PERSPECTIVE

The role of imaging in polymyalgia rheumatica/giantcell arteritis

William S. Wilke

Published online: 2 July 2008# ISS 2008

Introduction

Polymyalgia rheumatica (PMR) has a venerable hypothet-ical pathophysiologic history. Some thought it was primar-ily vasculitis, and others thought it was arthritis.

The term was inaugurated in 1957 by the Britishphysician Barber who treated patients at a spa in Buxton[1]. Prior to that time, series of patients with diagnoses suchas senile rheumatic gout, periarticular fibrositis, and,importantly, anarthritic rheumatoid disease were publishedand probably represent the earliest clinical descriptions ofPMR [2–4]. Articular and periarticular signs and symptomswere well-recognized by these observers.

Yet, another literature set evolved in parallel whichemphasized the vasculitic nature of PMR. In 1968, Hamrinand colleagues presented six cases of “polymyalgiaarteritica” in which clinically unsuspected characteristichistopathology in the superficial temporal arteries wasdiscovered in three patients and, at autopsy, three furtherpatients showed histopathologic signs of giant cell arteritisin the aorta or its branches [5]. They also reviewed similarcases from even earlier literature. Healey and otherspresented a strong argument that PMR and giant cellarteritis (GCA) were part of the same disease spectrum in1971 [6]. Alestig and Barr in 1963 and later confirmed byFauchald et al. in 1972 both published strong evidence thatthis was so [7, 8]. They showed that superficial temporalbiopsies were positive for GCA in up to 40% patients whohad only symptoms of PMR.

The modern literature supports this interpretation. Clin-ical PMR occurs initially in at least 30% of new GCApatients and may occur for the first time later in the coursewith disease flare as corticosteroids are tapered [9]. Inaddition, PMR and GCA share human leukocyte antigen-DRB1–04 alleles in the second hypervariable region [10].In addition, both diseases respond more or less to the sametreatment. All of this information suggests shared identity.

So, what is the place for imaging in PMR? A recentGCA “management guideline” concluded that “…noimaging tests are established in the routine evaluation ofpatients with giant cell arteritis” [11]. A closer look is inorder. Let us artificially separate the two diseases and beginwith PMR. The most commonly used criteria are inter-changeable.

Criteria for classification of PMR—Bird et al. [12]:

1. Bilateral shoulder pain /stiffness2. Duration of onset of 2 weeks or less3. Initial Westergren sedimentation rate (WSR) >40 mm/h4. Duration of morning stiffness >1 h5. Age=/>65 years6. Depression/weight loss7. Bilateral upper arm tenderness

Definite PMR is defined as the presence of three or morecriteria or, if less than three criteria, clinical abnormality ofthe temporal artery and positive response to corticosteroidtreatment.

Criteria for classification PMR—Chuang et al. [13]:

1. Age >50 years2. Bilateral aching/tenderness for one month of:

(a) Neck or torso(b) Shoulders or upper arms(c) Hips or thighs

Skeletal Radiol (2008) 37:779–783DOI 10.1007/s00256-008-0541-5

W. S. Wilke (*)Department Rheum/ORI, Cleveland Clinic Foundation,9500 Euclid Avenue/A50,Cleveland, OH 44195, USAe-mail: wilkew@ccf.org

3. Initial Westergren sedimentation rate >40 mm/h4. Exclusion of other diagnoses

Definite PMR requires the presence of all criteria.In agreement with the previous discussion, when

rheumatologists entertain a diagnosis of PMR, we refer toa set of signs and symptoms considered to be associatedwith clinical or subclinical GCA. The classification criteriafor GCA are as follows:

Classification criteria for GCA—Hunder et al. [14]

1. Age at onset=/>50 years2. New headache3. Temporal artery abnormality4. Elevated erythrocyte sedimentation rate5. Abnormal artery biopsy

Definite GCA requires the presence of at least threecriteria.

Although PMR and GCA often share identity, somepatients with symptoms indistinguishable from PMR haveother underlying causes. In these cases, PMR is indeed asyndrome indicating heterogeneous diseases [15, 16].Under broad categories, these include infection, neoplasm,or other autoimmune disease. How might imaging help tosort this out? I can find no series in which imaging has beenused to differentiate PMR from neoplasm or infection. Ithas been used to distinguish PMR from primary inflamma-tory arthritis.

Elderly onset rheumatoid arthritis and PMRand differential diagnosis

Since the 1960s, many series have reported inflammatoryarthritis accompanying PMR, including some with simul-taneous GCA [9]. Joints most often mentioned were theshoulder, knee, wrist, metacarpal phalangeal, and sterno-clavicular. Healey emphasized the difficulty in differentiat-ing PMR from rheumatoid arthritis (RA) of the elderly [17].Chou and Schumacher confirmed the existence of mildhistologic synovitis in the knees and sternoclavicular joints[18]. But even in these studies, using less sophisticatedimaging techniques than are presently available, there weredifferences. Synovitis in PMR was rare and was thecommon hallmark of RA. Bony erosions, nearly universalin RA, were not seen in PMR. Since imaging techniqueswere much less precise than they are today, could thesemore precise techniques be used to advantage for differen-tial diagnoses?

