Polymyalgia rheumatica and giant cell arteritis
Download
1 / 57

Polymyalgia Rheumatica and Giant Cell Arteritis - PowerPoint PPT Presentation


  • 340 Views
  • Uploaded on

Polymyalgia Rheumatica and Giant Cell Arteritis. History of PMR and GCA. First description: 940-1010 BC Treatment was removal of affected artery English literature Bruce (1888) PMR – “senile rheumatic gout” Hutchinson (1890) – provided description of GCA Horton (1932)

loader
I am the owner, or an agent authorized to act on behalf of the owner, of the copyrighted work described.
capcha
Download Presentation

PowerPoint Slideshow about 'Polymyalgia Rheumatica and Giant Cell Arteritis' - conner


An Image/Link below is provided (as is) to download presentation

Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author.While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server.


- - - - - - - - - - - - - - - - - - - - - - - - - - E N D - - - - - - - - - - - - - - - - - - - - - - - - - -
Presentation Transcript

History of pmr and gca
History of PMR and GCA

  • First description: 940-1010 BC

    • Treatment was removal of affected artery

  • English literature

    • Bruce (1888) PMR – “senile rheumatic gout”

    • Hutchinson (1890) – provided description of GCA

  • Horton (1932)

    • Classic histology findings

    • Coined “giant cell arteritis”

  • Barber (1957)

    • Coined “polymyalgia rheumatica”


Pathogenesis
Pathogenesis

  • Genetic predisposition influenced by exposures

  • Increased incidence @ higher latitudes

    • Scandinavian background

    • Occasional familial cases

  • Initiating viral pathogen?

    • Parainfluenza virus type1

    • Mycoplasma

    • Parvovirus


Genetics of pmr and gca
Genetics of PMR and GCA

  • HLA-DRB1*01 and *04

    • Associated w/ susceptibility to GCA/PMR

    • Rheumatoid Arthritis

  • Mutually exclusive populations

    • Different part of genes involved in each condition


Common pathogenesis of pmr and gca
Common Pathogenesis of PMR and GCA

  • Activated circulating monocytes

  • Inflammatory cytokine production

  • Th1 response in vessel wall

  • No autoantibody component

NEJM 2003;349(2): 160-169.


Pathogenesis of gca
Pathogenesis of GCA

  • A: Activation of Dendritic cells

  • B: Oxidative damage by macrophages

  • C, D: Differential expression of VEGF and PDGF

NEJM 2003;349: 160-169.


Relation of pmr to gca
Relation of PMR to GCA

  • PMR seen in 40-50% of pts w/ GCA

  • About 15% of PMR pts develop GCA

  • Some view PMR as forme fruste GCA

    • Vasculitis remains subclinical


Epidemiology of pmr
Epidemiology of PMR

  • Prevalence: 3300 per 100,000

  • Incidence

    • Scandinavian/N. European: 50-68/100,000

    • Spain, Italy: 12-18 per 100,000

  • Women > Men, about 3:1

  • Highly unlikely in those < age 50

  • Mean age at onset is 70

Gonzalez-Gay et al. Arthritis Rheum 2009;61:1454-1461


Polymyalgia rheumatica pmr
Polymyalgia Rheumatica (PMR)

  • Clinical syndrome

    • Seen in “elderly” patients

    • Characterized by pain/stiffness (> 4 wks)

    • Involves neck, shoulder initially then hip region

    • Constitutional symptoms common

    • Laboratory evidence of systemic inflammation

      • ESR, CRP, anemia


Other pmr features
Other PMR Features

  • Fever/chills

    • GCA, infection, malignancy

  • Arthritis / joint inflammation

    • Non-erosive synovitis


Arthritis in pmr
Arthritis in PMR

NEJM 2002; 347, 261-278.


Diagnosis of pmr
Diagnosis of PMR

  • Compatible clinical syndrome

  • Exclusion of diff dx

  • Elevated acute phase response

  • Response to corticosteroids

NEJM 2002; 347:261-278.


