Polymyalgia Rheumatica (and temporal arteritis)

Polymyalgia rheumatica (PMR) is an inflammatory rheumatism characterised by aching and morning stiffness about the shoulder and often hips. It can be associated with giant cell arteritis (GCA), also known as Horton disease, a vasculitis classically accompanied with the headache harbinger of potentially vision-threatening involvement of the temporal artery (temporal arteritis).¹ PMR and GCA may represent different ends of a disease spectrum.

Although relatively common, Polymyalgia rheumatica (PMR) is almost exclusively a disease of adults over the age of 50, with a prevalence that increases progressively with advancing age and peaking between ages 70 and 80. There is a 2.5% lifetime risk of developing PMR for women (1.66% for men); second only to rheumatoid arthritis (RA) as a systemic rheumatic disease in adults. About 10% of patients with PMR develop GCA but, critically, PMR can precede, accompany, or even follow GCA.¹

A diagnostic imperative therefore arises in any patient, classically a women in or after her 50s (0.5% incidence in the sixth decade) of northern-European descent, who presents with girdle symptoms: 1) to consider PMR as the diagnosis; and 2) to consider whether the patient also has GCA.

The onset of PMR can be abrupt, sometimes startlingly so, seeming to occur almost overnight, such that a history of longstanding stiffness and aching might suggest an alternate diagnosis. Bilateral shoulder pain is the rule (70-95%) at presentation, with frequent involvement also of the neck (70%) and hip girdle (50%). Distal symptoms, usually of the upper limbs (mainly wrist), can accompany the classic proximal symptoms. Morning stiffness, and gelling with inactivity—the hallmark of rheumatoid synovitis—is notably also severe in PMR; so much so that the absence of morning stiffness, again, should suggest an alternate diagnosis to PMR. Nocturnal pain is also common with PMR.¹

Patients with PMR can experience non-specific systemic symptoms of malaise, fatigue, depression, anorexia, weight loss, and low-grade fever. The occurrence of fever in suspected PMR should prompt a search for underlying GCA or other pathology, especially infection; but the high-spiking fever associated with giant-cell arteritis (GCA) is rare in patients with PMR alone.¹

Symptomatology:

• constitutional symptoms:
  • fever
  • fatigue
  • anorexia
  • weight loss
• rheumatism:
  • pain and stiffness
  • neck and shoulder, pelvic girdle
• +/- headache:
  • temporal artery tenderness or diminished pulse
  • jaw claudication
  • ischaemic optic neuropathy, unilateral >> bilateral within 1-10 days
  • other evidence of ischemia, e.g, arm claudication (large-calibre arteritis) 

Diagnostic clues:

• ESR: > 30 mm/hour in 92-94% at presentation
• CRP > 5 mg/L: 99% patients at presentation — a normal CRP effectively excludes the diagnosis of PMR
• anaemia of chronic disease may be present
• anticyclic citrullinated peptide (anti-CCP) antibodies usually negative (cf. RA)

Differential Diagnosis of PMR and GCA:

Fibromyalgia: pain is more generalised

Multiple myeloma: monoclonal gammopathy

Myalgias from statin therapy: elevated CK

Osteoarthritis: articular rather than peri-articular pathology

Polymyositis: weakness as well as muscle pain, elevated CK

Rheumatoid arthritis: erosive synovitis, anti-CCP, RF

A clinical assessment for the presence of giant cell arteritis (GCA) is critical in evaluating the patient with suspected PMR. Counsel all such patients to remain alert for the emergence of symptoms, at any time during the course of their illness, that could suggest GCA: especially new-onset headache, visual impairment, or jaw “claudication.” Ophthalmological evaluation is essential to assess any such development of ischaemic optic atrophy from GCA. Most visual loss occurs early in the disease. Late visual loss during therapy is uncommon.

