PMR & GCA Janet Pope Professor of Medicine Division of Rheumatology University of Western Ontario Polymyalgia Rheumatica (PMR) Giant-Cell Arteritis (GCA) which is also called: Temporal Arteritis (TA)

Objectives 1.Define polymyalgia rheumatica (PMR) & giant cell arteritis or temporal arteritis (GCA or TA). 2.Describe the underlying pathophysiology of PMR and GCS. 3.Discuss risk factors, clinical features and treatment. 4.Discuss the prognosis of PMR & GCA

Polymyalgia Rheumatica Poly = many Myalgia = sore muscles Rheumatica = something to do with rheumatism

Case 70 year old woman, previously healthy She has an active lifestyle and is taking only a multivitamin January – she began to notice pain and stiffness in her shoulders She was told it was just “old age” by her family doctor and a friend told her it was probably “rheumatism” caused by the cold weather By February the pain and stiffness had become worse

Case The pain and stiffness was around her hips and low back and into her shoulders and neck She complained of fatigue which was new She was very stiff in the morning taking hours if not all day to get going She had lost her appetite and lost 4Kg What else do you want to know or ask?

Ask PMR patient about Temporal arteritis symptoms –HA, scalp tenderness, visual problems, jaw claudication, tongue pain, weight loss, fever Fracture history Diabetes Other medical problems

Case She was worried that she had cancer or something dreadful In March she went back to see you

Case 1 – P/E Afebrile, HR 88, BP 160/70, in NAD General exam – normal MSK exam normal ROM of joints, –no swelling, pain on ROM of hips and shoulders What investigations would you do?

Case CBC, ESR (CRP maybe) TSH Glucose Creatinine, liver enzymes, (maybe: lytes, CK) Maybe RF, ANA

Labs WBC 6.4 Hbg 103 Plt 489 ESR 73 CRP 65 RF and ANA were both negative Normal serum protein electrophoresis

What is the most likely diagnosis?

PMR Older woman (> 50, often far older) –Increases with age –It does not occur in the young Pain & stiffness in the hips and shoulders Profound morning stiffness Insidious onset (half are sudden onset) Associated Fatigue Weight Loss in less than half Inflammatory Markers (ESR, CRP, could also have anemia, thrombocytosis)

Polymyalgia Rheumatica

There is NOTHING wrong with the muscles Proximal achiness is from the joints We see inflammation of joints and peri- articular structures such as bursae PMR is a history of shoulder and hip girdle symmetrical stiffness, no findings usually on exam and a high ESR

How would you treat her? Write the prescription

Polymyalgia Rheumatica It is Exquisitively Sensitive to Corticosteroids like prednisone

Case 15 or 20 mg of prednisone per day Report back in a couple of days There should be nearly 100% improvement in 72 hours or less In 12 hours she felt almost completely normal and couldn’t believe it How long do we usually need to treat it?

Duration of Treatment for PMR Usual treatment (median) is 2 years Decrease prednisone to lowest dose that controls the symptoms Do we need to follow the ESR? What other treatment may you want to add?

PMR: Initial Treatment Prednisone mg per day The patient must be virtually back to normal of you don’t have the correct diagnosis Slowly wean down the steroids (example after a few weeks) and keep decreasing as symptoms are controlled Often after 10 mg, patients need to reduce more slowly (ex 1mg every month or two)

PMR: Steroid Weaning Prednisone 15 mg x 1 month Prednisone 12.5 mg x 1 month Prednisone 10 mg x 1 month Below 10 mg I reduce by 1 mg per month TOTAL: 16 – 18 months

Prevention of corticosteroid induced OP Steroids can “thin” the bones and anyone you expect to take >7.5 mg of prednisone for >3 months should be protected Calcium: 1500 mg calcium per day Vitamin D: 1000 to 3000 IU per day Bisphosphonate Likely order a baseline BMD if one has not been done over the last couple of years

Prognosis of PMR Average duration of corticosteroid use is about 2 years A sub-group of patients will require low- dose prednisone for much longer Occasionally Rheumatoid arthritis can present very much like PMR If we can’t reduce prednisone or if patient has DM or severe OP, then Mtx can be used as a steroid sparing drug

How often is PMR of sudden onset? What proportion of PMR develops GCA? What would you warn her about?

How often is PMR of sudden onset? –50% What proportion of PMR develops GCA? –10% What would you warn her about? –Visual changes – decreased colour vision, missing part of visual field, TIA –Get seen ASAP if this occurs –Side effects of prednisone

Case 2 77 year old woman HTN on HCT Borderline hyperlipidemia, treated by diet Hysterectomy at age 45 for metromenorrhagia

Case 2 She noticed the onset of right sided headaches, new and constant like a vice grip over her entire head These were associated with pain over the temple and it actually hurt to brush her hair

Case 2 She also was quite fatigued and had noticed low grade fevers No visual symptoms (i.e. loss of vision) or no symptoms of stroke (cerebrovascular accident) No PMR symptoms

Case 2 What is the most likely diagnosis? How do you treat immediately? What investigations would you do?

Case 2 Prednisone 50 to 60 mg per day Started on low dose ASA Sent immediately to the lab To return to the office the next day for preliminary results What would you order?

Case 2: labs Complete Blood Count (CBC) Erythrocyte Sedimentation Rate (ESR) C-Reactive Protein (CRP) Glucose, creatinine, AST, ALT

Case 2: labs Hbg 99 WBC normal Platelets normal ESR 130 mm/hr CRP 120

The Next Day The patient is feeling a bit better She is referred urgently to a rheumatologist (you phone and ask for apt ASAP) or general medicine What else should be done?