Differential diagnosis pmr
Differential Diagnosis - PMR

RS3PE – Remitting Symmetric Synovitis with Pitting Edema


Pmr and malignancy
PMR and Malignancy

  • No excess malignancy in PMR

  • Consider paraneoplastic PMR-like syndrome

    • Poor or incomplete response to steroids

    • Young age

    • Relatively low ESR

  • Most common malignancies

    • Colon, Lung, Kidney, Leukemia, Lymphoma

  • Without findings suggestive of cancer ensure age-appropriate screening is current


Treatment of pmr steroids
Treatment of PMR: Steroids

  • Very responsive to oral steroids: 10 – 20 mg daily

  • What is best initial dose?

    • Ann Rheum Dis 1989;48:658-661.

  • Average duration of steroid therapy 2 years

    • Prevention of bone loss

  • Gradually taper steroids

    • Some patients require low dose prednisone

    • ? Role of steroid sparing agents

  • Monitor for relapses

    • Clinical features > labs


Sample steroid taper for pmr
Sample Steroid Taper for PMR

  • Start 20 mg daily for 4 weeks

  • Decrease by 2.5 mg daily every 2-4 weeks to 10 mg daily

  • From 10 mg daily decrease by 1 mg daily every 2-4 weeks

  • For relapse return to higher dose


Methotrexate for pmr
Methotrexate for PMR

  • Limitations of trials

    • Few patients

    • Varying steroid and methotrexate doses

    • Short duration

  • Prior negative studies

    • Feinberg et al. J Rheum 1996;23(9):1550-1552.

      • Open-controlled; 12.5mg/wk not steroid sparing

    • Van der Veen et al. Annals Rheum Dis 1996;55:218-223.

      • RDBPC; 7.5 mg/week not steroid sparing


Methotrexate for pmr1
Methotrexate for PMR

  • Two positive trials

    • Ferraccioli et al.J Rheum 1996 ;23(4):624-628.

      • Open, randomized; 10 mg methotrexate IM weekly

      • Total steroid dose reduced at 1 year

    • Caporali et al. Ann Intern Med 2004;141:493-500.

      • RDBPC; 10 mg methotrexate po weekly; 72 patients

      • 25 mg prednisone both arms

      • Shorter prednisone treatment / lower dose in MTX arm

      • High starting dose prednisone (25 mg daily)

      • High weekly folinic acid supplement (7.5 mg weekly)


Other steroid sparing drugs in pmr
Other “Steroid Sparing” Drugs in PMR

  • Azathioprine

    • De Silva et al. Ann Rheum Dis 1986 Feb;45(2):136-138.

    • 31 patients, 100-150 mg / day azathioprine

    • Steroid sparing effect seen at 1 year

  • Anti-TNF

    • Enbrel: Catanoso et al.Arthritis Rheum. 2007 Dec 15;57(8):1514-9.

    • Open case series 6 patients, steroid dependent PMR

    • 24 weeks treatment, 36 weeks follow-up

    • Significant reduction in steroid dose

    • Infliximab: Salvarani et al. J Rheumatol. 2003 Apr;30(4):760-3.

    • 3 of 4 patients had clinical response sustained at 1 year


Epidemiology gca
Epidemiology - GCA

  • Age >50 years (mean 70)

    • Incidence increases progressively w/ age

    • Most common vasculitis in northen hemisphere

  • Gender

    • Women > men about 2:1

  • Population prevalence (Age 50 or older)

    • Scandinavian/N. European: 22-76/100K

    • Spain, Israel: 10 per 100K

    • France, Italy: 6.9-9.4 per 100K

    • Shelby Co, TN: 2.2 Cauc., 0.4 AA per 100K


Synonyms of gca
Synonyms of GCA

  • Temporal arteritis

  • Cranial arteritis

  • Granulomatous arteritis

  • Horton’s headache


Gca classification criteria
GCA: Classification Criteria

NEJM 2002; 347, 261-278.


