A 71-year-old woman presented with aching pain and stiffness in her arms, hands, knees and feet for several months. She responded well initially to steroid treatment but had difficulty tapering off the dose. Examination found symmetrical joint swelling. Tests showed elevated inflammatory markers. She was diagnosed with possible polymyalgia rheumatica or late-onset rheumatoid arthritis. Treatment with methotrexate and gradual steroid tapering was recommended.

1. Case presentation Prepared by Dr R Musa

2. GP referral 71 yrs old Lady presented few of months ago with : History suggestive of PMR Initially good response to 20mg of steroid Difficult to ↓ steroid, (recurrent symptoms), persist ↑ ESR 50, CRP 91 Required ↑ dose to 30mg Developed arthralgia with puffy hands

3. History C/O; Aching pain & stiffness in both arms, hands, knees & feet Morning stiffness > 3 hours Soft tissue swelling of both hands, swollen knees and ankles No skin rash, no excess hair loss & (no psoriasis or F/H of psoriasis No dry eyes / dry mouth No Wt loss, normal bowel habits & No urinary symptoms

4. Social history Never smoked. Retired, married. Medication Prednisolone 25mg daily Alendronic acid 70mg once a week Atenolol 100mg Doxazosin 8mg Bendrofluazide 2.5mg Paracetamol 1gm PRN Omeprazole 20mg

5. On examination No skin rash or nails changes. Symmetrical synovitis involving the 2 nd , 3 rd , & 4 th MCP joints of hands, wrists, knees & ankles No lymphadenopathy Chest: clear Heart: NAD

6. D/D PMR resistant to steroid therapy RA Sero-positive RA Sero-negative RA (LO sero (-) RA) Neoplasm Infection

7. Investigation RF 458 FBC (N) ESR 39 CRP 50 U&E (N), LFT (N) X-ray hands, Feet & CXR

8. erosion

11. Treatment LO-RA: MTX (10mg O/W & increase dose if no SE) If erosion increase MTX dose & added HCQ PMR: 15 mg prednisone dramatic response MTX (as steroid sparing) 87.5% of MTX-treated patients and 53.3% of patients treated with prednisone alone were no longer on steroids at 76 weeks. Significantly fewer patients on MTX had at least one flare up by the end of follow-up. Infliximab in the treatment of polymyalgia rheumatica: a double-blind, randomized, placebo-controlled study. Salvarani C, Macchioni PL, Manzini C, et al. Ann Intern Med (2007) no differences were observed among groups: the proportion of patients who were free of relapses/recurrences at 22 and 52 weeks was similar reducing dose of steroid should be based on sign & symptoms rather than CRP & ESR value, which dose not predicate relapse Therapy usually last two years, relapse usually in the 1st or 2nd month

12. PMR (diagnostic criteria) > 50–60 yrs Aching and stiffness in the shoulder and/or pelvic girdles > one month. ESR > 40 Rapidly responds to Prednisolone 15mg

13. Pathogenesis of PMR ↑ Production of IL-6 chronic stress lead to ↓ the hypothalamic–pituitary–adrenal (HPA) axis ↓ Production of adrenal hormones, like cortisol. Functional (21 –hydroxylase) impairment in PMR due to; Genetic defects or Age-related increase serum TNF & IL-6 levels TNF- was shown to inhibit the 21 -hydroxylase. Steroid acting as a replacement for the reduced endogenous cortisol production, seems to be more efficient in PMR. During steroid treatment ↓ ESR was more evident in PMR patients than in LO-RA patients.

14. Classic RA Symmetrical peripheral joints involvement. RF seropositivity Development of joint erosions Extra-articular manifestations Positive anti-citrullinated peptide (CCP) antibodies

15. Sero (-) LO-RA Mild symmetric synovitis in several patients with sero (-) LO-RA Non-erosive course Rapid and complete response to steroid. 35% negative for both RF & anti-CCP Notes; Symptoms and signs of both PMR and LO-RA might alternate during the follow-up of the patients 20% of PMR patients developed overt RA during the follow-up period

16. Polymyalgia rheumatica vs late-onset rheumatoid arthritis M. Cutolo1, M. A. Cimmino1 and A. Sulli1 ( Rheumatology 2009 48(2):93-95) In leeds teaching hospital - 10 years follow up of 142 Pt (LO-RA) 147 (PMR) 42 (PMR + TA) PMR & LA sero (-) RA are different disease High ESR + synovitis of wrist + one MCP/PIP at disease onset were; predictive of whether a non-erosive sero (-) patient would ultimately be diagnosed as having sero (–)LO-RA or PMR

17. Polymyalgia rheumatica vs late-onset rheumatoid arthritis M. Cutolo1, M. A. Cimmino1 and A. Sulli1 ( Rheumatology 2009 48(2):93-95) Slow response Dramatic response Response to 15 mg steroid HLA-DRB1 allele HLA-DRB1 allele HLA allele Mildly elevated higher ESR, CRP & IL6. ESR & CRP Main sign Less frequent More myalgia Arthritis of PIP, MCP and wrist joints Older Relatively younger Age > 80% 23% Synovitis Sero–ve LO-RA PMR