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Polymyalgia rheumatica
Georgina Espígol-Frigolé, Christian Dejaco, Sarah L Mackie, Carlo Salvarani, Eric L Matteson, Maria C Cid

Polymyalgia rheumatica is an inflammatory disease producing pain and stiffness, mainly in the shoulders and pelvic Lancet 2023; 402: 1459–72
girdle, in people older than 50 years. Elevation of acute phase reactants is common due to the inflammatory nature of Published Online
the disease. Since there are no specific diagnostic tests, diagnosis requires the exclusion of other diseases with similar October 10, 2023
https://doi.org/10.1016/
presentations. Imaging has helped to identify the pathological substrate of polymyalgia rheumatica and it is
S0140-6736(23)01310-7
increasingly used to support clinical diagnosis or to detect coexistent giant cell arteritis. Although polymyalgia
Department of Autoimmune
rheumatica does not clearly impair survival or organ function, it can have a detrimental effect on quality of life. Diseases, Hospital Clínic de
Glucocorticoids at 12·5–25·0 mg prednisone per day are effective in inducing remission in most individuals but, Barcelona, Barcelona, Spain
when tapered, relapses occur in 40–60% of those affected and side-effects are common. Assessment of disease activity (G Espígol-Frigolé MD,
Prof M C Cid MD); Department
can be difficult because pain related to common comorbidities such as osteoarthritis and tendinopathies, can return
of Medicine, University of
when glucocorticoids are reduced, and acute phase reactants are increased less during flares in individuals undergoing Barcelona, Barcelona, Spain
treatment or might increase for other reasons. The role of imaging in assessing disease activity is not yet completely (G Espígol-Frigolé, Prof M C Cid);
defined. In the search for more efficient and safer therapies, tocilizumab and sarilumab have shown efficacy in Institut d’Investigacions
Biomèdiques August Pi i
randomised controlled trials and additional targeted therapies are emerging. However, judicious risk–benefit balance
Sunyer (IDIBAPS), Barcelona,
is essential in applying therapeutic innovations to people with polymyalgia rheumatica. Spain (G Espígol-Frigolé,
Prof M C Cid); Department of
Introduction rheumatica is about three times more common than Rheumatology, Medical
University Graz, Graz, Austria
Polymyalgia rheumatica is a chronic inflammatory giant cell arteritis and about 75% of people with the (C Dejaco MD); Department of
disease involving the periarticular structures of the condition are women.4 Almost all people with polymyalgia Rheumatology, Hospital of
proximal joints almost exclusively in individuals older rheumatica are older than 50 years, and the prevalence of Brunico (SABES-ASDAA),
than 50 years. Polymyalgia rheumatica is clinically the disease is highest among people aged 70–80 years.4 Teaching Hospital of the
Paracelsus Medical University,
characterised by pain and stiffness in the neck, shoulders, As with giant cell arteritis, there is a north–south gradient Brunico, Italy (C Dejaco); Leeds
and pelvic girdle along with systemic symptoms and in the northern hemisphere, with the highest incidence, Institute of Rheumatic and
elevation of acute phase reactants.1,2 Diagnosis and ranging from 41 to 113 cases per 100 000 people aged Musculoskeletal Medicine,
classification of polymyalgia rheumatica is mainly based 50 years and older, in Scandinavia.5 The reason for this University of Leeds, Leeds, UK
(S L Mackie MD); Leeds
on clinical grounds and requires careful evaluation to distribution is unknown but genetic and environmental Biomedical Research Centre,
exclude other diseases. Several imaging modalities can factors might contribute. Differences in reported Leeds Teaching Hospitals NHS
be increasingly useful to clinicians during the diagnostic incidences can also be confounded by socioeconomic Trust, Leeds, UK (S L Mackie);
process.3 Glucocorticoids in the medium-dose range are factors. A population-based study from Olmsted County, Division of Rheumatology,
Azienda USL-IRCCS di Reggio
still the mainstay of treatment since the efficacy of Emilia, Reggio Emilia, Italy
immunosuppressive drugs as glucocorticoid-sparing (C Salvarani MD); Azienda
agents remains controversial.1–3 Trials published in the Search strategy and selection criteria Ospedaliera-Universitaria di
past couple of years indicate that targeted therapies will Modena, University of Modena
We searched PubMed for articles published in English from and Reggio Emilia, Reggio
soon expand the therapeutic horizon for people with database inception to May 31, 2023, using the term Emilia, Italy (C Salvarani);
polymyalgia rheumatica. Disease activity and remission “polymyalgia rheumatica” AND “epidemology”, Division of Rheumatology,
are still difficult to assess because comorbidities, “pathophysiology”, “pathogenesis”, “clinical symptoms”,
Mayo Clinic College of Medicine
and Science, Rochester, MN,
common in older adults, can produce mimicking “clinical findings”, “laboratory findings”, “blood test”, USA (Prof E L Matteson MD)
symptoms. Although polymyalgia rheumatica is not in “abnormalities”, “diagnosis”, “classification”, “imaging”, “giant- Correspondence to:
itself a life-threatening disease or destructive condition cell arteritis”, “immune mediated diseases”, “autoimmune Prof Maria C Cid, Department of
leading to irreversible joint or organ damage, side-effects diseases”, “treatment”, “glucocorticoids”, “immunosuppressive Autoimmune Diseases, Hospital
from chronic glucocorticoid treatment are common in drugs”, “biologic agents”, “targeted therapies”, “disease
Clínic de Barcelona,
these individuals.3 Barcelona 08036, Spain
activity”, “relapses”, or “outcome measures”. Special emphasis mccid@clinic.cat
This Seminar aims to provide an updated general was invested in articles published in the past 5 years, but some
overview of polymyalgia rheumatica, with special focus relevant older publications highly regarded or not completely
on consolidated aspects of the underlined points and on covered by more recent publications were also included.
advances made over the past 5 years. Reference lists of papers were also considered. Articles judged
more relevant to the topics covered were selected by the
Epidemiology authors. Among those, randomised controlled trials,
Polymyalgia rheumatica is among the most common prospective studies, or studies with a larger population sample
inflammatory rheumatic diseases in older adults (aged size than similar studies were preferred. Originality and clarity
≥ 50 years). The epidemiology of polymyalgia rheumatica were also considered. Due to space limitations, some relevant
is difficult to investigate because of the absence of contributions had to be omitted. Abstracts were not included
specific diagnostic tests, and the overlapping spectrum of in the main text.
the disease with giant cell arteritis. However, polymyalgia

