POLYMYALGIA & GIANT CELL ARTERITIS RHEUMATOLOGY MATTERS! POLYMYALGIA & GIANT CELL ARTERITIS

Polymyalgia Rheumatica and Temporal Arteritis

Polymyalgia and Temporal Arteritis. Clinical syndromes which represent different ends of a disease spectrum. Affects elderly patients--is rare below 50. Respond to steroids.

Classification of Symptoms. Systemic--malaise, anorexia, fever, night sweats, weight loss, depression. Myalgic--proximal, symmetrical muscle pain and stiffness in PMR.

Classification of arteritic symptoms Pain, swelling, erythema over affected artery. Partial occlusion resulting in claudication-like symptoms. Total occlusion resulting in ischaemia and necrosis (can occur anywhere in body).

Polymyalgia Rheumatica Stiffness in morning which may worsen again in the evening. May literally have to roll out of bed in morning. Muscle strength generally preserved.

Temporal Arteritis. Almost only seen in Caucasians. Pain commonly around temporal artery, jaw and post auricular artery. Less common presentations may lead to pain in tongue, throat and teeth. Loss of pulsation of artery is a debatable sign. Histology reveals giant cell arteritis in 80% of cases.

Ophthalmic Features. Sudden, painless deterioration of vision in one eye, usually on waking. Visual acuity varies from 6/6 to no light perception. Fundus examination reveals optic disc oedema with splinter retinal haemorrhages. Starts as unilateral condition but may progress to bilateral disease.

Other Manifestations of GCA. Giant cell artertitis can affect all arteries. One study revealed 8 out of 244 patients with new stroke had GCA or PMR. May lead to isolated cranial nerve palsies. GCA can affect coronary arteries which may lead to myocardial infarct. Great vessels can be affected, there is an association with aortic incompetence.

Diagnosis PMR in particular is a diagnosis of exclusion. History is critical. Systemic, local and visual symptoms should be sought. Examination should include full cardiovascular and neurological review as well as eliciting local arteritic signs. The examination in PMR tends to be normal.

Differential Diagnosis for PMR. Neoplastic disease. Cervical spondylosis. Rheumatoid arthritis. Connective tissue disease. Myeloma and leukaemia. Bone disease (osteomyelitis). Hypothyroidism. Miliary TB.

Differential Diagnosis of TA. Dental conditions. Trigeminal neuralgia. Otological conditions. Retinal vascular accident. Other causes of opthalmoplegia.

Investigations ESR/Plasma viscosity raised in 80% but very non-specific. ALP marginally raised in 30-50%. Other features include thrombocytosis, raised IgG and a normocytic, normochromic anaemia. Histology remains the gold standard.

Histology. Biopsy of artery only justified if arteritis suspected. A negative biopsy dose not exclude TA. Giant cell arteritis is characterized by skip lesions. An inch of artery should be removed, preferably from a tender area.

J.W. male d.o.b.3/10/34 Oct 91doing building work at home myalgia thighs & buttocks morning stiffness to mid afternoon difficulty walking lethargy

J.W. male d.o.b.3/10/34 Dec 91 progressively worse shoulder girdle myalgia unable to crouch/elevate arms night sweats no energy no headaches

J.W. male d.o.b.3/10/34 normal temporal arteries no muscle tenderness moderate restriction shoulders & hips ESR 88 prednisolone 15 mgs/day better in 48 hrs ESR 14 within 2 weeks

J.W. male d.o.b.3/10/34 Dec 92: well on prednisolone 5 mg/day Jan 93: altered bowel habit rectal bleeding rectal carcinoma resected Nov 93: right knee effusion (ESR 7) Aug 95: right shoulder synovitis prednisolone 1mg/day July 96: stopped steroids. Well. ESR 9.

Mrs. D.E. female d.o.b.7/7/27 Oct 96: pain stiffness right hand shoulder,both knees morning stiffness shoulder & pelvic girdles anorexia & weight loss 9kg

Mrs. D.E. female d.o.b.7/7/27 Feb 96: severe headaches,flashing lights pain in tongue & throat when eating tender scalp & nodules on temples anorexia & weight loss 15kg O/E nodules (R) temporal artery no temporal pulse palpable ESR90 , gamma GT 136 TA biopsy: active giant cell arteritis

Mrs. D.E. female d.o.b.7/7/27 prednisolone 40mg/day. resolutionof symptoms in days 1996/7: unable to keep disease suppressed with less than 15mg prednisolone/day methotrexate added steady reduction of steroid thereafter July 99: well. Stopped steroid. Continues methotrexate. ESR19.

