Polymyalgia Rheumatica/Giant Cell Arteritis

Polymyalgia Rheumatica/Giant Cell Arteritis Ronald J Rapoport, MD

Disclosures Grant/Research Support: AstraZeneca, Abbott Laboratories Speakers Bureau: Abbott laboratories, Amgen Inc., Forest Laboratories, Pfizer Inc., Lilly, UCB Inc.

Learning Objectives Describe the clinical features of Polymyalgia Rheumatica (PMR) Review treatment options for PMR Describe the clinical features of Giant Cell Arteritis (GCA) Review treatment options for GCA

Polymyalgia Rheumatica (PMR) Patients present with pain and stiffness of neck, shoulder girdle, and pelvic girdle of at least 4 weeks duration1 Frequent signs of systemic inflammation such as malaise, weight loss, low grade fever, and sweats Most patients have abnormal labs such as elevated CRP and ESR and anemia…but as many as 20% may have a normal ESR Elevated markers of inflammation may help differentiate PMR from other illnesses with similar presentations 1. Hudner CG. Giant Cell Arteritis and Polymyalgia Rheumatica. Med Clin North 1997;811:195-219

PMR No pathognomonic test to confirm diagnosis The systemic inflammation of PMR is so (usually) exquisitely responsive to corticosteroids-that prompt improvement has been suggested as a diagnostic criterion The pathophysiology of PMR is related closely to that of GCA and may be considered a form of GCA that lacks fully developed vasculitis2 2. Primer on the Rheumatic Diseases., 13th edition.

PMR In both PMR and GCA women are affected more often than men Diagnosis is considered unlikely in patients under 50 years old Scandinavians and those of Northern European descent considered at higher risk. Annual incidence rates approx. 20 to 53 / 100,000 persons over 50 yrs old. Lower risk groups (ie, Italian) annual incidence rate of 10 / 100,000 Primer of the Rheumatic Diseases 13th addition

PMR – Clinical Features Onset of aching of neck, shoulders, low back, hips, thighs mayand often does, occur abruptly The presentation is usually symmetrical and most often initially affects the shoulder girdle The pain usually peaks in the morning, but may also occur at night There may be difficulty doing such things as dressing and even getting out of bed

PMR – Clinical Features…

Fever and chills should cause one to consider GCA It may be difficult to differentiate PMR from a seronegative inflammatory arthritis, especially early in the disease course Proximal aches and hand edema may be found-especially in male patients, causing even more of a perplexing picture. These patients are usually extremely responsive to oral corticosteroids

PMR – Clinical Findings….

Periarticular structures such as the subdeltoid and subacromial bursae may be involved. There may also be biceps tendonitis and glenohumeral synovitis adding to the difficulty in securing an exact diagnosis3 Ultrasonography has demonstrated fluid in the bursae and also thickening and edema PET scans may also show increased uptake 3. Salvarini C, Cantini F, Oliveira I, et al. Proximal bursitis in active polymyalgia rheumatica. Ann Int Med 1997;1271:27-31.

PMR – Differential Diagnosis

Seronegative Polyarthritis Shoulder disorders Myopathies Parkinsonism Hypothyroidism Malignancies / Infections ? Fibromyalgia

PMR - Treatment PMR is dramatically responsive to corticosteroids

 Majority of pts respond to 20 mgs / day or less Some may need to start at 40 mg /day… Tapering an art not a science My approach: I taper to half the given dose after a meaningful response and then cautiously by 1-2.5 mg every two weeks or so.

Very slow tapering may be needed No good data on steroid sparing drugs—but could consider methotrexate

PMR PMR may remit-but also may recur-or at least symptoms that mimic the initial clinical presentation Some may need to take low dose corticosteroids for a more prolonged length of time Good prognosis – but be aware of GCA which may occur in approx 15% of patients with PMR…

Giant Cell Arteritis (GCA) GCA is a systemic inflammatory vascular disease which most frequently affects the extracranial branches of the carotid artery GCA is one of the most common vasculitides affecting those of European and North American descent (approx 1/500 in those 50 yrs and over)4 GCA may also affect the aorta and its primary branches in a similar fashion to Takayasu arteritis5 4. Lawrence RC, Helmick CG, Arnett FC, et al. Estimates of the prevalence of arthritis and selected musculoskeletal disorders in the United States. Arth Rheum 1998; 31: 778-99.