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MN, USA reported an incidence of 63·9 cases per 100 000
per year and a prevalence of 701 cases per 100 000 people
older than 50 years.4 A much lower incidence is detected
in southern Europe with an incidence rate of
13 cases per 100 000 per year reported in Italy6 and
13·52 cases per 100 000 per year in Spain.7 A study from
Buenos Aires in Argentina, discloses an incidence and
prevalence similar to Europe8 and the incidence of
polymyalgia rheumatica in South Korea has been
reported as 2·06 cases per 100 000, with a prevalence of
8·21 cases per 100 000 in 2012.9 Polymyalgia rheumatica
does not clearly affect life expectancy.10,11
Pathophysiology
The pathogenesis of polymyalgia rheumatica is incom­
pletely understood (figure 1). Polymyalgia rheumatica
shares demographic and peripheral blood abnormalities
with giant cell arteritis, suggesting common pathogenic
mechanisms eventually targeting different tissues
(eg, synovial structures, arteries, or both). Immuno­
pathologic studies are much more abundant in giant cell
arteritis than in polymyalgia rheumatica due to the easy
availability of tissue (via temporal artery biopsy),
commonly obtained for diagnosis. Consequently, some
pathogenetic principles of giant cell arteritis are frequently
extrapolated to polymyalgia rheumatica. It is assumed that
ageing, genetics, and innate and adaptive immune
mechanisms against unknown triggers play a role.20,21 The
influence of ageing, supported by polymyalgia rheumatica
demography, has been scarcely investigated. Increased
numbers of immunosenescent, autoreactive cells have
been detected in peripheral blood from people with
polymyalgia rheumatica or with giant cell arteritis.22
Abnormalities in innate immune response have been also
reported and include altered pattern of toll-like receptor
expression in peripheral blood mononuclear cells,23,24
neutrophil activation,12 and phagocyte dysfunction.24 Like
giant cell arteritis, polymyalgia rheumatica risk is
increased in individuals carrying HLA-DRB1.04 or
HLA-DRB1.01 alleles,25–27 supporting the role of adaptive
immune mechanisms in its pathogenesis. However, this
association has been less consistent than in giant cell
arteritis, possibly because the classification of polymyalgia
rheumatica relies on clinical assessment with no specific
tests and polymyalgia rheumatica cohorts can be
heterogeneous.
As with giant cell arteritis, most people with active
polymyalgia rheumatica have a remarkable acute phase
response, increased production of IL-6 by circulating
monocytes, and elevated serum concentrations of

Peripheral blood compartment Tissue

Th17 compartment
Subacromial
cytokines bursa

Monocytes Th17
IL-6 lymphocyte

Macrophages

GM-CSF
Tc1
lymphocyte

IL-6 IFN-γ
IFN-γ
Activated
neutrophil Adhesion
molecule
Decrease in
regulatory T cells and in
Th1 CD8+ T lymphocytes* IFN-γ
lymphocyte and B lymphocytes* Th17
lymphocyte? Neovessels

Autoreactive
T cells Th1
lymphocyte

Figure 1: Pathophysiological clues derived from immunopathological studies in polymyalgia rheumatica

Clues to polymyalgia rheumatica pathogenesis are derived from observational studies performed with peripheral blood, synovial fluid, and synovial tissue. The left
panel shows changes identified by several authors in the distribution of cell subsets in peripheral blood, indicating neutrophil activation,12 an increase in Th1 and Th17
lymphocytes, and a decrease in B lymphocytes and regulatory T lymphocytes.13–15 Increased IL-6 concentrations might drive the systemic inflammatory response
typically found in most patients. In synovial tissue (right panel), expression of cytokines related to myeloid cell activation (ie, GM-CSF), Th1 (ie, IFNg) and Th17
differentiation (ie, IL-6) have been observed.16,17 Macrophages are also present, as well as neovessels expressing adhesion molecules that could contribute to
additional inflammatory cell recruitment.16–19 GM-CSF=granulocyte-macrophage colony-stimulating factor. Tc1=T-cytotoxic-type 1 cell. Th1=T-helper-type 1 cell.
Th17= T-helper-type 17 cell. *Changes in CD8+ lymphocytes remain controversial.

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IL-6.28–30 Other abnormalities detected in peripheral blood
include a decrease in CD8+ T lymphocytes and
B lymphocytes, an increase in T lymphocytes producing
T-helper-type 1 (Th1) and 17 (Th17) cytokines, and a
decrease in regulatory T cells.13–15 These changes are
usually less prominent than in giant cell arteritis.13–15
Tissue studies are scarce16–19 but, as with giant cell
arteritis, recent observational immuno­ pathological
studies have shown expression of cytokines related to
Th1 and Th17 pathways in involved tissue (figure 1).16,17
Clinical manifestations
Polymyalgia rheumatica is clinically characterised by
aching and stiffness in the neck, torso, shoulders, and
pelvic girdle, the so called polymyalgic syndrome.31 The
onset is often sudden, but full clinical features can take
several days to develop. Stiffness can predominate in the
morning but can extend to the entire day and aching
interferes with night sleep. Bilateral shoulder pain
radiating distally towards the elbows is the most common
manifestation in most people with polymyalgia
rheumatica (70–95%), whereas neck and hip girdle pain
are less frequent (50–70%).1,31,32 Pelvic girdle pain is
reported along the groin and lateral aspects of the hips,
and frequently radiates to the posterior aspect of the
thighs and knees. Although it can begin in one shoulder
or hip, in the vast majority of cases it soon becomes
bilateral.1,31,32 On examination, people with polymyalgia
rheumatica have painful and restricted range of active
and often passive movements of the shoulders and hips,
without detectable proximal joint swelling, and with
tenderness upon compressing the upper part of the
extremities. A typical finding in people with polymyalgia
rheumatica is the inability to actively abduct the
shoulders past 90 degrees. Muscle weakness can be
difficult to explore in symptomatic individuals but is not
a characteristic feature of initial polymyalgia rheumatica.
However, recurrent disease and glucocorticoid treatment
can eventually decrease muscle trophism and strength.
Systemic manifestations such as low-grade fever,
depression, fatigue, anorexia, and weight loss occur in up
to 40% of people with polymyalgia rheumatica.1,31,32 High,
spiking fevers are uncommon in polymyalgia rheumatica
in the absence of giant cell arteritis.1,31,32
About 50% of people with polymyalgia rheumatica
have distal musculoskeletal manifestations.33–35
Specifically, one quarter of individuals with the condition
have pain and swelling in the knees (40%) and
wrists (40%).33–35 Involvement of the metacarpophalangeal
joints is less common, but not exceptional, as
25% of all patients have peripheral arthritis mimicking
other rheumatic diseases.33 In contrast to rheumatoid
arthritis, the arthritis is asymmetric, and non-erosive.
Finally, diffuse distal extremity swelling with pitting
oedema mostly over the dorsum of the hands and wrists,
but also over the ankles and tops of the feet, is seen in
around 8–12% of patients.33,34 This condition, often
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referred to as remitting seronegative symmetric synovitis
with pitting oedema (RS3PE) syndrome, reflects
prominent distal tenosynovitis of the extensor tendons of
hands or feet, variably associated with joint synovitis, and
can be the main reason for the peripheral inflammatory
symptoms and subcutaneous oedema.33,34 However,
RS3PE is not exclusive to polymyalgia rheumatica. Carpal
tunnel syndrome due to tenosynovitis of wrist flexors has
been observed in 14% of patients.33
Laboratory abnormalities
Laboratory findings are non-specific but indicate the
inflammatory nature of polymyalgia rheumatica: elevated
erythrocyte sedimentation rate (ESR) and C-reactive
protein (CRP), normochromic normocytic anaemia,
thrombocytosis, hypoalbuminaemia, elevated fibrinogen
levels, and raised α2 globulin proteins are commonly
detected.1,3 Both ESR and CRP should be requested.
Elevated ESR (at least 40 mm/h) has been included in
all sets of classification criteria for polymyalgia
rheumatica.32,35–40 but a nearly normal ESR does not
completely exclude diagnosis, as low ESR has been
reported in 7–20% of people with polymyalgia
rheumatica.1 CRP is nearly always elevated in untreated
polymyalgia rheumatica, with concentrations greater
than 0·5 mg/dL in 99% of individuals at diagnosis.41,42
Thus, a normal ESR and CRP are infrequent and require
referral to exclude mimicking conditions, as the
diagnosis of polymyalgia rheumatica is unlikely.41,42
Autoantibodies, including antinuclear antibodies, anti-
cyclic citrullinated peptide antibodies and rheumatoid
factor are typically negative; however, in approximately
10% of older adults rheumatoid factor can be non-
specifically positive, usually at low titre.43 These tests are
helpful in patients in whom mimicking inflammatory
rheumatic diseases can be considered (table 1).
Diagnosis and classification
Clinical diagnosis
The diagnosis of polymyalgia rheumatica is based on
clinical grounds and the exclusion of other diseases that
can present with the polymyalgic syndrome (table 1).39,40
Accordingly, the diagnosis of polymyalgia rheumatica
conveys a substantial uncertainty and requires expertise to
avoid overdiagnosis or underdiagnosis.44,45 Rheumatic
(both inflammatory and non-inflammatory) diseases can
present with similar symptoms and are the most common
diseases mimicking polymyalgia rheumatica. Typical
polymyalgia rheumatica manifes­ tations and even
suggestive ultrasound findings can develop in people with
late-onset rheumatoid arthritis.40 Calcium pyrophosphate
deposition disease and—less frequently—spondylo­
arthropathies or late-onset systemic lupus erythematosus
can also present with the polymyalgic syndrome. Other
diseases (ie, malig­nancies, infections, endocrinopathies,
or neurodegenerative disorders) can occasionally mimic
polymyalgia rheumatica. Important clinical clues pointing
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Clinical clues Actions and tests

