Transcript PMR/GCA
Giant Cell Arteritis&Polymyalgia Rheumatica Olabambo Ogunbambi Consultant Rheumatologist Hull Royal Infirmary Epidemiology Pathogenesis Clinical Features Investigations Imaging Mimics Treatment Giant cell arteritis Primary systemic vasculitis medium/large vessels involves aorta & main branches First described by Hutchinson 1890 Histological features described by Horton et al 1932 Epidemiology Most common vasculitis Europe/N america Incidence increases with age Women affected 2-3 times more commonly Incidence increases with latitude 17/million in North American populations of Scandinavian descent (over age 50) <12/million in South European populations Rare in blacks and Asians Pathogenesis Still much uncertainty Factors implicated Age Genetic factors Infection(?) seasonal variation incidence Pathogenesis Genetic factors HLA Association with HLA DRB1*04 TNF microsatellite polymorphisms Functional variant VEGF gene Polymorphisms in genes for IL-13, NOS2, TLR-4 Pathogenesis Both innate and adaptive immune factors implicated Possible viral/other trigger stimulates monocyte activation Activated monocytes infiltrate adventitia of large arteries and recruit further monocytes/lymphocytes Macrophages migrate to media and produce cytokines and growth factors responsible for damage to elastic lamina and intimal hyperplasia Figure 1 Pathogenetic mechanisms operating in GCA Salvarani, C. et al. (2012) Clinical features of polymyalgia rheumatica and giant cell arteritis Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2012.97 Pathology Affects extracranial branches of carotid artery All layers of arterial wall involved Inflammatory lesions contain activated T cells dendritic cells macrophages giant cell cells Pathology Clinical features Classic features related to artery involvement - extracranial branches of carotid artery Headache -Sudden, severe, predominantly temporal -May affect occipital, parietal, frontal areas -often severe enough to disturb sleep Clinical features Jaw claudication Occurs in 40-50% patients Highly specific Needs to be distinguished from jaw pain , TMJ dysfunction and trismus Occasionally patients have intermittent claudication affecting tongue, swallowing muscles Temporal artery abnormalities Decreased or absent pulses Tenderness Thickening Nodules Redness Clinical features Scalp tenderness -occurs in 30-50% Worse with brushing/combing hair Occasional patients develop scalp necrosis Scalp necrosis in giant cell arteritis. Mackie S L , and Pease C T Postgrad Med J 2013;89:284292 Clinic features Constitutional symptoms fever, night sweats, weakness, weight loss Less commonly seen compared to pre-steroid era Patients with constitutional symptoms and high infl markers may be less likely to develop ischemic manifestations Ophthalmic complications Frequency of occurrence Opthalmology studies: 50% of patients Rheumatology studies: 20-30% of patients Ophthalmic complications Anterior ischemic optic neuritis Most common cause visual loss Due to interruption of flow in posterior ciliary arteries Presents as sudden painless visual loss May present as mist in VF progressing to blindness in 2448 hrs Unilat visual loss may initially be missed by patient May progress to contralat eye in 1-10 days Ophthalmic complications Other causes of visual loss Central retinal art occlusion Ischaemic retrobulbar neuropathy Occipital infarction Ophthalmic complications Amaurosis fugax -2-30% patients -Best clinical predictor of visual loss Diplopia -ischemia of oculomotor nerve -occurs in 5-6% patient Ness, T; Bley, T A; Schmidt, W A; Lamprecht, P The Diagnosis and Treatment of Giant Cell Arteritis Dtsch Arztebl Int 2013; 110(21): 376-86; DOI: 10.3238/arztebl.2013.0376 Clinical features Large vessel involvement Distal ischemia Limb claudication Vascular bruits May present as PUO Aortic involvement possibly more common than recognised -risk of aortic rupture/dilatation Clinical features Neurological manifestations CVA Mononeuropathies/polyneuropathies(rare) Clinical features Resp tract symptoms (often missed) Cough Sore throat Hoarseness Clinical features Audiovestibular dysfunction Facial pain Facial swelling Odontogenic pain Glossitis Carotidodynia Investigations Elevated ESR/CRP/PV Inflammatory markers usually abnormal Usual to check both CRP and ESR (or PV) Investigations High fibrinogen/haptoglobin Thrombocytosis Anemia of chronic disease Elevated alkaline phosphatase Anticardiolipin antibodies Temporal artery biopsy Considered Gold Standard Recommended length > 2 cm False neg -Sampling error -missed areas of inflammation -Skipped lesions -Arteritis limited to great arteries Biopsy should be done preferably before treatment Or soon as possible after starting treatment if required Temporal artery biopsy What is a positive biopsy? -Transmural changes only -What about adventitial changes only? -“Healed” arteritis? possible confusion with age related changes Bilateral biopsies? Temporal artery biopsy Temporal artery biopsy Temporal artery biopsy Imaging High resolution colour doppler US Can visualise both lumen and vessel wall Vessel wall features of presumed inflammation - Seen as hypoechogenic mural thickening -”halo” Dependent on equipment, operator NB “halo” reported in normal patient, PAN Imaging Other features stenoses, occlusions Sensitivity 88%, Specificity 78% Precise role still not clearly defined Figure 3 Ultrasonographical findings for GCA Salvarani, C. et al. (2012) Clinical features of polymyalgia rheumatica and giant cell arteritis Nat. Rev. Rheumatol. doi:10.1038/nrrheum.2012.97 a & b = normal artery c & d= temporal arteritis MRI Can demonstrate mural inflammatory enhancement Role in diagnosis? Temporal artery