PMR & GCA

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

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

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

4. 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

5. 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?

6. 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

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

8. 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?

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

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

11. What is the most likely diagnosis?

12. 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)

13. Polymyalgia Rheumatica

14. 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

15. How would you treat her? • Write the prescription

16. Polymyalgia Rheumatica • It is Exquisitively Sensitive to Corticosteroids like prednisone

17. 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?

18. 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?

19. PMR: Initial Treatment • Prednisone 15-20 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)

20. 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

21. 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

22. 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

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

24. 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

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

26. 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

27. 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

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

29. 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?

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

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

32. 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?

33. Temporal artery biopsy

34. 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

36. 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

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

38. Temporal (Giant-Cell) Arteritis

39. Vision Loss

40. 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

41. 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

42. Temporal Artery Biopsy

43. Temporal Artery Biopsy Inflammation Multi-Nucleated Giant Cell

44. 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

45. Disruption of internal elastic lamina

46. 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?

47. 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

48. GCA: Initial Treatment • Prednisone 50-60 mg per day (1mg/kg/d) • I start at 50-60 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)

49. GCA: Steroid Weaning • Prednisone 50 mg x 1-2 month • Then reduce by 5 mg every 2 weeks until @ 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

50. 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