Step 1: identification of the polymyalgic syndrome
Patient consultation because of aching
Step 2: exclusion of mimicking diseases with appropriate tests or specialist referral
Inflammatory rheumatic diseases with typical joint involvement
Late-onset rheumatoid arthritis
Late-onset spondylarthritis
Late-onset systemic lupus erythematosus
Calcium pyrophosphate deposition disease†
Inflammatory rheumatic diseases with predominant systemic involvement
Inflammatory myopathies
Systemic vasculitis other than giant cell
arteritis
Non-inflammatory rheumatic diseases
Osteoarthritis†
Tendinopathies†
Chronic pain syndromes†
Other
Malignancies (eg, multiple myeloma and
bone metastasis)
Subacute and chronic infections (eg,
endocarditis, septic arthritis)
Neurodegenerative (eg, Parkinson’s disease
and amyotrophic lateral)
Drug-induced myopathy
Endocrinopathies (eg, thyroid disease and
hyperparathyroidism)
Osteomalacia
Step 3: exclusion of giant cell arteritis
People with features that could suggest giant
cell arteritis
Step 4: specialist referral
Diagnostic uncertainty: alternative diagnosis
(same as previous step)
Treatment optimisation for polymyalgia
rheumatica
This table is based on expert opinion. APR=acute phase reactants. CRP=C-reactive protein. dsDNA=double-stranded DNA. ESR=erythrocyte sedimentation rate. *Imaging: x-ray, ultrasound, MRI or PET-CT, as
contextually indicated. †Might coexist with polymyalgia rheumatica. ‡Common comorbidities in older adults (aged ≥50 years) could independently produce mild elevation of these markers (ie, mild infection
and anaemia of any cause).
New onset of pain and stiffness in the upper and sometimes lower
girdles
Symmetrical distal peripheral arthritis and erosions
Inflammatory low-back pain and stiffness, and enthesitis
Systemic manifestations (eg, skin and serositis)
Knee and wrist involvement; dens axis also frequently involved
Weakness and myalgia predominate, no clear stiffness, and systemic
involvement (eg, skin and lung)
Myalgia predominates over stiffness and systemic involvement
(eg, skin; kidney; lung; ear, nose, and throat; and peripheral neuropathy)
Mechanical pain, stiffness, or deformities
Mechanical pain and limited range of motion
Long-lasting, diffuse, non-inflammatory pain without objective clinical
signs and with trigger points and fatigue
Widespread pain and no stiffness; focal manifestations of the primary
tumour; and systemic features
Fever, systemic features, focal manifestations (eg, new heart murmur,
skin lesions, back pain, mono-articular arthritis); marked elevation of
CRP compared with ESR
Gradual onset, stiffness with weakness and muscle atrophy, rather than
pain; other neurological features (eg, gait disturbance, hyperreflexia,
clonus, muscle fibrillation, tremor)
Intake of a potentially myopathic drug (ie, statins); myalgia
and weakness predominate
Weakness more prominent than pain; other features of hyperthyroidism
(eg, tremor, tachycardia, diarrhoea, weight loss) or hypothyroidism
(eg, bradycardia, constipation, weight gain)
Diffuse pain and weakness
Cranial symptoms, extremity claudication, temporal artery
abnormalities, marked systemic symptoms
Age <60 years; chronic onset (>2 months); lack of shoulder involvement; Tests guided by clinical clues; normal or extremely elevated APR
lack of inflammatory stiffness; prominent weakness; marked systemic
features; coexisting, potentially confounding, comorbidities; features
of other rheumatic diseases; suspicion of giant cell arteritis; and
incomplete, poorly sustained, or no response to glucocorticoids
Inability to reduce glucocorticoids due to relapsing disease,
contraindications to glucocorticoids therapy, early glucocorticoids
side-effects, and need for long-term glucocorticoids (>2 years)
Detailed history and examination; ESR and CRP
Anti-cyclic citrullinated peptides, rheumatoid factor; imaging*
Imaging
Antinuclear antibodies, anti-dsDNA, other autoantibodies,
complement
Imaging; synovial fluid examination (presence of crystals)
Creatine kinase, autoantibodies; electromyogram; muscle MRI;
and muscle biopsy
Urinalysis, anti-neutrophil cytoplasmic antibodies detection,
cryoglobulins, complement; electromyogram; imaging; and biopsy
of involved sites
Physical examination; ESR and CRP‡ (not elevated); imaging
Physical examination and imaging
Physical examination and imaging; ESR and CRP‡ (not elevated)
Blood tests guided by clinical assessment: marked elevation of ESR
compared with CRP; hepatic function, LDH, and protein
electrophoresis and immunofixation; tumour markers; and imaging
(PET-CT), endoscopy (to rule out gastrointestinal or lung
malignancies, when contextually indicated), and biopsies
Cultures and serology; procalcitonin; arthrocentesis; imaging,
as guided by clinical assessment
No elevation of ESR and CRP‡; specialist evaluation
Creatine kinase, anti-HMGCR antibodies, and muscle biopsy
in selected cases
APR can be elevated in hyperthyroidism; creatine kinase and
transaminases can be elevated, thyroid-stimulating hormone,
calcium and phosphorous, and parathyroid hormone
Vitamin D; imaging
APR highly elevated or temporal artery biopsy; imaging of cranial
vessels, large-vessel imaging, or both
Differentiating active disease from comorbidities,
immunosuppressive treatment, targeted therapies, and inclusion in
clinical trials

