Rheumatology - For BPTs

Dr Leanne Alblas

2nd year Rheumatology trainee

Rheumatology for BPTs An introduction

Acknowledgment to Dr Claire Owen for many of the slides

Outline PMR and GCA

Monoarthritis

Polyarthritis

Back pain – Inflammatory vs. Mechanical

PMR and GCA

A 75-year-old woman is evaluated for a sudden loss of vision in the left eye that began 30

minutes ago. She has a 2-week history of fatigue; malaise; and pain in the shoulders, neck, hips,

and lower back. She also has a 5-day history of mild bitemporal headache.

On physical examination, temperature is 37.3 °C (99.1 °F), blood pressure is 140/85 mm Hg,

pulse rate is 72/min, and respiration rate is 16/min. BMI is 31. The left temporal artery is tender.

Fundoscopic examination reveals a pale, swollen optic disc. Range of motion of the shoulders

and hips elicits moderate pain.

Laboratory studies:

Hemoglobin 9.9 g/dL (99 g/L)

Leukocyte count 7300/µL (7.3 × 109/L)

Platelet count 456,000/µL (456 × 109/L)

Erythrocyte sedimentation rate 116 mm/h

Which of the following is the most appropriate next step in this patient’s management?

A) Brain MRI

B) High-dose intravenous methylprednisolone

C) Low-dose oral prednisolone

D) Temporal artery biopsy

Previous Exam Question GCA vs PMR

Previous Exam Question GCA Which of the following clinical features confers the highest likelihood for the presence of Giant Cell Arteritis?

A. Diplopia

B. Headache

C. Jaw Claudication

D. Large Joint Synovitis

E. Proximal Myalgia

Polymyalgia Rheumatica Polymyalgia Rheumatica (PMR) is a chronic,

inflammatory disorder of unknown cause

Characterised by sudden-onset shoulder and pelvic girdle pain, and prolonged early morning stiffness

Affects men and women over the age of 50 years

Most common inflammatory rheumatic disease of the elderly: Ranks second only to Rheumatoid Arthritis in terms of lifetime

incidence risk (2.43% for women and 1.66% for men)

Kermani, TA (2013). ‘Polymyalgia rheumatica’. Lancet; 381:63-72.

Crowson, CS et al. (2011). ‘The lifetime risk of ault-onset rheumatoid arthritis and other inflammatory autoimmune rheumatic diseases’. Arthritis &

Rheumatism;63(3):633-9.

Polymyalgia Rheumatica

Salvarani, C. et al. ‘Clinical features of polymyalgia rheumatica and giant cell arteritis’. Nature Reviews Rheumatology;8(9):509-21.

Figure 1: Typical sites of pain in patients with PMR. Shaded areas demonstrate the distribution in the a) shoulder and b) pelvic girdle.

Polymyalgia Rheumatica Heterogeneity in the clinical features and disease

course is well recognised:

Distal manifestations eg. Synovitis, tenosynovitis, pitting oedema, carpal tunnel syndrome (~50%)

GCA (16-21%): Up to 50% of GCA diagnoses have musculoskeletal symptoms

consistent with PMR

Polymyalgic-onset Rheumatoid Arthritis and spondyloarthritis

Dasgupta, B et al (2012). ‘Provisional classification criteria for polymyalgia rheumatica: a EULAR/ACR collaborative initiative’. Arthritis &

Rheumatism; 64(4):943-54.

Salvarini, C et al. ‘Polymyalgia rheumatica and giant cell arteritis’. Lancet; 372(9634):234-45.

Polymyalgia Rheumatica

Bilateral subacromial bursitis is the hallmark lesion of PMR on imaging:

Sensitivity 92.9%, specificity 99.1%

Ultrasound:

Preferred imaging technique

Findings of biceps tenosynovitis and trochanteric bursitis are similarly consistent with PMR

Camellino, D et al. (2012). ‘Imaging of polymyalgia rheumatica: indications on its pathogenesis, diagnosis and prognosis’. Rheumatology; 51(1):77-86.

Polymyalgia Rheumatica Diagnosis is based upon a clinical construct and raised

inflammatory markers:

Dasgupta, B et al (2012). ‘Provisional classification criteria for polymyalgia rheumatica: a EULAR/ACR collaborative initiative’. Arthritis &

Rheumatism; 64(4):943-54.

