A Diagnosis of Polymyalgia Rheumatica and Giant Cell Arteritis

Polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) frequently occur together. And, while both share elevated inflammatory markers, their diagnosis and treatment differ.

In this review, led by Frank Buttgereit, M.D., Deputy Head of Rheumatology and Clinical Immunology at Charite University Medicine hospital in Berlin, researchers summarize the current evidence for diagnosing and treating polymyalgia rheumatica (PMR) and giant cell arteritis (GCA). The review was published in the June 14 issue of JAMA.

Buttgereit and colleagues searched MEDLINE, EMBASE, and Cochrane databases for studies published through March 30, 2016. The final count included 50 studies:  20 randomized clinical trials for therapy with 1,016 participants and 30 imaging studies for the diagnosis and/or assessment of response to therapy with 2,080 participants.

While polymyalgia rheumatica typically presents with bilateral upper extremity pain, subdeltoid bursitis and muscle or joint stiffness, giant cell arteritis presents with a host of other symptoms, such as unilateral or bilateral headache, myalgias, fatigue, fever, weight loss and sometimes vision loss, these are essentially different manifestations of the same disease - or, overlapping conditions, the authors of the review wrote.  [[{"type":"media","view_mode":"media_crop","fid":"49535","attributes":{"alt":"©Lightspring/Shuttersstock.com","class":"media-image media-image-right","id":"media_crop_237787581239","media_crop_h":"0","media_crop_image_style":"-1","media_crop_instance":"6000","media_crop_rotate":"0","media_crop_scale_h":"0","media_crop_scale_w":"0","media_crop_w":"0","media_crop_x":"0","media_crop_y":"0","style":"font-size: 13.008px; line-height: 1.538em; float: right;","title":"©Lightspring/Shuttersstock.com","typeof":"foaf:Image"}}]]

Some 40-60 percent of patients with giant cell arteritis also have polymyalgia rheumatica, whereas 16-21 percent of patients with polymyalgia rheumatica have giant cell arteritis.

Polymyalgia rheumatica and giant cell arteritis share risk factors such as susceptibility to HLA-DRB101 and HLA-DRB104 genotypes. They also share some pathogenetic pathways of the innate and adaptive immune system.

Polymyalgia rheumatica diagnosis

Polymyalgia rheumatica typically presents with bilateral upper extremity pain. Constitutional symptoms such as fatigue, depression, night sweats, weight loss and low-grade fever are frequent.

Elevated erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) or both are present in more than 90 percent of PMR patients; however, these tests are nonspecific, the authors wrote. If further evaluation is required, tests to consider include ultrasound of the shoulder, hip and peripheral joints. And, MRI of the spine and sacroiliac joints and vascular imaging.

Giant cell arteritis diagnosis

Giant cell arteritis typically presents with unilateral or bilateral headache, myalgias, fatigue, fever, weight loss and sometimes acute vision loss.

Patients with GCA frequently have cranial and/or systemic manifestations. The review noted that cranial features include new headache (2/3 of patients), temporal artery abnormality (a prominent, beaded and/or tender artery with decreased pulse (30% of patients), and abnormal temporal artery biopsy (these features are included in the 1990 ACR Classification Criteria).

Systemic features include polymyalgic symptoms, weight loss, fatigue, and fever. Vision loss occurs in as many as 20 percent of patients with GCA.

“The rapid evaluation of patients may reduce risk of vision loss, particularly because ischemic complications usually occur before glucocorticoid treatment,” the authors of the review wrote.

GCA is also associated with rarer ischemic complications, such as stroke, cranial nerve palsy and scalp necrosis. Large-vessel aneurysms and/or stenosis are potential short and/or long-term complications.

Atypical ESR and CRP test results may necessitate further diagnostic evaluation that may include temporal artery biopsy or imaging (vascular ultrasound, MRI or F-FDG-PET). The authors wrote that temporal artery biopsy remains the standard for definitive diagnosis.

Effective therapies

At this time, glucocorticoids as the most effective therapy for patients presenting both PMR and GCA, but the optimal dose and tapering treatment regimens are unknown, the authors wrote. Methotrexate may be added to glucocorticoids in patients at risk for relapse and in those with glucocorticoid-related adverse effects or need for prolonged glucocorticoid therapy.

The authors indicated that consensus-based recommendations for initial therapy for PMR is prednisone of 12.5 to 25mg/day or equivalent, and 40 to 60mg/day for GCA, followed by individualized tapering regimens in both diseases.

Adjunctive methotrexate may reduce cumulative glucocorticoid dosage by 20-44 percent and relapses by 36-54 percent in both PMR and GCA. Use of tocilizumab as additional treatment with prednisone showed a 2- to 4-fold increase in remission rates of GCA in a randomized clinical trial (N = 30).

Biological Agents

In PMR, a multicenter, 52-week double-blind RCT (n = 51) of infliximab (3mg/kg every 8weeks) and a single-center, 2-week double blind RCT (n = 22) of etanercept (25 mg twice per week) failed to meet their primary end points. In GCA, infliximab and adalimumab were ineffective in a multicenter, 52-week double-blind RCT (n = 44) and a multicenter, 52-week double-blind RCT (n = 70).

The interleukin-6 receptor blocker tocilizumab (8 mg/kg every 4 weeks) was tested in a small phase 2, 52-week double-blind RCT (n = 30) in GCA. Higher remission rates, lower cumulative glucocorticoid doses, and a shorter duration of glucocorticoid therapy were observed in the tocilizumab vs the placebo group. “There appears to be no evidence supporting the role for TNF-α–blocking agents,” the authors wrote.

References:

Frank Buttgereit, MD; Christian Dejaco,MD, PhD; Eric L. Matteson, MD, MPH; Bhaskar Dasgupta, MD.

"Polymyalgia Rheumatica and Giant Cell Arteritis A Systematic Review." 

JAMA. 2016;315(22):2442-2458. doi:10.1001/jama.2016.5444