Table 1: Stepwise approach to the diagnosis of polymyalgia rheumatica

towards polymyalgia rheumatica are the presence of weakness, rigidity, constitutional symptoms, or multi-
proximal inflammatory pain and stiffness along with organ involvement are more prominent than pain,
elevation of acute phase reactants. When features such as physicians should be alert to alternative diagnoses, such

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as muscle disorders, neurodegenerative diseases, or Biceps tenosynovitis Subdeltoid bursitis

malignancies (table 1). Conversely, widespread pain or
peripheral joint involvement might suggest metastasis or A B
myeloma or other rheumatic diseases, respectively.
Normal or very high levels of acute phase reactants are not
typical of polymyalgia rheumatica and should prompt
referral for consideration of other diseases. Clinically
guided blood tests and imaging as detailed in table 1 are *
useful for the diagnosis of polymyalgia rheumatica and
exclusion of other conditions. Physicians should be aware
that features of other diseases could also emerge during
follow-up.
C D
Role of imaging
Imaging in its various modalities (eg, ultrasound, MRI,
[¹⁸F]fluorodeoxyglucose [¹⁸FDG]-PET, or ¹⁸FDG-PET-CT
for better anatomic reference) has greatly contributed to
identifying the pathological substrate of polymyalgia
rheumatica. Ultrasound findings increase the specificity
of classification criteria (see next section) and can be
useful in primary care to substantiate findings suggestive
of polymyalgia rheumatica or to detect potentially
confounding diseases such as tendinopathies or crystal
deposition diseases.40 Although there is no specific lesion
for polymyalgia rheumatica, ultrasound and MRI studies
indicate that mild bilateral subacromial or subdeltoid
bursitis occurs in 32–93% of people with the condition.
Furthermore, shoulder capsulitis (69%), rotator cuff
tendonitis (72%), and biceps tenosynovitis (37–60%) are
common findings in untreated individuals with
polymyalgia rheumatica (figure 2).46–49 Bilateral synovitis
of shoulders (26–52%) and hips (18–32%), as well as
peripheral joint involvement, particularly tenosynovitis
of extensor tendons at hands (67%) are also compatible
with a diagnosis of polymyalgia rheumatica,46–49 whereas Figure 2: Characteristic ultrasound and PET-scan imaging findings in people with polymyalgia rheumatica
extensive synovial proliferation or erosions should (A) Cross-sectional view of biceps tenosynovitis. Asterisk denotes the biceps tendon, which is surrounded by
hypoechoic fluid, pointed to by arrows. (B) Longitudinal view of subdeltoid bursitis. Arrows delimitate the hypoechoic
prompt suspicion for another diagnosis, particularly fluid within the bursa. (C) Increased [¹⁸F]fluorodeoxyglucose (¹⁸FDG) uptake by PET scan in the shoulders and
rheumatoid arthritis.48 Bilateral trochanteric bursitis has trochanteric areas (arrows). (D) Increased ¹⁸FDG uptake by PET scan in the cervical and interspinous areas (arrows).
been observed in up to 90% of patients in early imaging
studies,50 whereas later studies only found this lesion in predominant pelvic girdle symptoms.58–60 Peritendinous
about 20% of people with polymyalgia rheumatica.40 and intratendinous contrast enhancement of various
PET can show ¹⁸FDG uptake in the shoulders, tendons (eg, gluteus medius and minimus tendons at the
sternoclavicular joints, hips, ischial tuberosities, and insertion into the major trochanter, rectus femoris tendon
hips.51,52 Another characteristic lesion of polymyalgia at the proximal insertion, and adductor longus origins at
rheumatica is interspinous bursitis of the cervical and the inferomedial pubic symphysis) emerges as the most
lumbar spine, observed using ultrasound, MRI, remarkable abnormality.58,59 Inflammation seems to
or ¹⁸FDG-PET in approximately 50% of patients originate in the peritendineum and secondarily extend to
(figure 2).51,53–55 However, inflammation at that site is only bursae and joints.58,59 Isolated inflammation of joints was
inconsistently associated with neck and lumbar pain or not observed. Another study using MRI and ¹⁸FDG-PET
stiffness.53–55 supported this observation, revealing that ¹⁸FDG uptake at
Scores for PET evaluation have been proposed in the ischial tuberosity corresponded to hamstring
retrospective studies yielding 96·9–98·8% sensitivity peritendonitis rather than to ischial bursitis.61,62
and 92·8–95·2% specificity for the diagnosis of Predominant tendinous involvement was also observed at
polymyalgia rheumatica but need to be validated by the knees.63 Extracapsular inflammation at the pelvis
prospective assessment.56,57 seemed also to better differentiate polymyalgia rheumatica
MRI studies have provided deeper insight into the from late-onset rheumatoid arthritis, while the pattern of
anatomical structures involved in people with inflammation at the shoulders was similar in both

