease is eventually reclassified as LORA (5).
The International PMR Classification Cri- teria Group endorsed by ACR and EULAR has agreed an approach for the polymy- algic syndrome that sees the diagnosis of PMR as a step-wise process (6, 7):
1. evaluate for core inclusion criteria: age over 50; bilateral shoulder and/or pelvic girdle aching; morning stiffness dura- tion longer than 45 min; evidence of an acute-phase response;
2. evaluate for exclusion criteria: exclude mimicking conditions that cannot coex- ist with and rule out the diagnosis of PMR;
3. evaluate a standardized response to GCs (15 mg/day of prednisolone or its equivalent): response is defined as a patient-reported global improvement of 70% within a week of commencing GCs and normalization of inflamma- tory markers within 4 weeks. A lesser response should encourage the search for an alternative condition;
4. confirmation of the diagnosis on follow- up: evaluate response to GCs and ex- clude mimicking conditions during the follow-up.
For classification purposes, several crite- ria have been proposed over time based on retrospective clinical series (Table I) (8- 11). However, none of these criteria have been validated and received universal ac- ceptance. Most of these classification cri- teria include an age cutoff, the presence of shoulder and hip girdle pain and morning stiffness, duration of symptoms lasting more than 2-4 weeks, elevated markers of inflammation and the exclusion of other di- agnoses. Furthermore, some of these clas- sification criteria include a rapid response to GC therapy (9, 11). However, the use of a rapid and dramatic response to GC ther- apy to confirm the diagnosis of PMR has limitations. Several recent studies have in- deed shown that about one third of patients
with PMR treated with GCs according to a standard protocol do not have a complete response even after 3 to 4 weeks of treat- ment (12-14). One of the major unresolved issues is the lack of laboratory and/or im- aging tests that allow early differentiation between PMR and other inflammatory rheumatic diseases, particularly from RA.
Regarding this, preliminary studies have shown that musculoskeletal ultrasound of the shoulders and hips, and antibodies to cyclic citrullinated peptides, can differenti- ate PMR from RA with high specificity and acceptable sensitivity (15-18).
The lack of standardized classification criteria has been a major factor hamper- ing the development of rational therapeu-
Table I - Proposed diagnostic criteria for polymyalgia rheumatica.
Chuang et al. (8)
The presence of all these criteria defines PMR diagnosis:
1. Patients 50 years or older
2. Bilateral aching and stiffness persisting for one month or more involving two of the following areas: neck or torso, shoulders or proximal regions of the arms, and hips or proximal aspects of the thighs
3. Erythrocyte sedimentation rate greater than 40 mm/1st hour 4. Exclusion of other diagnoses except giant cell arteritis Healey (9)
The diagnosis of PMR is made if all these criteria are satisfied:
1. Persistent pain (for at least one month) involving two of the following areas:
neck, shoulders, and pelvic girdle 2. Morning stiffness lasting more than 1 h
3. Rapid response to prednisone (20 mg/day or less)
4. Absence of other diseases capable of causing the musculoskeletal symptoms 5. Age over 50 years
6. Erythrocyte sedimentation rate greater than 40 mm/1st hour Bird et al. (10)
A diagnosis of probable PMR is made if any 3 or more of these criteria are fulfilled:
1. Bilateral shoulder pain and/or stiffness 2. Onset of illness within two weeks
3. Initial erythrocyte sedimentation rate higher than 40 mm/1st hour 4. Morning stiffness exceeding 1 h
5. Age over 65 years
6. Depression and/or loss of weight 7. Bilateral upper arm tenderness
The presence of any 3 or more criteria yields a sensitivity of 92% and a specificity of 80%
Jones and Hazleman (11)
Diagnosis of polymyalgia rheumatica requires presence of all the following:
1. Shoulder and pelvic girdle pain, mainly muscular but without muscle weakness 2. Duration of symptoms at least 2 months
3. Morning stiffness
4. ESR >30 mm/h or C-reactive protein >57.14 nmol/L (6 mg/L)
5. Absence of rheumatoid factor, inflammatory arthritis, and malignant disease 6. Absence of objective signs of muscle disease
7. Prompt and pronounced response to glucocorticoids
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tory markers within 4 weeks. A lesser
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tory markers within 4 weeks. A lesser response should encourage the search
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response should encourage the search gnosis on follow-
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gnosis on follow- : evaluate response to GCs and ex
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: evaluate response to GCs and ex clude mimicking conditions during the
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clude mimicking conditions during the
For classification purposes, several crite
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For classification purposes, several crite
ria have been proposed over time based on
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ria have been proposed over time based on
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The presence of all these criteria defines PMR diagnosis:
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The presence of all these criteria defines PMR diagnosis:
Patients 50 years or older
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Patients 50 years or older Bilateral aching and stif
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Bilateral aching and stif
the following areas: neck or torso, shoulders or proximal regions of the arms,
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the following areas: neck or torso, shoulders or proximal regions of the arms, and hips or proximal aspects of the thighs
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and hips or proximal aspects of the thighs Erythr
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Erythrocyte sedimentation rate greater than 40 mm/1
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ocyte sedimentation rate greater than 40 mm/1 4.