Rapid resolution of PMR symptoms with low-dose glucocorticoids (prednisone 15-25 mg/day) is the rule, so that lack of response to initial corticosteroid therapy should raise doubt about the diagnosis of PMR. Response to low-dose glucocorticoid treatment can, however, also be seen in patients with other inflammatory arthritis, including rheumatoid arthritis (RA) and psoriatic arthritis. In contrast to pure PMR, giant-cell arteritis necessitates immediate and high-dose corticosteroid therapy while the patient awaits confirmatory temporal artery biopsy testing.³

Temporal arteritis is a medical emergency: immediately commence Prednisone 40-60 mg PO daily (methylprednisolone 250 mg q 6 hr), to be tapered over months to years. Clinical suspicion is supported by an ESR > 50 mmHg. Pathological confirmation is made with temporal artery biopsy. After several weeks of treatment, approximately one-third of patients are able to begin gradually reducing their prednisolone, over many months, and can eventually stop treatment.²

BSR/BHPR prednisolone-tapering regimen for GCA and PMR:

GCA	PMR
Prednisolone 40–60mg (not <0.75 mg/kg) continued for 4 weeks (until resolution of symptoms and laboratory abnormalities)	Prednisolone 15 mg for 3 weeks
Reduction by 10 mg every 2 weeks to 20 mg	12.5 mg for 3 weeks
Reduction by 2.5 mg every 2–4 weeks to 10 mg	10 mg for 4–6 weeks
Reduction by 1 mg every 1–2 months provided there is no relapse	Reduction by 1 mg every 4–8 weeks or alternate day reductions (eg. 10/7.5 mg alternate days)

Morbidity related to corticosteroid treatment of GCA and PMR is not insignificant, and includes osteoporosis, corticosteroid myopathy, bruising, emotional symptoms (e.g., insomnia, restlessness, hypomania, depression), hypertension, diabetes, elevated cholesterol, and fluid retention. Bisphosphonates, vitamin D, and calcium are effective for preventing bone loss in patients treated with corticosteroids.² There is a lack of definitive evidence for steroid-sparing drugs in polymyalgia rheumatica. Methotrexate is typically used for relapsing disease. Leflunomide and tocilizumab are being investigated.³

Immunopathology: Patients with PMR and GCA share specific human leukocyte antigens (HLA), such as DR4, and sequence polymorphisms (variability) within the DRB1 gene, not common to patients with Rheumatoid arthritis. Other immune “markers” of PMR and GCA include increased T helper 17 (Th17) cells and raised cytokine interleukin (IL) 6 levels, while regulatory T (Treg) cells are decreased.¹  While many patients may show evidence of subclinical arterial inflammation (activated dendritic cells, IL-1, IL-6) in temporal artery biopsies, interferon gamma-producing T cells are prominent in biopsy specimens of those with clinical GCA.¹ Various imaging studies (USS, CT, MRI, PET scanning) show that, rather than a true muscular process as the name polymyalgia suggests, it is in fact the proximal peri-articular structures, such as bursae and tendons, that are mainly affected in PMR. Often, clinical severity fluctuates in a seasonal manner suggestive of some cyclical trigger for immune flare in PMR and GCA. Additional MRI studies have suggested a potential role for capsular inflammation and an enthesitis (inflammation of the insertions of tendons, ligaments, and capsules) in the pathogenesis of PMR.¹

References

1. Salvarani, Carlo and Muratore, Francesco. “Clinical manifestations and diagnosis of polymyalgia rheumatica.” Version 19.0. UpToDate. Jan 13, 2021. Available at https://www.uptodate.com/contents/clinical-manifestations-and-diagnosis-of-polymyalgia-rheumatica.
2. Llew, David F., Owen, Claire E. and Buchanan, Russell R. “Prescribing for polymyalgia rheumatica.” Aust Prescr 2018;41:14-9. https://doi.org/10.18773/ austprescr.2018.001.
3. Ameer, Faisal and McNeil, Julian. “Polymyalgia rheumatica: clinical update.” Aus Fam Phys 43(6), Jun 2014.
4. Unwin, Brian. “Polymyalgia Rheumatica and Giant Cell Arteritis.” Am Fam Physician. 2006 Nov 1;74(9):1547-1554.