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diseases.60 Although histopathological confirmation would
be necessary to substantiate these observations, these
studies provide novel insights into the anatomical target
of inflammation in polymyalgia rheumatica.
Imaging can also be helpful to uncover coexisting giant
cell arteritis in people with polymyalgia rheumatica.51,64–66
Ultrasound has been more widely used and validated to
detect involvement of cranial and axillary arteries
and ¹⁸FDG-PET to detect large-vessel vasculitis.67–70 The
clinical relevance of systematically screening for
subclinical giant cell arteritis in people with new, typical
polymyalgia rheumatica is unclear.
Classification criteria
Classification criteria are useful for characterising
diseases for investigation purposes, especially for
diseases with no single specific diagnostic features such
as polymyalgia rheumatica. The criteria influence the
assessment of disease epidemiology and the selection of
affected individuals for clinical trials. Classification
criteria aim to include the most typical features of the
disease, which differentiate polymyalgia rheumatica
from other musculoskeletal conditions, mainly late-onset
rheumatoid arthritis and considering these criteria can
also assist physicians in diagnosis.
Various criteria sets based on retrospective medical
record review have been used over the years.32,35–40 In 2012,
the European Alliance of Associations for Rheumatology
(formerly European League Against Rheumatism; EULAR)
and American College of Rheumatology (ACR)
classification criteria for polymyalgia rheumatica were
developed using a prospective longitudinal methodology.
Panel: The European Alliance of Associations for
Rheumatology (formerly European League Against
Rheumatism) and American College of Rheumatology
proposed classification criteria for polymyalgia
rheumatica in 201240
Patients aged 50 years or older with bilateral shoulder aching
and abnormal C-reactive protein concentrations or an
increased erythrocyte sedimentation rate, plus at least
4 points (without ultrasonography) or at least 5 points (with
ultrasonography) from:
• Morning stiffness for more than 45 min (2 points)
• Hip pain or restricted range of motion (1 point)
• Absence of rheumatoid factor or anti-citrullinated
protein antibodies (2 points)
• Absence of other joint involvement (1 point)
• If ultrasonography is available, at least one shoulder with
subdeltoid bursitis, biceps tenosynovitis, or glenohumeral
synovitis (either posterior or axillary), as well as at least
one hip with synovitis or trochanteric bursitis (1 point)
• If ultrasonography is available, both shoulders with
subdeltoid bursitis, biceps tenosynovitis, or glenohumeral
synovitis (1 point)
1464
These criteria highlight the importance of hip involvement
and, unlike late-onset rheumatoid arthritis, the absence of
rheumatoid factor and anti-citrullinated peptide antibodies
(panel).40 Complete response to medium-dose
glucocorticoids—that were included in some previous
criteria—was reached in only 71% of participants and,
conversely, glucocorticoids temporarily alleviated
symptoms of other conditions. Response to glucocorticoid
treatment did not improve sensitivity or specificity and,
consequently, was not included in the final criteria. An
innovation of the EULAR and ACR classification criteria
effort is the use of musculoskeletal sonography of shoulder
and hip girdle structures. Bilateral subacromial or
subdeltoid bursitis and trochanteric bursitis in patients
with inflammatory pain of the shoulder or pelvic girdle is
highly suggestive of polymyalgia rheumatica in the
absence of peripheral joint involvement.40 The sensitivity
of the EULAR and ACR criteria for polymyalgia
rheumatica is 68%, and specificity is 78%, increasing to 81%
with the use of ultrasound, which mostly helps to
distinguish it from degenerative disorders.
Analysis of independent datasets reveals that EULAR
and ACR criteria have the best discriminatory
performance when both sensitivity and specificity are
considered.71 Evaluations of these criteria in other patient
populations disclosed estimates of sensitivity of
85·2–92·6% and specificity of 57·7–81·5%.71–74 Adding
ultrasound, the specificity estimates for these criteria
ranged from 52·0% to 91·3%.71–74 In the EULAR and
ACR study, 8% of people initially classified as having
polymyalgia rheumatica had another diagnosis at
6 months, and 4·7% of controls were reclassified as
polymyalgia rheumatica by the end of follow-up.40
Polymyalgia rheumatica in the context of other
diseases
Giant cell arteritis
Polymyalgia rheumatica and giant cell arteritis might be
part of a disease spectrum.75,76 Approximately 40–60% of
people with biopsy or imaging-proven giant cell arteritis
have polymyalgia rheumatica.1 Polymyalgia rheumatica
might precede clinically apparent giant cell arteritis by
weeks, months, or years; appear simultaneously with giant
cell arteritis; or develop after a self-limiting episode of
cranial symptoms77 or during a relapse, even if polymyalgia
rheumatica manifestations were not present at the time of
giant cell arteritis diagnosis.78,79 The proportion of people
primarily presenting with polymyalgia rheumatica and
found to have asymptomatic giant cell arteritis is more
variable, ranging from 0% to more than 40%.1,51,67–80 The
number depends on selection criteria (ie, how stringently
isolated polymyalgia rheumatica is defined and cranial
symptoms excluded); pre-test suspicion, since not all
people with polymyalgia rheumatica are routinely imaged
or have a biopsy taken to rule out giant cell arteritis; and
how giant cell arteritis is defined (eg, biopsy, imaging, or
classification criteria). Giant cell arteritis might be
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suspected when there are cranial symptoms (which are
sometimes very mild) or temporal artery abnormalities at
physical examination (eg, tenderness, hardness,
asymmetric, and weak or absent pulse) and need to be
confirmed by temporal artery biopsy or vascular imaging.
In the absence of cranial symptoms, giant cell arteritis
might be suspected in people with marked systemic
manifestations, persistently elevated acute phase reactants,
vascular pain in the lower extremities, or incomplete
response to the dose range of glucocorticoids used in
polymyalgia rheumatica (see upcoming sections).65,69,81,82 As
previously mentioned, imaging of large vessels can help to
detect giant cell arteritis in these patients. People
primarily presenting with polymyalgia rheumatica can
subsequently develop cranial symptoms of giant cell
arteritis and are at risk of cranial ischaemic complications
when cranial manifestations of giant cell arteritis appear,
such as headache, visual symptoms, or jaw claudication.77
Patients with polymyalgia rheumatica with no cranial
symptoms in whom large-vessel vasculitis is discovered by
imaging might be at reduced risk of cranial ischaemic
complications.51
Some people with polymyalgia rheumatica could have
minimal periadventitial and vasa vasorum infiltrates
noted on temporal artery biopsy, which are not irrelevant
but are not specific enough to confirm the diagnosis of
giant cell arteritis.83 These features can also appear in
other diseases, including small-vessel vasculitis,
infection, and malignancy.84
Other immune-mediated diseases
Physicians need to be aware that other immune-mediated
diseases can appear in people with polymyalgia
rheumatica. Autoimmune thyroid disease, autoimmune
hepatitis, primary biliary cholangitis, Sjögren’s syndrome,
or inflammatory bowel disease have been reported.85–87
Polymyalgia rheumatica can develop in people
with malignancies treated with immune checkpoint
inhibitors.88–90 The prevalence is low, ranging from less
than 1% to 2·1% of treated patients and reports are scarce,
mainly limited to retrospective studies.88–90 Polymyalgia
rheumatica features in these patients are not always
typical. About 25% of patients in this group do not fulfil
EULAR and ACR classification criteria for polymyalgia
rheumatica and peripheral arthritis or RS3PE is more
frequent than in primary polymyalgia rheumatica. In such
patients, acute phase reactants are less likely to be elevated
and response to glucocorticoids is not always satisfactory,
requiring higher doses or additional treatment.
Methotrexate, hydroxychloroquine, or tocilizumab have
been used to alleviate symptoms in these patients, but
more data are needed on their effectiveness.88–90
Management
Glucocorticoids
Glucocorticoids are the cornerstone of initial treatment.
Current practice is to start with oral prednisone or an
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Seminar
equivalent at a dose of 12·5–25·0 mg per day.91 Within
this recommended range, the dose can be adapted to
bodyweight and possible risk factors for refractory disease
for which an increased dose might be preferred (see next
section).91,92 Conversely, in the context of comorbidities
increasing the risk for glucocorticoid-related adverse
events (ie, diabetes, hypertension, osteoporosis, and
obesity), a reduced initial dose can be chosen.
Response to glucocorticoids is usually rapid—within a
few days to 1 week in most cases. However, in some
patients, response is slower than a week. In a follow-up
study of 85 people with new-onset polymyalgia rheumatica
in whom response was defined as a 70% reduction of
symptoms on the visual analogue scale for patients’ global
assessment, 27% of participants did not completely
respond to standard glucocorticoid therapy after 4 weeks
and 20% did not completely respond after 12 weeks.93
Once remission is achieved, prednisone is reduced to
10 mg per day within 4–8 weeks, and the daily dose
subsequently tapered by approximately 1 mg per day per
month until discontinuation if remission is maintained.
The usual minimum duration of glucocorticoid therapy
is 9–12 months; however, some patients can sustain
remission with shorter treatment periods.94 Longer
treatment is often required when relapses occur. It is not
uncommon for people with polymyalgia rheumatica to
require low-dose glucocorticoid therapy (≤5 mg per day)
for several years, and sometimes treatment is lifelong.95
Glucocorticoids are usually administered as a single dose
in the morning. In cases of severe night pain, the dose
can be split, usually administering a third of the daily
dose in the evening.91
For select patients (eg, those with a low adherence to
oral therapies), an alternative to oral glucocorticoids can
be intramuscular methylprednisolone, usually started at
120 mg every 3 weeks with subsequent dose tapering.91
One randomised trial reported decreased weight gain
and decreased cumulative glucocorticoid dose in the
group receiving intramuscular methylprednisolone
treatment compared with those receiving conventional
oral therapy—efficacy was similar.96
Long-term oral glucocorticoid therapy carries risks of
many potential toxicities across multiple organ systems
(ie, osteoporosis, hypertension, weight gain, diabetes, and
cataracts).97–99 Even low-dose glucocorticoids can increase
cardiovascular risk in the long term100 and studies indicate
that frailty, resulting from persistent inflammation,
reduced physical activity, or chronic glucocorticoid use,
can affect a substantial proportion of these patients.101
Fatigue and depression exemplify the complex and
time-dependent interplay of the effects of inflam­matory
activity and treatment-related adverse effects in
polymyalgia rheumatica.102 Fatigue and depression are
also strongly influenced by contextual factors including
multimorbidity.
Prevention and treatment of glucocorticoid-related
adverse events are crucial aspects of care in polymyalgia
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Seminar
rheumatica.103 Measures include regular monitoring of
blood pressure, serum glucose, and other cardiovascular
risk factors as well as screening and prevention of
osteoporosis, and appropriate calcium and vitamin D
intake. On the basis of fracture risk assessment and
national thresholds for preventive therapy, antiresorptive
therapies should be considered.103 Non-pharmacological
interventions such as exercise, muscle strengthening,
and interaction with support groups when available are
advised to minimise fatigue and depression.91
Broad-spectrum immunosuppressive agents
To avoid relapses and reduce glucocorticoid exposure
and side-effects, several glucocorticoid-sparing agents
have been tried. Among immunosuppressive drugs,
methotrexate has been the most widely studied;
however, results are conflicting.104–107 One trial showed
that methotrexate led to a reduction of relapses
compared with placebo,104 and two trials suggested a
lower cumulative glucocorticoid dose in the
methotrexate group,104,105 whereas other studies were
unable to substantiate these results.106,107 The 2015 EULAR
and ACR recommendations for the management of
polymyalgia rheumatica consider methotrexate for
treatment of patients at high risk of relapse or long-term
glucocorticoid therapy (see next section) as well as those
with risk factors for glucocorticoid-related adverse
events (ie, pre-existing osteoporosis, diabetes,
hypertension, or overweight).91 The methotrexate doses
tested in trials (7·5–10·0 mg oral methotrexate per
week) were cautious and inferior to those frequently
used in clinical practice (up to 25 mg oral or
subcutaneous methotrexate per week). The long-term
follow-up of a clinical trial did not show a reduction of
glucocorticoid-related side-effects after 5 years in
patients receiving oral methotrexate (10 mg per week);
however, this study used a relatively low dose and was
limited by a steady loss of trial participants.107 Although
generally well tolerated, methotrexate is not exempt of
side-effects (eg, nausea, fatigue, leucopenia, infection,
and hair loss) and cannot be used in patients with
reduced kidney function.
Other conventional synthetic immunosuppressants
have been studied for polymyalgia rheumatica, but this
has been rare. Two case series suggested beneficial
effects of leflunomide in people with difficult to treat
polymyalgia rheumatica and giant cell arteritis.108,109 A
randomised, double-blind, placebo controlled, phase 3
trial with leflunomide 20 mg per day or placebo along
with 26-week glucocorticoid tapering is currently
recruiting (NCT03576794). Azathioprine was tested in a
pooled analysis of people with polymyalgia rheumatica
and giant cell arteritis, revealing a reduced mean
prednisone dose after 1 year in the azathioprine group.110
Because of the scarcity of data, these agents are currently
not recommended as first-line treatment for people with
polymyalgia rheumatica.90
1466
Targeted therapies
TNF-α blockers were the first targeted biological agents
tested in polymyalgia rheumatica, but they did not show
any benefit.111,112
The effect of anti-IL6 receptor antibody tocilizumab
has been shown in two published randomised controlled
trials from 2022.113,114 In a phase 2/3 trial, 36 people with
new polymyalgia rheumatica were randomly assigned to
receive either subcutaneous tocilizumab (162 mg per
week) or placebo for 16 weeks (1:1 ratio).113 All participants
received oral prednisone 20 mg, tapered down to 0 mg
over 11 weeks. The primary endpoint, which was
glucocorticoid-free remission at 16 weeks, was reached
by 12 (63%) of 19 people receiving tocilizumab, but only
by 2 (12%) of 17 people receiving placebo. Additionally,
time to first relapse was longer in the intervention group
than in the control group (130 vs 82 days, p=0·007) and
tocilizumab treated participants had a lower cumulative
glucocorticoid dose after 24 weeks than those treated
with the placebo (781 mg vs 1290 mg, p<0·001).113 In a
phase 3 randomised controlled trial evaluating the
efficacy of tocilizumab in relapsing polymyalgia
rheumatica, 101 people with persistent disease activity
(CRP polymyalgia rheumatica activity score >10; see next
section) requiring ≥10 mg prednisone per day, were
randomly assigned to receive tocilizumab (8 mg/kg
every 4 weeks) or placebo.114 The primary efficacy
endpoint, evaluated at 24 weeks, was a CRP–polymyalgia
rheumatica activity score of less than 10 with daily
prednisone of 5 mg or less, or after decreasing daily
prednisone dose by 10 mg or more. This endpoint was
reached by 67% of tocilizumab recipients compared with
31% of participants receiving placebo (p<0·001).114
Overall, these studies indicate that the addition of
tocilizumab to glucocorticoids can be of benefit in
individuals with polymyalgia rheumatica, enabling
faster glucocorticoid tapering and a reduction in
cumulative glucocorticoid dose compared with placebo.
The use of tocilizumab as monotherapy is not clearly
supported by existing evidence.115–117 In these trials,
adverse events were similar in both arms. Adverse events
in patients treated with tocilizumab include elevation
of transaminases, cytopenias, hyperlipidaemia, and
infection.
A phase 3 randomised controlled trial testing the IL-6
receptor blocker sarilumab in individuals with relapsing
or refractory polymyalgia rheumatica was terminated
prematurely due to protracted recruitment exacerbated
by the COVID-19 pandemic, but results from the
recruited and analysed 118 participants favoured
sarilumab over placebo.118 As a result, the US Food and
Drug Administration approved sarilumab in February,
2023, for the treatment of individuals with inadequate
response to glucocorticoids or relapsing polymyalgia
rheumatica.
Although the exact role of B lymphocytes in the
pathogenesis of polymyalgia rheumatica remains elusive
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Seminar