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4. Exclusion of other diagnoses except giant cell arteritis
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Exclusion of other diagnoses except giant cell arteritis Healey (9)
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Healey (9)
The diagnosis of PMR is made if all these criteria ar
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The diagnosis of PMR is made if all these criteria ar 1.
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1.
- Proposed diagnostic criteria for polymyalgia rheumatica.
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- Proposed diagnostic criteria for polymyalgia rheumatica.
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The presence of all these criteria defines PMR diagnosis:
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The presence of all these criteria defines PMR diagnosis:
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The lack of standardized classification
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The lack of standardized classification criteria has been a major factor hamper criteria has been a major factor hamper
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ing the development of rational therapeu
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ing the development of rational therapeu
tic approaches and causing difficulties in evaluating patients in clinical studies. To overcome these limitations, an interna- tional collaborative initiative between the EULAR and the ACR was undertaken to develop new PMR classification criteria (12, 13). These criteria were generated by a prospective evaluation of a cohort of 125 patients with new-onset PMR and 169 sub- jects aged over 50 with new-onset bilateral shoulder pain secondary to conditions po- tentially mimicking PMR. Musculoskeletal ultrasound of the shoulders and hips was done in both groups at baseline and at 26 weeks. The investigators then developed a scoring algorithm (Table II) (12, 13). In patients aged 50 years or older presenting with bilateral shoulder aching and raised inflammatory markers (ESR and/or CRP), a score of clinical criteria ≥4 had a sensi- tivity of 68% and specificity of 78% for discriminating polymyalgia rheumatica from control patients. The specificity was higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for discriminating RA from PMR. The use of ultrasound was discretionary; when ultra- sonography findings consistent with PMR were considered, sensitivity decreased to 66%, but specificity increased to 81%.
Again, the specificity was higher (89%) for discriminating shoulder conditions from PMR and lower (70%) for discriminating RA from PMR (12, 13). Therefore, ultra- sound findings were useful in discriminat-
ing PMR from shoulder conditions, but less so in discriminating PMR from RA. How- ever, ultrasound findings had no effect on the sensitivity of the novel EULAR/ACR criteria for PMR (12, 13, 19).
To date only two studies have assessed the performance of the new 2012 provisional EULAR/ACR PMR clinical classification criteria in discriminating PMR from other mimicking conditions compared with the previous published classification criteria, reporting conflicting results (20, 21).
In a single-center retrospective study (20), our group compared the performance of the published classification/diagnostic cri- teria for PMR, including the new EULAR/
ACR provisional criteria, in 136 PMR pa- tients and 149 controls (including 94 with rheumatoid arthritis), all prospectively followed up according to a standardized protocol that included ultrasound examina- tion of shoulders and hips. The most sen- sitive criteria were the new EULAR/ACR provisional classification criteria (92.6%).
Adding ultrasound, specificity increased from 81.5% to 91.3% when all compara- tors were considered and from 79.7% to 89.9% when only rheumatoid arthritis pa- tients were considered. Bird criteria had a sensitivity of 89.2% but the lowest speci- ficity (40.2% in total cases and 72.5% in RA). Jones and Nobunaga criteria were the most specific criteria (96.7% and 97.8% in total cases and 98.6% and 99.5% in RA) but the less sensitive (63.1% and 58.2%).
Table II - European League Against Rheumatism and American College of Rheumatology provisional cri- teria for classification of polymyalgia rheumatica.
Required criteria: age 50 years or older, bilateral shoulder aching and abnormal C-reactive protein and/or erythrocyte sedimentation rate
Clinical criteria for scoring algorithm:*
1. Morning stiffness lasting more than 45 min 2. Hip pain or restricted range of motion
3. Absence of rheumatoid factor and antibody to cyclic citrullinated peptide 4. Absence of other joint involvement
2 points 1 point 2 points 1 point Ultrasound criteria for scoring algorithm:*
5a. At least one shoulder with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis;
and at least one hip with synovitis or trochanteric bursitis
5b. Both shoulders with subdeltoid bursitis, biceps tenosynovitis, or glenohumeral synovitis
1 point 1 point
*With only clinical criteria, a score of ≥4 had a sensitivity of 68% and specificity of 78% for discriminating polymyalgia rheumatica from comparison patients. With a combination of clinical criteria and ultrasound criteria, a score of ≥5 had a sensitivity of 66% and specificity of 81% for discriminating patients with the disorder from comparison patients.
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tivity of 68% and specificity of 78% for
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tivity of 68% and specificity of 78% for discriminating polymyalgia rheumatica
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discriminating polymyalgia rheumatica from control patients. The specificity was
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from control patients. The specificity was higher (88%) for discriminating shoulder
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higher (88%) for discriminating shoulder conditions from PMR and lower (65%) for
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conditions from PMR and lower (65%) for discriminating RA from PMR. The use of
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discriminating RA from PMR. The use of ultrasound was discretionary; when ultra
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ultrasound was discretionary; when ultra sonography findings consistent with PMR
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sonography findings consistent with PMR were considered, sensitivity decreased
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were considered, sensitivity decreased to 66%, but specificity increased to 81%.