Polymyalgia Rheumatica Glucocorticoids remain the mainstay of treatment

The British Society for Rheumatology Guidelines for Management of PMR represent a recently developed consensus-based regimen:

PNL 15mg daily for 3 weeks

PNL 12.5mg daily for 3 weeks

PNL 10mg daily for 4 weeks, wean by 1mg every 4 weeks thereafter

The role of steroid-sparing agents is unclear

Dasgupta, B et al. (2010). BSR and BHPR guidelines for the management of polymyalgia rheumatica. Rheumatology;49(1):186-90.

Kermani, TA (2013). ‘Polymyalgia rheumatica’. Lancet, 381:63-72.

Giant Cell Arteritis Also known as Temporal Arteritis

Giant Cell Arteritis (GCA) is a large-vessel vasculitis with a predilection for the aorta and its branches

The aetiology is unknown

Characterised by temporal headache (80%), scalp tenderness and jaw claudication

Most common vasculitis in men and women over 50 years of age


GCA: history & examination features

1. Smetana GW, Shmerling RH. Does this patient have temporal arteritis? JAMA 2002;287:92–101

Giant Cell Arteritis Ischaemic events are the most feared complication:

Anterior Ischaemic Optic Neuropathy (up to 20%)

Stroke (rare)

Long-term, GCA patients can develop large vessel aneurysms or stenosis


Figure 3: Stenosis of the left subclavian artery on MRA in a GCA patient.

Giant Cell Arteritis Temporal artery biopsy is the diagnostic gold

standard:

Sensitivity ranges from ~70% to >90%

Breur, GS (2009). ‘Rate of discordant findings in bilateral temporal artery biopsy to diagnose giant cell arteritis’. Journal of Rheumatology; 36(4): 794.

Hunder, GG et al. (1990). ‘The American College of Rheumatology 1990 criteria for the classification of giant cell arteritis’. Arthritis & Rheumatism;

33:1122-8.

Giant Cell Arteritis

American College of Rheumatology (2014). Available from: http://images.rheumatology.org

Figure 4: Temporal artery biopsy demonstrating segmental destruction of internal elastic lamina and granulomatous vessel inflammation with giant cells.

http://images.rheumatology.org/

Giant Cell Arteritis The lack of a non-invasive diagnostic tool has

promoted the use of imaging modalities

Ultrasound:

Arterial wall oedema, seen as the halo sign, can be demonstrated in some patients with GCA: Sensitivity 42%, specificity 94%

Black, R et al (2013). ‘The use of temporal artery ultrasound in the diagnosis of giant cell arteritis in routine practice’. International Journal of

Rheumatic Diseases; 16:352-7.

Figure 5: Colour duplex ultrasound demonstrating the halo sign.

Giant Cell Arteritis Treatment should not be withheld prior to temporal

artery biopsy

Glucocorticoids similarly remain the mainstay of treatment:

Uncomplicated GCA (no visual loss) – PNL 50mg daily

Evolving visual loss – Methylprednisolone 1g IV for 3 consecutive days

Aspirin is also recommended in all patients with GCA without a major contraindication

Ghosh, P et al. (2010). ‘Current understanding and management of giant cell arteritis and polymyalgia rheumatica’. Expert Review Clinical

Immunology; 6(6): 913-28.

Giant Cell Arteritis A steroid-sparing agent should be considered

following recurrent relapse or failure to wean PNL

Ghosh, P et al. (2010). ‘Current understanding and management of giant cell arteritis and polymyalgia rheumatica’. Expert Review Clinical

Immunology; 6(6): 913-28.