(figure 1),15,16,18 a small randomised controlled trial
from 2021 indicates that B-cell depletion with rituximab
might be effective in people with newly diagnosed or
relapsing polymyalgia rheumatica. 11 (48%) of
23 participants in the rituximab group and five (21%) of 24
in the placebo group had glucocorticoid-free remission
at 21 weeks.119 Larger trials are needed to define the role
of rituximab in the treatment of people with polymyalgia
rheumatica. A small, single-arm trial included 14 people
(three with newly diagnosed polymyalgia rheumatica
and 11 with relapsing polymyalgia rheumatica) who were
treated with 10 mg per day of the JAK inhibitor,
tofacitinib, along with 15 mg prednisone per day with a
standardised tapering. Remission (requiring 2·5 mg
prednisone per day) was reached by 86% of participants
at 24 weeks.120 The efficacy and safety of targeted
therapies needs to be evaluated in large randomised
controlled trials. Additional ongoing clinical trials in
people with polymyalgia rheumatica are summarised in
table 2.
Assessment of disease activity
Appropriate management of people with polymyalgia
rheumatica requires an accurate appraisal of disease
activity to adjust therapy, distinguishing activity from
comorbidities and treatment-related side-effects. An
accurate balance between activity and long-term
treatment toxicity is crucial for patients. A treat-to-target
approach to polymyalgia rheumatica might help to
minimise unnecessary treatment toxicity, but this
depends on accurate assessment of disease activity.121 The
need to improve patient outcomes and the availability of
potential new therapies has prompted efforts to better
define disease activity status and outcomes to be
measured in clinical trials.122
Relapses
Relapse is defined as an increase in polymyalgia
rheumatica activity, usually occurring during
glucocorticoid tapering or discontinuation, and resulting
in re-escalation of therapy. When symptoms recur and a
flare is suspected, detailed clinical evaluation is necessary
to exclude other conditions or reappearance of chronic
pain due to comorbidities (ie, osteoarthritis) and masked
by glucocorticoids. In observational studies, 43% of people
with polymyalgia rheumatica relapsed at least once
within the first year of diagnosis.95 Those who relapsed
during the first 6 months were more likely to require
long-term treatment beyond 2 years.123 Female sex,124,125
peripheral arthritis,33 high levels of ESR and CRP,41,125 and
a combination of low haemoglobin and high serum
levels of soluble IL-6 receptor,126 have been associated
with an elevated relapse rate; these findings, however,
require confirmation. Fast glucocorticoid tapering might
also be associated with relapses.127
Clinical flares are usually associated with a rise in acute
phase reactants. Elevation can be slight during
glucocorticoid therapy,41,42 and even normal in individuals