involvement Small studies: Sens 89-94%, Specificity 92-100% May be useful for assessing large vessels Role in monitoring? C+D= Biopsy proven Giant Cell arteritis Bley et al AJNR October 2007 28: 1722-1727 A 62-yr-old female patient with histologically validated GCA. Transverse contrastenhanced, fat-suppressed, T1-weighted SE image at initial presentation (A) and after 10 months of corticosteroid treatment (C). Bley T A et al. Rheumatology 2008;47:65-67 PET-CT Useful modality for assessing extent of disease involvement May demonstrate subclinical vasculitis of great vessels May provide information about response to treatment Can only evaluate large arteries Clinical utility still unclear Patient presenting with PUO Mimics/differentials Herpes zoster Cluster headache Migraine Cervical spondylosis Basal skull lesions Sinus disease Infiltrative retro orbital Temporomandibular joint lesions TIA pain Ear problems CTD Other systemic vasculitides Classification criteria Age at onset>50yrs New headache Temporal artery abnormality Elevated ESR >50 (Westergren method) Abnormal artery biopsy Three or more features yield Sensitivity 93.5% Specificity 91.2% Limited applicability in daily practice Predictors of neuro ophthalmic complications/positive TAB biopsy History Jaw claudication Diplopia Physical exam TA beading TA prominence TA tenderness Treatment Recommended starting regimens Uncomplicated GCA -no visual symptoms -no jaw claudication Start Prednisolone 40-60mg Treatment Complicated evolving visual loss or hx amaurosis fugax IV methylpred 500mg-1g daily for three days Then Prednisolone 60mg daily Treatment Other issues Bone protection Bisphosphonate/calcium/vitamin D supplementation PPI Aspirin 75mg daily Tapering 40-60mg prednisolone (not <0.75 mg/kg) continued for 4 weeks (until resolution of symptoms and laboratory abnormalities) Then dose is reduced by 10mg every 2 weeks to 20 mg Then by 2.5mg every 2- 4 weeks to 10 mg Then by 1mg every 1-2 months provided there is no relapse Monitoring Frequency: Suggested review at Weeks 0, 1, 3, 6 then months 3, 6, 9, 12 in the first year Features: Headaches Jaw and tongue claudication Visual symptoms. Vascular claudication of limbs, bruits, pulses Blood pressure Proximal pain and morning stiffness. Disability related to GCA. Monitoring Full blood count, ESR/CRP, urea and electrolytes, glucose Every two yrs-CXR(?) Bone mineral density Management of relapse Headache: treat with the previous higher glucocorticosteroid dosage Headache and jaw claudication: treat with 60mg prednisolone Eye symptoms: treat with either 60mg prednisolone or IV methylprednisolone Steroid sparing agents Limited evidence Consider if recurrent relapses or difficulty reducing steroid dose Methotrexate Tocilizumab small case series/case reports of efficacy Cyclophosphamide Complications/prognosis Generally runs self limited course Overall survival similar to general population Permanent partial/complete loss of vision in 15-20% Inc risk CV events inc MI, CVA & PVD Risk aortic dilatation/aneurysmal rupture Polymyalgia rheumatica Highest incidence in Northern Europeans & people of Scandinavian ancestry 2-3 times more common than GCA Occurs in 50% patients with GCA 5-30 % of patients with PMR may develop GCA Some pathogenetic similarity to GCA Polymyalgia rheumatica Presentation with pain and stiffness of neck. Shoulder girdle and pelvic girdle usually at least 4 weeks duration May be abrupt in onset Symptoms and signs of systemic inflammation Malaise, weight loss, low grade fever, swats Elevated CRP/ESR. Up to 20% may have normal ESR Clinical features Up to 50% distal MSK features Mild distal synovitis, bursitis Occasionally swelling/pitting edema of hands, wrists Carpal tunnel syndrome Subjective weakness Constitutional symptoms Investigations Elevated CRP &/or ESR(PV) Nonspecific abnormalities in other tests Anemia, elevated alkaline phosphatase US & MRI can demonstrate bursitis and synovitis PET CT may demonstrate subclinical vasculitis Differentials Rheumatoid arthritis Inflammatory myositis Remitting Seronegative Fibromyalgia Symmetrical Synovitis with Pitting Edema Multifocal MSK problems Bone disease Hypothyroidism Parkinson’s disease PMR treatment Dramatically responsive to steroids Most response to Prednisolone <20mg/day Dose gradually tapered Tapering an art not science! Monitor for relapse, features of GCA ,side-effects of GC Steroid sparing Mostly conflicting and inconclusive data Options tried include Methotrexate Biologics (anti-TNF agents) Azathioprine Summary GCA & PMR are closely related disorders affecting middle aged/older people Unknown cause but genetic and enviromental factors influence pathogenesis GCA primarily affects aorta and extracranial branches In GCA biopsy is important in confirming diagnosis GC are cornerstone of treatment Significant associated morbidity Some patients have chronic course and require GC for several yrs Questions/comments? Question Jaw claudication A. is pathognomonic of GCA B. is defined by pain on chewing C. signifies extensive involvement of branches of the external carotid artery D. is classified as an ischaemic feature of GCA E. is never due to atherosclerosis alone S. Mackie and C Pease. Postgrad Med J 2013;89:284-292 Question In the diagnosis of GCA A. The American College of Rheumatology criteria are useful diagnostic criteria in clinical practice. B. Ophthalmological evaluation is necessary in the presence of visual manifestations C. Pain on opening the mouth is one of the typical ischaemic manifestations of GCA D. Jaw claudication is never caused by atherosclerosis E. Aortic imaging should be routinely performed S. Mackie and C Pease. Postgrad Med J 2013;89:284-292 Thank you