Presentations of gca
Presentations of GCA

  • Cranial Arteritis

  • Headaches

  • Ischemic Optic Neuropathy

  • Jaw Claudication

  • PMR

  • Fever/Wasting Syndrome

  • Fever and chills

  • Anorexia, weight loss

  • Night sweats

  • Weakness

  • Depression

GCA

PMR

Syndrome

  • Large-vessel GCA/aortitis

  • Arm claudication

  • Pulselessness

  • Raynaud’s phenomenon

  • Aortic aneurysm

  • Aortic insufficiency

  • PMR

  • Isolated PMR

  • Pelvic girdle muscles

  • Pain in shoulder and

  • Stiffness


Cranial arteritis symptoms
Cranial Arteritis - Symptoms

  • Headache – 2/3 of patients

    • Throbbing, sharp or dull

    • Usually severe, seek medical attention

  • Scalp tenderness

    • Usually over temporal artery

    • Wearing glasses, grooming, lying down

  • Jaw/tongue claudication – up to 50% of patients

    • Masseter/temporalis muscles

    • Painful dysphagia


Eye symptoms in gca
Eye symptoms in GCA

  • Various presentations

    • Diplopia

    • Amaurosis fugax

    • Scotoma

    • Ptosis

    • Partial or complete blindness

  • Above can be transient or permanent

  • Permanent partial/complete blindness

    • 15 to 20% of patients in most literature


Gca other symptoms
GCA – Other Symptoms

  • Musculoskeletal complaints are common

    • PMR (40%)

    • Peripheral arthritis

    • Swelling and pitting edema

  • Arm claudication

    • 10-25% patients

    • Bruits

    • Diminished neck or arm pulses


Gca other symptoms1
GCA – Other Symptoms

  • CNS events – 20 to 30% of patients

    • TIA or CVA

    • Carotid/vertebrobasilar

    • Neuropathy

  • Pulmonary – up to 25%

    • Cough, hoarseness, chest pain

    • Pulmonary hemorrhage (case report)


Gca as an fuo
GCA as an FUO

  • Subset of patients with:

    • Systemic inflammatory syndrome

    • Malaise, anorexia, weakness

    • Fatigue, wasting, depression

  • Physical exam not consistent with:

    • Cranial arteritis

    • Large vessel occlusive disease

    • PMR


Large vessel gca
Large-vessel GCA

  • 10-15% of patients

  • Targets aortic branches

    • Carotid, subclavian, axillary arteries

  • Aortic arch syndrome

    • Claudication of arms

    • Absent/asymmetrical pulses

    • Parasthesias, Raynaud’s phenomenon

    • Occasional peripheral gangrene


Large vessel gca1
Large-vessel GCA

  • Often without cranial arteritis

    • No headaches, other cranial symptoms

    • Normal temporal artery exam

    • 50% of temporal artery biopsies negative



Temporal arteries
Temporal Arteries

  • Thickened, tender and nodular

    • Occasionally erythematous

    • Pulses reduced or absent

    • 1/3 of patients, temporal arteries grossly normal

  • Other external carotid branches

    • Occipital/superficial scalp vessels


Cranial arteritis and the eye
Cranial arteritis and the eye

  • Ophthalmologic emergency

    • Prompt treatment can prevent blindness

  • Ischemic optic neuropathy

    • Most common cause of visual loss


Causes of visual loss in gca
Causes of visual loss in GCA

% of 63

Patients

AION – anterior ischemic optic neuropathy BRAO – branch retinal artery occlusion

PION – posterior ischemic optic neuropathy CI – choroidal infarct

CRAO – central retinal artery occlusion OA – optic atrophy (unclear etiology)

Liu et al. Ophthalmology 1994;101:1779-1785.