Rationale Characteristics Population Status Trial number

Baricitinib (JAK1 and Efficacy in other rheumatic diseases; case Multicentre, randomised, double- 34 early onset Recruiting NCT04027101
JAK2 inhibitor) reports in polymyalgia rheumatica; small trial blind, phase 2 trial
with tofacitinib in polymyalgia rheumatica
ABBV-154 (anti-TNF Local delivery of GRM; avoiding systemic Multicentre, randomised, double- 200 relapsing Recruitment NCT04972968
and glucocorticoid- effects of glucocorticoid blind, phase 2 trial Completed
receptor conjugate)*
Abatacept Inhibition of CD28-mediated T-cell activation; Multicentre, randomised, double- 34 early onset Recruiting NCT03632187
efficacy in giant cell arteritis and rheumatoid blind, phase 3 trial
arthritis
Leflunomide Immunosuppressive agent; efficacy in Multicentre, randomised, double- 94 newly Recruiting NCT03576794
rheumatoid arthritis; small series in blind, phase 3 trial diagnosed
polymyalgia rheumatica; observational studies
in giant cell arteritis and polymyalgia
rheumatica
Low-dose IL-2 Stimulation of regulatory T cells to suppress Open label, phase 2 15 Unknown NCT04062006
inflammation
SPI-62† HSD-1 inhibitor, to avoid systemic effects of Non-randomised, single-blind, 48 Recruiting NCT05436652
glucocorticoids phase 2
Rituximab B-cell depletion, efficacy in a small RCT in Randomised, parallel assignment, 114 recently Recruiting NCT05533125
polymyalgia rheumatica phase 3 diagnosed
Rituximab B-cell depletion, efficacy in a small RCT in Randomised, parallel assignment, 174 relapsing Recruiting NCT05533164
polymyalgia rheumatica phase 3
Secukinumab Fully human anti-IL-17A antibody Multicentre, randomised, double- 360 relapsing Recruiting NCT05767034
blind, phase 3
GRM=glucocorticoid receptor modulator. HSD-1= hydroxysteroid dehydrogenase type 1. RCT=randomised controlled trial. *Anti-TNF monoclonal antibody conjugated to a
GRM. It selectively delivers GRM to the activated immune cells that express transmembrane TNF. Intended to increase overall efficacy while reducing systemic effects of
conventional glucocorticoids. †Small-molecule inhibitors of 11β-HSD-1. This enzyme converts inactive cortisone to active cortisol in tissues.