Polymyalgia Rheumatica and Giant Cell Arteritis Steroid treatment How much ? How long ? Complications

Polymyalgia Rheumatica Initial dose: 15mg Prednisolone daily for 1 month Reducing dose: by 2.5mg every 2-4 weeks to a dose of 7.5mg - 10mg daily then by 1mg every 4-6 weeks Maintenance dose: 10mg by 6 months 5mg by 1 year Most patients require steroid treatment for at least 3-4 years

Giant Cell Arteritis Do not wait for the temporal artery biopsy - treat immediately. Initial dose: 40mg Prednisolone daily for 8 weeks 80mg Prednisolone if eye symptoms Reducing dose: by 10mg/day at weekly intervals to 40mg and then 5mg/day to a dose of 10mg daily from 10mg rduce at 1mg intervals as PMR

Common concerns with treatment Do not reduce steroids too quickly. Apart from acute relapsing eye disease do not increase steroid dose for about 1 week after an apparent flare. The flare may be short lived. There is no place for Deflazacort. Intra-muscular steriods are currently under investigation. Early bone loss and diabetes should be considered Beyond 1 year, steroid-sparing agents should be used if the steroid dose remains 7.5 - 10mg +.

Do phenotypes like age, sex, ESR, IL-6 help? Maximum benefit - VS - Minimum side-effects Can we stratify patients ? Rapid responders Remitting / Relapsing Slow responders Do phenotypes like age, sex, ESR, IL-6 help? No! Weyand et al. Mayo clinic. Arch. Int. Med. 3/1999

Steroid induced Osteoporosis Common Early onset (2.5% loss 3 months. 5% loss 1 year)* Mechanisms: decreased calcium absorption increased urinary calcium excretion decreased sex hormones reduced osteoblast formation decreased muscle mass effects on growth factors Prevention of bone loss with cyclical etidronate** * Lo Casio et al. Bone & Mineral Research.Aug’ 90 ** Adachi et al. New Eng. J. Med. 1997;337

Steroid induced Osteoporosis Accounts for 10% of osteoporosis in both sexes. Walsh et al BMJ Aug. 1996: Nottinghamshire study: GP population of 65,786. 303 cases (65% female) on ‘continuous’ steroids mean daily dose 8mg mean duration of 3 years 23% RA 22% PMR 19% CAL

Results: Only 14% of people taking any preventative treatment for osteoporosis in the last 4 years. Only 10% of women over the age 45 and on steroids were taking HRT. Assuming the study representative of general population then approx 250,000 people in the UK, on steroids, were not on prophylaxis. Hospital based practice? - Worse!!! Reid et al. Aberdeen study (BMJ 1998)

Mrs T 74yrs Jan 1993 - 3yr history of temporal headaches - Inconclusive TA biopsy (1992) - Treated successfully with steroids (3 days) Recurrence of temp.headaches, also aches in shoulder girdles, Rt. buttock & thigh O/E - Tender TA. ESR=70 On Prednisolone 30mg for 3 days

Temporal Artery Biopsy Results “Sections of temporal artery show focal duplication and loss of elastic lamina but with no associated inflammation. Features represent a healed stage of temporal arteritis.” NB: steroid therapy for 7 days

ESR vs Prednisolone

Osteoporosis Assessment Menopause - 42 yrs # R wrist - 50 yrs # L patella - 63 yrs Steroid therapy c/o spinal pain - Thoracic wedge # DXA scan - results

Osteoporosis Treatment 1993 Rocaltrol 250 nanograms b.d Sandocal 1g o.d Calcitonin 50units 3 times weekly for 4 months 1996 Lowering BMD - Alendronate 10 mg o.d 1998 Improved BMD

Serial lumbar spine bone density

Subsequent course of condition 1993-94 Symptoms responded & did not recur but ESR 40-90mm/h 1994 Pred.5mg ESR40 1995 Pred.4mg ESR51 1997 Pred.3/2mg ESR46 1998 Pred.2/1mg ESR46 1999 Pred.1mg ESR27

Giant Cell Arteritis and Polymyalgia Rheumatica - Diagnostic difficulties The Normal ESR

What is the ESR? Rate of agglutination of red cells determined by fibrinogen level fibrinogen is an Acute Phase Reactant main stimulus Interleukin-6 source of IL-6 in PMR/GCA? IL-6 level correlates with disease activity

Is PMR/GCA a viable diagnosis with a normal ESR? Retrospective analysis of cohorts of PMR cases: 1) Gonzalez et al : ESR<40 20% of 201 cases more frequent in: men; younger patients less fever no weight loss no anaemia or electrophoretic abnormalities

2) Helfgott & Kieval : ESR<30 20% of 117 cases men more frequent higher Hb much longer disease duration before treatment

Are these cases really PMR/GCA? Retrospective studies cases already included on clinical grounds in ACR GCA criteria ESR excluded from classification tree due to low specificity best predictor is temporal artery tenderness or decreased pulsation

Summary PMR/GCA can be present in the absence of an elevated ESR generally indicates less severe disease

Giant Cell Arteritis and Polymyalgia Rheumatica - Diagnostic difficulties The Young Patient

often associated with malignancy no trials very rare under 50 years often associated with malignancy poor steroid response no trials

The Normal Temporal Artery Giant Cell Arteritis and Polymyalgia Rheumatica - Diagnostic difficulties The Normal Temporal Artery

variable percentage of biopsies in GCA are positive ?poor selection previous steroid therapy ‘some’ PMR patients have positive biopsies ? positivity rate in clinically normal arteries

SUMMARY do not overtreat PMR ‘in case’ of GCA consider prevention of steroid-induced osteoporosis atypical cases of GCA/PMR occur rarely