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to 66%, but specificity increased to 81%.
Again, the specificity was higher (89%) for
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Again, the specificity was higher (89%) for discriminating shoulder conditions from
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discriminating shoulder conditions from PMR and lower (70%) for discriminating
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PMR and lower (70%) for discriminating RA from PMR (12, 13). Therefore, ultra
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RA from PMR (12, 13). Therefore, ultra sound findings were useful in discriminat
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sound findings were useful in discriminat
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tivity of 68% and specificity of 78% for
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tivity of 68% and specificity of 78% for
tients and 149 controls (including 94 with
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tients and 149 controls (including 94 with rheumatoid arthritis), all prospectively
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rheumatoid arthritis), all prospectively followed up according to a standardizeduse
followed up according to a standardized protocol that included ultrasound examinause
protocol that included ultrasound examina tion of shoulders and hips. The most senuse
tion of shoulders and hips. The most senonly
our group compared the performance of
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our group compared the performance of
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the published classification/diagnostic cri
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the published classification/diagnostic cri teria for PMR, including the new EULAR/
teria for PMR, including the new EULAR/
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ACR provisional criteria, in 136 PMR pa
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ACR provisional criteria, in 136 PMR pa tients and 149 controls (including 94 with
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tients and 149 controls (including 94 with rheumatoid arthritis), all prospectively
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rheumatoid arthritis), all prospectively
Healey and Chuang criteria had similar intermediate sensitivity (80.3% and 77%) and specificity (81.5% in total cases and 78.3% in RA). A more recent prospec- tive multicenter study assessed the perfor- mance of the published classification/diag- nostic criteria for PMR, including the new EULAR/ACR provisional criteria, in 275 patients with new-onset bilateral shoulder pain (21). At baseline evaluation, 145 pa- tients (52.7%) were diagnosed as PMR and 130 (47.3%) as non-PMR. At the end of the 1-year follow-up, 133 patients (48.4%) were diagnosed with PMR and 142 (51.6%) were diagnosed as non-PMR (including 69 with RA). The 2012 EULAR/ACR clini- cal criteria for PMR had a sensitivity of 89.5% and a specificity of 57.7% when tested against all non-PMR cases. Com- pared with these new classification criteria, only the Bird criteria had higher sensitiv- ity (94%), with lower specificity (50%).
However, the specificities of the other cri- teria sets were significantly higher than the new 2012 EULAR/ACR clinical criteria, ranging from 83%-93%. The Jones crite- ria and the Chuang criteria had the high- est specificities (93.7% and 88%, respec- tively). Surprisingly, when the new 2012 EULAR/ACR clinical criteria for PMR were tested against the 69 RA cases, speci- ficity increased to 66.7%. Shoulder and hip ultrasound were performed only in a sub- group of 48 patients. With the use of the ultrasonography criteria, the sensitivity of the 2012 EULAR/ACR criteria increased to 91.3% but the specificity decreased to 52% for discriminating non-PMR condi- tions from PMR and 53.8% for discrimi- nating RA from PMR. This unexpected finding of Ozen’s study is in disagreement with both the original study and the study by Macchioni, et al, which showed more specificity than sensitivity and a better performance when the criteria were used to discriminate between PMR and non- inflammatory shoulder diseases rather than between PMR and RA. This observation is surprising, because late-onset RA is unani- mously considered the most challenging differential diagnosis. It is difficult to find substantial methodological differences be-
tween the three studies that could explain the different results obtained. Differences in the study design and in the criteria used to include patients and controls and the clinician’s ability to make a diagnosis and perform ultrasonography could, at least in part, explain the different results obtained (22). Prospective, multicenter studies re- cruiting a larger number of controls with arthritis and other conditions mimicking PMR are required.
In conclusion, PMR is one of the most common inflammatory conditions in pa- tients aged over 50. Various criteria have been proposed for the classification of the disease, but in clinical practice the diagno- sis remains only clinical. Imaging modali- ties may support the clinical diagnosis of PMR, and US has been shown to slightly improve the specificity of the diagnosis.
The ACR/EULAR criteria seem to consti- tute progress in the classification of PMR, although they are provisional and need to be validated in further prospective studies and different settings. Furthermore, these criteria are meant for classification and not for diagnostic purposes, have not been test- ed as diagnostic criteria, and can only be applied to patients in whom an alternative diagnosis responsible for the shoulder pain has already been excluded.
Conflict of interest: the authors declare no conflict of interest.
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The ACR/EULAR criteria seem to consti
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The ACR/EULAR criteria seem to consti tute progress in the classification of PMR,
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although they are provisional and need to be validated in further prospective studies
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improve the specificity of the diagnosis.
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The ACR/EULAR criteria seem to consti
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visional classification criteria for
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visional classification criteria for polymyalgia rheumatica: a European League
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Cantini F
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