Table 2: Ongoing clinical trials in patients with polymyalgia rheumatica

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treated with IL-6 receptor blockers (see next section), due
to the direct inhibition of the acute phase reactant
synthesis.128,129 Except in this context, relapses with
completely normal acute phase reactants are infrequent41,42
and overdiagnosis of polymyalgia rheumatica flare needs
to be avoided by referral to expert centres since other
conditions can present with a polymyalgic syndrome
(table 1). Conversely, inflammatory indices can some­
times rise for other reasons in the absence of clinically
active disease and isolated fluctuations in acute phase
reactants should not be considered relapse in the absence
of clinical symptoms.
Glucocorticoid-induced adrenal insufficiency, with
symptoms of arthralgia, myalgia, malaise, abdominal pain,
and fatigue, can occur in 11% of people receiving long-term
treatment, particularly when prednisone dose is reduced to
less than 7·5 mg per day, and can further complicate
relapse assessment.130 The absence of more characteristic
symptoms and laboratory abnormalities of polymyalgia
rheumatica can prompt the suspicion of adrenal
insufficiency. Adrenal insufficiency can be substantiated by
a short 250 mg corticotropin stimulation test and might
require endocrinologist consultation, particularly in the
context of infection or acute stress. Most cases resolve over
time with slow tapering. Treatment, inflammation, or
inactivity-related muscle weakness, as well as osteoarthritis
and tendinopathies, common in this age group, can also
make assessment of response and relapse difficult (table 1).
The role of imaging for assessing relapse remains
unclear. Follow-up studies using different imaging
methods have indicated that reduction of inflammation-
related abnormalities only partly parallels clinical
improvement. In one study, 20 people with polymyalgia
rheumatica received three infusions of tocilizumab at
weeks 0, 4, and 8 and were followed up clinically, by
¹⁸FDG-PET-CT and MRI.116 Although all participants had
clinical remission or low disease activity at week 12, only
moderate reduction of inflammatory lesions at shoulders
and hips were observed by imaging. Other studies
revealed similar results.131–133 Whether residual imaging
abnormalities correspond to smouldering inflammation
or to remodelling, and whether these findings are relevant
for therapeutic decisions and long-term outcomes is
unclear. Imaging as a tool to monitor polymyalgia
rheumatica activity is still investigational.
There is no universally agreed definition of polymyalgia
rheumatica relapse for research studies.134 A threshold
level in the CRP–polymyalgia rheumatica activity score
has been used to define relapse.135 However, polymyalgia
rheumatica activity score also incorporates a physician
global assessment that introduces circularity to validation
studies. In general, the reference standard for assessing
relapse definitions relies on subjective clinical judge­
ment, which is not perfect and might be influenced
by contextual factors. The Outcome Measures in
Rheumatology (OMERACT) polymyalgia rheumatica
working group identified a core domain set including
1468
pain, stiffness, physician function, and laboratory
markers and corresponding instruments to measure
these domains for clinical trials.136,137
Other outcome measures
A comprehensive Glucocorticoid Toxicity Index has been
developed to support systematic assessment for
glucocorticoid toxicity in trials designed to reduce
glucocorticoid exposure.97 An OMERACT initiative that
included participants with polymyalgia rheumatica and
physicians led to the inclusion of fatigue,138–140 which is
not specifically assessed in the expert-developed Gluco­
corticoid Toxicity Index. Although these instru­ ments
were developed for investigational purposes their content
can guide physicians in the long-term management of
polymyalgia rheumatica.
Isolated polymyalgia rheumatica does not convey life-
threatening complications and does not lead to permanent
organ damage; however, the burden of recurrent disease
and glucocorticoid side-effects can deeply impair the
quality of life of some people with the condition.136,137 Both
physical and mental components of generic measures of
health-related quality of life, including the Medical
Outcomes Study Short Form 36 and Euroqol EQ-5D, are
affected by polymyalgia rheumatica.136,137 On average,
health-related quality of life improves with time but there
is substantial heterogeneity in polymyalgia rheumatica
trajectories over time.138–140 A polymyalgia rheumatica-
specific patient-reported outcomes measure, including
assessment of four domains (ie, symptoms, function,
psychological and emotional wellbeing, and glucocorticoid
side-effects), has been developed.141 Although these
assessments have been developed for research, they are
relevant to patients and need to be considered, together
with patient preferences and values, in shared decision
making for optimal care.
Future directions for practice and research
There are many unmet needs in the diagnosis and
management of people with polymyalgia rheumatica.
The role of imaging in its various modalities in the
diagnosis and assessment of disease activity needs to be
better defined and validated. Disease stratification
according to severity and risk of unfavourable outcomes
needs to be defined, along with the role of imaging and
serum or tissue biomarkers for this purpose. Current
treatment options are inadequate, particularly for people
with truly refractory or relapsing polymyalgia rheumatica
and those with or at high risk of glucocorticoid-related
adverse events. A better understanding of polymyalgia
rheumatica physiopathology could lead to a more
accurate selection of biomarkers and targeted therapies.
Clinical trials support the clinical benefit of several
targeted therapies, particularly tocilizumab and
sarilumab. Where specialist referral is indicated, fast-
track clinics might play a role in speeding diagnosis,
stratifying severity, and optimising treatment.
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Since polymyalgia rheumatica does not lead to permanent
organ damage and targets older individuals (aged ≥50 years)
with increased vulnerability, the trade-off between the
benefits and risks of new therapies, which might increase
risk of infection (eg, rituximab and JAK inhibitors),
malignancy, or vascular morbidity (eg, JAK inhibitors),
compared with low-dose gluco­ corticoid monotherapy
maintenance, needs to be carefully evaluated.
Contributors
MCC and GE-F designed the outline of this Seminar. All authors
contributed by writing two sections and thoroughly reviewed the
sections written by others. MCC and GE-F composed the final
manuscript, which was reviewed and approved by all contributors.
Declaration of interests
GE-F reports consulting fees from Janssen, GSK, and CSL Vifor, and
meeting travel support from Boehringer Ingelheim. CD reports grant
support from AbbVie, Novartis, and Celgene; consulting fees, speaker
fees, or both honoraria from AbbVie, Roche, Sanofi, Galapagos, Lilly,
Janssen, Novartis, and Sparrow; participation in advisory boards for
Roche, Sanofi, AbbVie, Janssen, Novartis, Eli Lilly, Galapagos, and
Sparrow; meeting travel support from AbbVie, Roche, Sanofi, Galapagos,
Eli Lilly, Janssen, and Novartis; and royalties from Oxford University
Press and SAGE journals. CD reports participation in the EULAR
congress committee. SLM received a research grant from CSL Vifor and
from the National Institute of Health Research; consulting fees from
AbbVie, AstraZeneca, Roche/Chugai, and Sanofi; lecturing fees from
Pfizer, UCB, and CSL Vifor; and meeting travel support from Roche/
Chugai and Pfizer. SLM is a patron of the charity Polymyalgia
Rheumatica and Giant Cell Arteritis UK. CS reports consulting fees from
AbbVie, Boehringer Ingelheim, Roche, Lilly, Galapagos, Pfizer, Novartis,
and Amgen, and royalties from UpToDate. ELM reports a research grant
from AbbVie; consulting fees, lecturing fees, or both from Boehringer
Ingelheim and Novartis; royalties from UpToDate; and speaker fees from
Practice Point Communication. ELM reports participation in advisory
boards for National Institutes of Health and Horizon Therapeutics.
MCC reports consulting fees from GSK, AbbVie, CSL Vifor, Janssen, and
AstraZeneca; royalties from UpToDate; and a research grant and meeting
travel support from Kiniksa Pharmaceuticals. MCC reports participation
in advisory boards for GSK, CSL Vifor, and AstraZeneca.
Acknowledgments
Figure 1 was designed by Catalyzing Science. MCC was funded by
Ministerio de Ciencia e Innovación (AEI//10.13039/501100011033
[PID2020-114909RB-I00]) and by the Vasculitis Foundation.
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