Other exam findings
Other Exam Findings

  • Vascular bruits

    • Carotid, Subclavian, Axillary

  • Differential BP between arms

  • Diminished pulses


Laboratory features of gca
Laboratory Features of GCA

  • Elevated ESR, CRP

    • Up to 23% with normal ESR at diagnosis

  • Elevated IL-6

    • Highest sensitivity for ongoing disease

    • Both before/after corticosteroid therapy

  • Anemia of chronic disease

  • Elevated platelet count

  • Elevated alkaline phosphatase


Differential diagnosis gca
Differential Diagnosis – GCA

  • Other vasculitis or pseudovasculitis

  • Vascular headache/migraine

  • Infections (acute sinusitis)

  • Hypothyroidism

  • Neoplastic / paraneoplastic process

    • Multiple myeloma, leukemia, lymphoma

  • Joint disease (OA, RA)

  • PM/DM, other myositis


Making the diagnosis of gca
Making the Diagnosis of GCA

  • Compatible clinical syndrome

  • Exclusion of differential diagnosis

  • Look for physical exam clues

  • Majority have dramatic acute phase response

  • Superficial temporal artery

    • Easiest site to biopsy

    • Most useful for intermediate pre-test probability

  • False negative biopsies can occur:

    • Take a sufficient length of biopsy (5 cm)

    • Examine serial sections

    • Consider contralateral bx if 1st is negative

    • Limit time of treatment prior to biospy


Utility of signs and symptoms in suspected giant cell arteritis
Utility of Signs and Symptoms in Suspected Giant-Cell Arteritis

Weyand, C. M. et. al. Ann Intern Med 2003;139:505-515.


Timing of temporal artery biopsy
Timing of Temporal Artery Biopsy Arteritis

  • Ray-Chaudhuri et al.Br J Ophth 2002; 86: 530-532.

    • Prospective study of 11 patients

    • All met ACR criteria for GCA (before bx)

    • All started on steroids at time of dx

    • 9/11 - Positive biopsies overall

    • 6/7 - Biopsy (+) 4-6 wks after steroids

  • Narvaez et al.Semin Arthritis Rheum. 2007 Aug;37(1):13-9.

    • 35/45 biopsies (+) within 2 weeks

    • 13/20 biopsies (+) 2-4 weeks

    • 2/5 biopsies (+) 4 weeks or more


Histopathology
Histopathology Arteritis

  • 50% have pan-arteritis with giant cell formation, often in close proximity to disrupted elastic lamina

  • Large and medium arteries

  • Involvement is focal and segmental


Giant-Cell Arteritis of the Temporal Artery Arteritis

Weyand C and Goronzy J. N Engl J Med 2003;349:160-169


Adjunctive diagnostic tools
Adjunctive Diagnostic Tools Arteritis

  • Ultrasound

    • “Dark halo” around temporal artery

  • Results of 86 patients (U/S then bx)

    • Any halo, 40% sens and 79% spec

    • 1mm or >, 40% sens and 93% spec

  • Conclusion

    • Only modest predictor of positive biopsy

    • Did not improve dx accuracy of PE

Salvarani et al. Annals 2002;137: 232-238.



Other diagnostic tools
Other Diagnostic Tools Arteritis

If extracranial GCA suspected, may consider:

  • Angiography

    • Document disease of large arteries

  • MRA

    • Useful for diagnosis

      • Rheumatology (Oxford). 2005 Apr;44(4):479-83.

    • May improve finding of vasculitis in FUO

      • Annals Rheum Dis. 2005 Jan;64(1):105-10 .


Large vessel gca2
Large Vessel GCA Arteritis

  • Tapering of L maxillary artery

  • Aneurysm of ascending aorta

  • Dilation and thickening of descending aorta


Pet scan and gca
PET Scan and GCA Arteritis

  • Vascular FDG uptake at diagnosis

    • 29 of 35 patients (83%)

    • Most common in subclavian vessels (74%)

    • Aorta 51% thoracic and 54% abdominal

  • Not predictive of relapse

    Blockmans et al. Arthritis Rheum 2006;55(1):131-137.