J Desmomd O’Duffy and colleagues were the first toshow evidence of synovitis in the shoulders and other jointsin patients with PMR using technetium-99 pertechnetatescintigraphy [19]. Counts were elevated in the shoulders in

20/25 (80%) of PMR patients. He also included controls,among them, 16 patients with RA, of whom counts wereelevated in eight (50%; p=0.04). When they compareduptake in all joints in the two diseases, RA patients showedgreater symmetry and distal joint abnormalities predomi-nated. For instance, 64% of PMR patients demonstratedincreased counts in the hands compared to 88% of RApatients (p=0.09).

Hantzschel and colleagues reported a study designed toseparate RA from PMR using scintigraphy [20]. Theycompared 16 patients with PMR using the criteria of Bird to23 patients with RA, using American Rheumatism Associ-ation 1987 criteria. Scintigraphy employed technetium-99 m pertechnetate. Twenty-seven laboratory tests and avariety of clinical signs were also analyzed. “Only”bilateral upper arm pain or stiffness, or “both”, as a clinicaltest encountered more frequently in PMR and rheumatoidfactor, more frequent in RA, distinguished the two groups.Shoulder joint scintigraphy showed no differences in thecounts between the two diseases, and was not useful.

From these two studies, only the pattern of scintigraphicuptake differentiates the two diseases. The differences injoint uptake between diseases were of small magnitude andprobably not useful to classify individual patients.

Alternatively, magnetic resonance imaging (MRI) maybe more helpful. Salvarani and colleagues compared MRfindings in the shoulders in 13 PMR patients to nine RApatients [21]. Signs of periarticular inflammation and fluidin the subdeltoid bursa best differentiated the two diseases,occurring in 100% 0f PMR patients compared to 22% ofRA patients (p<0.001). The frequency of joint synovitis,55% in PMR and 77% in RA, did not significantly differbetween groups.

Fat suppression magnetic resonance imaging of theshoulders in another study confirmed the previous findings.Magnetic resonance appearance of the shoulders of 14patients with PMR was compared to those of 14 patientswith RA [22]. Nine of 14 patients (ten of 20 joints) withPMR but only two of 14 patients (two of 20 joints) with RAshowed prominent edema of extracapsular sites adjacent tothe joint capsule or in the soft tissues (p=0.02).

Another study analyzed the joints of the hands usingdynamic contrast-enhanced and conventional MR [23]. Tenpatients each with either PMR or RA were studied. Ahigher proportion of PMR patients showed extracapsularenhancement, ten of ten for PMR versus five of ten for RA(p=0.030).

Ultrasonography has also been used to study thesediseases. Fallsetti and colleagues studied multiple jointsand enthuses on the value in 50 patients each with PMR,RA, or seronegative spondyloarthropathy [24]. No differ-ences in synovitis or effusions were seen in the hips andshoulders. The best differentiation was seen in comparison

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of elbows, knees, and wrists. Elbow and knee effusions andenthesitis were encountered approximately 10–30% in RAand in 5–0%, respectively, in PMR (p<0.05, 0.01).Wristeffusions were shown in 20% of PMR patients and 90% ofRA patients (p<0.01). Differences in other joints andentheses were insignificant.

Vascular imaging for differential diagnosis

Because PMR is a syndrome, finding subclinical largevessel involvement might facilitate differential diagnosis bydemonstrating that the relatively nonspecific symptoms inan individual patient are due to vascular inflammationwhich is also seen in GCA.

Since separate papers by Sproul and Hawthorn (1937)and Gilmore (1941), clinicians and pathologists haverecognized that involvement of larger arteries with histo-pathology reminiscent of the superficial temporal arteries inGCA occurs in those same patients with GCA and PMR[25, 26]. Among the early reports, that of Osberg was mostcomplete [27]. Necropsy of the aortas and muscular arteriesof 15 patients with GCA and one with Takayasu arteritiswere reported. The aorta was involved in all reportedpatients. In addition, the carotid and brachial arteries wereinvolved in the majority. Histopathologic findings includednecrosis in the media, thickening or destruction of theelastic lamina, and multinucleated giant cells adjacent toareas of necrosis.

Because these earlier series described histopathologicchanges after death, so by definition, late and terminaldisease is appropriate to generalize findings to a livingpopulation of patients with these diseases. More contem-porary series among patients with these diseases prior todeath have somewhat supported the earlier autopsy data.For instance, the risk of death from aortic aneurysm hasbeen reported to be up to 17.3 times greater than in thegeneral population [28]. Aortic dissection may be eitherearly or late in the disease, and while acute phase reactantsare elevated in 92%, of 33 patients, symptoms of GCA orPMR were absent in 48% [29].