Temporal artery biopsy

Treatment High dose steroids until ESR normalizes Ischemic pain may take a long time to improve There is a risk of visual loss or stroke so taper is usually according to the inflammatory markers ASA especially is visual changes Prevention of ulcer (PPI) with ASA Rx or prevention of OP with bisphoshonate Steroid sparing drugs –There are data with Mtx to reduce overall amount of prednisone needed Treatment is often for 1.5 to 3 years but in some it may last forever 50% of GCA have PMR, but10% of PMR have GCA

Temporal (Giant-Cell) Arteritis Chronic granulomatous vasculitis affecting large arteries in older people Most are >60 years of age (average 72) Inflammation of the walls of large arteries –Cranial arteritis (most common): Temporal, occipital, ophthalmic –Subclavian, iliac/femoral –Aorta

Temporal (Giant-Cell) Arteritis Physical Examination –Very tender over temples (common) –Swollen, rope like temporal artery (rare) –Optic disc swelling due to ischemia

Temporal (Giant-Cell) Arteritis

Vision Loss

Transient repeated episodes of diminished vision are usually reversible. Sudden loss of vision is an ominous sign and is almost always permanent. If loss of vision in one eye, patient has a high risk of losing vision in other eye EMERGENCY: give iv 100mg solumedrol and make sure pt is taking ASA

Temporal (Giant-Cell) Arteritis Investigations –Complete Blood Count (CBC) Normochromic, normocytic anemia Reactive thrombocytosis WBC is usually normal –Erythrocyte Sedimentation Rate (ESR) Significantly elevated –C-Reactive Protein (CRP) Significantly elevated

Temporal Artery Biopsy

Inflammation Multi-Nucleated Giant Cell

GCA pathology There is a ring of granulomanous inflammation centered around the elastic lamellae within and bounding the media. Disruption of internal elastic lamina multinucleated giant cells intimal thickening and fibrosis as well as the central acute thrombus. nonspecific inflammatory infiltrate in the adventitia Fibrinoid necrosis

Disruption of internal elastic lamina

GCA biopsy If you treat prior to biopsy, what would be the chance of having a positive biopsy in one week, How about in one month? What does the classic biopsy show?

GCA biopsy If you treat prior to biopsy, what would be the chance of having a positive biopsy in one week, highly likely How about in one month? Still can be positive but partially healed, try not to wait more than 2 weeks but do not with hold treatment if suspicion is high (40% + when Rx with pred for >1 month What does the classic biopsy show? Disruption of internal elastic lamina, inflammation, maybe giant cells

GCA: Initial Treatment Prednisone mg per day (1mg/kg/d) I start at mg per day and hold on that dose until –The patient is feeling well –The inflammatory markers have normalized I then begin to slowly wean down the steroids (usually after a month or two)

GCA: Steroid Weaning Prednisone 50 mg x 1-2 month Then reduce by 5 mg every 2 weeks 20 mg (3 months) Then reduce by 2.5 mg every 4 weeks until at 10 mg (4 months) Then reduce by 1 mg every month (10 months) TOTAL: 18+ months

Prognosis of GCA Average duration of corticosteroids is 2.4 years A sub-group of patients who will have smoldering disease activity for much longer (7-10 years) Thoracic aneurysms can appear up to 15 years after initial diagnosis

Prognosis of GCA Most significant complications include: –Visual loss –Cerebrovascular accident (stroke) Mortality is due to vascular complications relating to inflammation What should you ask if you suspect GCA?

Case 2 - GCA PMR, other neurologic symptoms, duration of visual change, location of HA, jaw claudication, weight loss, fever, scalp tenderness, illness prior Other health issues: CAD, HTN, smoking, etc

Mortality in GCA Is mortality increased? What proportion of GCA has PMR? Is there a role for a steroid sparing drug in the treatment? What would you follow? How long is the median treatment of PMR and or GCA?

Is mortality increased? yes What proportion of GCA has PMR? 50% Is there a role for a steroid sparing drug in the treatment? maybe What would you follow? ESR How long is the median treatment of PMR and or GCA? 2+ years with a wide range

Seasonal Variation of GCA Chart review of GCA (bx proven and or met ACR criteria) between , N=206 Peaks in May – June in Jerusalem 3 peaks over 20 yrs but no increase in incidence 1.4 women to 1 man 11.3 per 100,000 incidence over 25 years Seasonal changes and ocassional peaks suggest an infectious or other environmental agent but none identified Breuer #1927

GCA Jaw claudication Scalp tenderness Anemia Fever Weight loss Visual change Swollen temporal arteries Pulseless temporal arteries Tender temporal arteries A positive biopsy

GCA Jaw claudication - uncommon Scalp tenderness - common Anemia - common Fever – 25% Weight loss – 25% Visual change – less than 10% Swollen temporal arteries – totally rare Pulseless temporal arteries - uncommon Tender temporal arteries - common A positive biopsy – depends on bx size and time after treatment – 75%

Conclusions PMR is common and patients should be virtually 100% better at most 72 hrs after starting prednisone (ex 15mg a day) Usual treatment is for a couple of years Use the lowest dose possible to control symptoms Temporal arteritis is an emergency Usually referral to a specialist after starting prednisone 50mg a day and ASA if diagnosis is strongly suspected