Gca treatment
GCA Treatment Arteritis

  • Corticosteroids

    • Initiate promptly to avoid visual loss

    • Start with 40-60 mg/day of prednisone (1mg/kg)

      • Single or divided doses

    • Recent visual loss

      • Hospitalize for IV methylprednisolone

      • Pulse dose qday or divided q6h

  • Aspirin reduces stroke

    • 2 retrospective studies (341 patients total)

      • Arthritis Rheum. 2004 Apr;50(4):1332-7. NNT = 5.

      • Arthritis Rheum. 2006 Oct;54(10):3306-9. NNT = 3.


Gca treatment corticosteroids
GCA Treatment - Corticosteroids Arteritis

  • Ideally, continue 40-60 mg prednisone until:

    • Remission of possibly reversible symptoms

    • Laboratory values are normal

    • Usually, 2 to 4 weeks

  • Reduce dose by about 10% every 1-2 weeks

  • Symptoms, then ESR/CRP guide taper

  • Alternate-day steroids unsuccessful

  • Conflicting data on steroid-sparing agents

  • Expected Response

    • Rapid resolution within a few days

    • Lack of improvement should prompt consideration of other diagnosis


Relapse in gca
Relapse in GCA Arteritis

  • Common

  • Treat on clinical grounds

  • ESR/CRP - may not increase

  • Dosage of steroid with relapse

    • Return to dose prior to onset of symptoms

    • Some may need chronic low-dose steroid


Methotrexate in gca
Methotrexate in GCA Arteritis

  • Hoffman et al. Arthritis Rheum. 2002 May;46(5):1309-18.

    • No benefit of adding methotrexate to steroids

  • Jover et al. Ann Intern Med 2001;134:106-114.

    • MTX + corticosteroids > corticosteroids alone

    • 42 patients, 21 per group

    • > or = 1 relapse: 45% vs. 84% (NNT 3)

    • > or = 2 relapses: 10% vs. 47% (NNT 3)

  • Spiera et al. Clin Exp Rheumatol 2001 Sep Oct;19(5):495-501.

    • No benefit of adding MTX to corticosteroids


Methotrexate meta analysis
Methotrexate Meta-Analysis Arteritis

  • Arthritis Rheum. 2007 Aug;56(8):2789-97.

    • Performed by many of prior authors

    • Individual patient data meta-analysis

    • 84 pts got MTX, 77 got steroids only

    • Follow-up 54 weeks

  • Main result: MTX appeared helpful

    • NNT for 1st / 2nd relapse 3.6 / 4.7

    • Total steroid dose reduced by 842 mg


Azathioprine tnf agents
Azathioprine & TNF agents Arteritis

  • Azathioprine

    • Double-blind, placebo-controlled trial

    • Mean dose of 1.5-2.7 mg/kg/day

    • Difference in mean dose of prednisolone

    • Significance not reached until 52 weeks

  • Infliximab

    • Few successful case reports

  • Etanercept – 1 successful case report

De Silva M et al. Ann Rheum Dis 1986 Feb;45(2).

Cantini et al. A&R 2001:44(12); 2933-35.

Tan. Ann Rheum Dis 2003; 62(4): 373-4.


Key points pmr
Key Points: PMR Arteritis

  • Diagnose PMR

    • Elderly patient, often female

    • Neck, shoulder, hip pain and stiffness

    • Exclusion of other causes

    • Elevated ESR, CRP

    • Anemia of chronic disease

  • Treat PMR

    • Initial Prednisone dose 10 – 20 mg

    • Dramatic response by 2-3 days

    • Taper prednisone slowly and increase if needed based on symptoms

    • Prevent steroid related bone loss


Key points gca
Key Points: GCA Arteritis

  • Manage giant cell arteritis

    • Compatible clinical picture

    • Look for PE clues

    • Lab findings: ESR, CRP, Anemia, Alk Phos

    • If suspected don’t delay treatment for biopsy

      • Contact Ophthalmology for biopsy

    • Start with high dose steroids

      • 60 mg prednisone, higher if visual loss present

    • Aspirin reduces stroke in GCA


ad