Is the frequency of detectable large vessel involvementusing newer imaging methods sufficiently high to providespecific and sensitive criteria for differential diagnosis?Gallium 67 uptake in the temporal region of nine consecutivepatients with GCAwas compared to temporal region uptakein nine consecutive PMR patients, thought to be “pure” PMRwithout any GCA symptoms and to six patients who hadundergone scanning for other diagnostic considerations [30].Uptake was demonstrated in all nine patients with eitherPMR or GCA and in none of the controls.

Seven vascular regions in 36 PMR patients were studiedusing 18-fluorodeoxyglucose positron emission tomogra-

phy (PET) without controls [31]. Uptake was demonstratedin 11 (31%) primarily in the subclavian arteries but also inbrachial arteries and the aorta.

In a similar study of 13 untreated PMR patients but withsix control patients having unrelated inflammatory diseases,PET scanning demonstrated accumulation in the aorta andits branches in 12/13 PMR patients and none of the controls[32]. Eight PMR patients underwent repeat scanning duringtreatment and showed diminished uptake which correlatedwith symptom remission and much improved laboratorymeasures of inflammation, which implies that the quantityof 18-fluorodeoxyglucose vascular accumulation of was infact a measure of disease activity.

Duplex ultrasound alone has been used to demonstratelarge vessel involvement to facilitate the early diagnosis ofGCA. The axillary, subclavian, and brachial arteries wereimaged in an inception cohort of 176 GCA patients at thetime of diagnoses [33]. Homogeneous vessel wall swellingwas demonstrated in at least one artery. When the patientwith large vessel vasculitis findings were compared to thosewithout, headache, jaw claudication, ischemic optic neuritiswere less common in patients with large vessel involve-ment. Duration to diagnosis was also longer in patients withlarge vessel vasculitis. The initial WSR and symptoms ofPMR were not different between groups.

A similar technique, color Doppler ultrasonography, hasbeen reported to demonstrate inflammation in the superfi-cial temporal artery to improve diagnostic precision [34,35]. A critical overview of that controversial literature isbeyond the scope of this discussion.

The studies using gallium uptake and PET scanningsuffer from relatively low numbers of patients entered orlack of controls, but if imaging protocols can be readilystandardized and repeated in larger studies with appropriatecontrols, both gallium uptake and PET scanning couldprovide relatively sensitive and very specific testing toseparate the nonspecific syndrome PMR from patients withPMR symptoms due to subclinical vascular inflammationconsistent with GCA.

To monitor disease

As presented earlier, PMR and GCA likely representspectrums of the same disease. In GCA, subclinical aortitiscan develop and become clinically significant aorticdissection. A review of important selected reports regardingthe use of vascular imaging as tools for monitoring diseasefor this clinical eventuality is indicated.

Angiographic study of 65 GCA patients using combinedangiography, computed tomography, and MRI revealedinvolvement in the upper extremities in 61 patients, thelower extremities in 13, and in both in nine patients [36].

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From a practical perspective, the simultaneous use ofmultiple imaging techniques as a standard protocol wouldbe prohibitively expensive and cannot be recommended.This report is valuable, however, in that it demonstrates thehigh frequency of clinically silent large vessel involvementin GCA.

The frequency of aortitis was demonstrated in anotherseries using combined MRI and ultrasound imaging of theaortic arch. In this cross-sectional evaluation of 54 GCApatients with a mean follow-up of 5.4 years, significantaortic structural damage resulting in aneurysm was demon-strated in 12 (22.2%) patients [37]. Five of these 12 patientswere subsequently deemed surgical candidates. Of interest,patients with aortitis had lower WSR, had fewer relapses,and required shorter duration of therapy to corticosteroidwithdrawal when compared to those without aortitis.

Directed MRI studies in six GCA patients with evidencefor active disease/aortitis based on extremity claudication,elevated Westergren sedimentation rate, and/or abnormalchest X-ray detected vessel wall thickening and edema inall six patients [38]. These imaging signs improved withtreatment in all patients. Directed MRI in this seriesconfirmed the diagnosis of aortitis associated with GCA.

Conclusions

Newer and more sophisticated imaging techniques can beapplied to patients with PMR. Shoulder joint MRI imagingand ultrasound of the hands hold some promise astechniques which can differentiate PMR from older onsetRA [21, 23, 24]. Gallium and PET scanning and ultraso-nography can detect underlying often clinically insignifi-cant large vessel vascular involvement to secure a diagnosis[30–33]. By analogy, imaging may be useful to differentiatePMR from infection or neoplasm.

Clinically significant aortitis which can result in aneurys-mal dissection and when suspected by symptoms or asymp-tomatic elevation of acute phase reactants can be detectedusing MRI [28, 29, 36–38]. Clearly, imaging studies canfacilitate diagnosis and improve monitoring of vasculardisease in subsets of patients with PMR/GCA. Whetherimaging studies should become routine or only applied inindividual clinical scenarios requires further study.

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