5. Mzksimowiscz-McKinnon K, Clark T, Hoffman GS. Takayasu and giant cell arteritis: a spectrum within the same disease. Medicine 2009;88: 221-6.

GCA / Clinical features

Consider strongest in patients over 50 yrs old Symptoms include throbbing, sharp, or even dull headaches (HA) HA may or may not be associated with scalp tenderness Visual loss may be sudden, painless, and irreversible… Half of patients may have jaw claudication-which could be considered almost disease specific

GCA / Clinical features…

Jaw claudication due to compromised blood flow to masseter @ / or temporal muscles and may occur shortly after chewing begins-or even after prolonged talking Various neurologic and large vessel findings… GCA may present as Fever of Unknown origin. Fever may be indolent and associated with malaise, fatigue, and weight loss-or may be spiking and associated with chills

GCA / Visual loss Considered a true ophthalmologic emergency Symptoms may include blurred vision, diplopia, scotoma, amaurosis fugax, and abrupt loss of vision Prior to steroids visual loss was reported as high as 58%-but since their use 5-15%6,7 Most common etiology of visual loss is anterior optic ischemia. Can be mimicked by occipital stroke and central retinal arterial occlusion 6. Salvarani C, Cimino L, Macchioni P, et al. Risk factors for visual loss in an Italian population-based cohort of patients with giant cell arteritis. Arth Care and Research.2005;53: 293-7.

7. Gonzalez-Gay M, Blanco R, Rodriguez-Valverde V, et al. Permanent visual loss and cerebrovascular accidents in giant cell arteritis: predictors and response to treatment. Arth Rheum 1998;41: 1497-504.

GCA / Visual loss If any evidence of visual disturbance or loss-promptly begin treatment. These symptoms can be reversed and further loss avoided. Approx 1/3 of pts will have visual loss greatly improved if steroid begun within 24 hrs of symptom onset Visual while on corticosteroid is very uncommon-approx 10% Initial treatment is pulse corticosteroids (one gram of methylprednisolone or equivalent) for 3 to 5 days followed by 1mg/kg of prednisone in divided doses

GCA / Aortic aneurysm Aortic aneurysm and dissection may occur in approx 20 % of patients Usually affects the thoracic aorta Patients may describe a tearing sensation of the upper back-but , often, there are no symptoms Diagnosis based on high clinical suspicion-as this may be a surgical emergency

GCA / Cerebrovascular complications Transient ischemic attacks (TIA) and cerebrovascular accidents (CVA) may occur in up to 10% of patients May be initial sign of the disease Carotid and vertebral arteries most commonly affected Increased risk factors include smoking, hypertension and visual loss8 Prompt treatment as in visual loss.

8. Gonzalez-Gay M,Garcia-Porrua C, Pineiro A, et al. Aortic aneurysm and dissection in patients with biopsy-proven giant cell arteritis from NW Spain. A population based study. Medicine 2004;83:335-41.

GCA / Diagnostic procedure… Temporal artery biopsy is the procedure of choice even if the findings of scalp tenderness, arterial thickening or absent artery pulsation are absent Findings most strongly associated with a positive biopsy include jaw claudication, diplopia, and abnormalities of the temporal artery on PE Visual loss, elevated ESR, HA, and constitutional symptoms not very helpful in predicting a positive biopsy result

GCA / Biopsy of artery… Commitment of long term corticosteroids demands that a histologic diagnosis is made True negative results may be present in 50% – 70% of patients False negatives may occur in 10%. This may be reduced by ensuring a biopsy of sufficient length and consider the contralateral side if the first negative Corticosteroids given for 2 weeks or even more usually do not interfere with the interpretation of results…so BIOPSY! Do not hold steroids while procedure pending

In summary for the GCA / PMR Syndrome‌

Isolated PMR

Pain in shoulder and pelvic girdle muscles Stiffness

Cranial Arteritis Headaches Scalp tenderness Ischemic optic neuropathy Jaw claudication CNS ischemia PMR

Fever / wasting Syndrome Fever and chills Anorexia / weight loss Night sweats Weakness Depression

Large- vessel GCA / aortitis Arm claudication ( aortic arch syndrome) Pulselessness Raynaud’s phenomenon Aortic aneurysm Aortic insufficiency PMR