Take Home Message

Condition Manifestations Investigations When to Refer

Giant Cell Arteritis • Temporal headache

• Scalp tenderness • Jaw claudication • Visual loss

• CRP – elevated • ESR – elevated • Temporal artery

biopsy

Immediately

Monoarthritis

Previous Exam Question Monoarthritis

A 78-year-old man with a 15-year history of osteoarthritis is evaluated for severe pain and swelling of the left knee of 4 days' duration. He also has hypertension, type 2 diabetes mellitus, and chronic kidney disease. Medications are glyburide, lisinopril, and low-dose aspirin. On physical examination, vital signs are normal. He is unable to bear weight on the left leg because of pain. The left knee is swollen and warm, and range of motion of this joint is limited and elicits pain. There are no tophi. Laboratory studies reveal leukocyte count 15,600/µL (15.6 × 109/L) (90% polymorphonuclear cells, 10% lymphocytes), glucose (random) 210 mg/dL (11.7 mmol/L), serum creatinine 2.2 mg/dL (167.9 µmol/L), serum uric acid 10.7 mg/dL (0.63 mmol/L) and normal urinalysis. Arthrocentesis of the left knee is performed. Synovial fluid leukocyte count is 24,000/µL (90% polymorphonuclear cells, 10% lymphocytes). Polarized light microscopy reveals intra- and extracellular monosodium urate crystals. Gram stain is negative. Q: Which of the following is the most appropriate treatment for this patient?

A. Allopurinol

B. Colchicine

C. Ibuprofen

D. Intra-articular methylprednisolone

E. Prednisone

Septic arthritis

Haemarthroses

Crystal arthritis: Gout

Pseudogout

“BBC”- Bugs, Blood, Crystals

DDx of acute monoarthritis

Acute Monoarthritis Can be the initial manifestation of many joint

disorders

Chokkalingam, S et al. (2003). ‘Diagnosing acute monoarthritis in adults: a practical approach for the family physician’. American Family Physician;

68(1):83-90.

Acute Monoarthritis Can be the initial manifestation of many joint

disorders


68(1):83-90.

Acute Monoarthritis Arriving at the correct diagnosis is crucial for

appropriate treatment

Serious management errors can arise from:

Failing to perform a joint aspirate

Starting treatment before aspirating the joint

Basing a diagnosis purely on laboratory results eg. Serum urate level


68(1):83-90.

Synovial Fluid Analysis

Lingling, M et al. (2009). ‘Acute monoarthritis: what is the cause of my patient’s painful swollen joint?’. CMAJ; 180(1):59-65.

Septic Arthritis Acute joint infection

Staphylococcus aureus is the most common organism

Risk factors include:

Age >80 years

Diabetes mellitus

Rheumatoid arthritis

Recent joint surgery

Hip or knee prosthesis

Skin infection


Septic Arthritis Characterised by joint pain (85%), swelling (78%)

and limited range of motion

Fever may be absent (sensitivity 57%)

A synovial fluid leucocyte count >50000/mm3 is the most useful finding in making an early diagnosis:

Positive likelihood ratio 7.7 (CI 5.7 – 11.0)

Rapidly progressive joint destruction is seen on plain x-ray in untreated cases

Gout and sepsis may co-exist

Margaretten, ME et al. (2007). ‘Does this adult patient have septic arthritis?. JAMA; 297:1478-88.

Zhang, W et al (2006). ‘EULAR evidence based recommendations for gout: part 1: diagnosis.’ Annals of Rheumatic Disease; 65:1301-11.

Past Exam Question RA and septic arthritis Which of the following DMARDs is most likely to increase risk of septic arthritis in patients with Rheumatoid Arthritis?

A. Corticosteroids

B. Etanercept

C. Leflunomide

D. Methotrexate

E. Sulfasalazine

Infection Risk in Rheumatology Inflammatory conditions increase susceptibility to

infection due to: Underlying immune modulation of the disease process

Frequent use of glucocorticoids and immunosuppressive therapies

Prednisolone is associated with one of the highest overall infection risks

Most evidence suggests a neutral effect of synthetic DMARDs

Infection risk with TNF inhibitors is highest at commencement (RR 4.6 in first 90 days)

Gout Monosodium urate deposition in peri-articular soft

tissues

Risk factors include: Male sex

Diabetes mellitus

Hypertension

Obesity

Cardiovascular disease

Chronic renal failure

Diuretic use

Purine-rich diet

Alcohol consumption


Metabolic syndrome

Past Exam Question Purine metabolism QUESTION 16 What is the most common mechanism for primary hyperuricaemia? A. Increased gastrointestinal absorption of uric acid B. Increased cell turnover C. Inherited defects in purine synthesis D. Inherited defects in adenosine triphosphate (ATP) metabolism E. Reduced uric acid urinary excretion

Past Exam Question Purine metabolism QUESTION 16 What is the most common mechanism for primary hyperuricaemia? A. Increased gastrointestinal absorption of uric acid B. Increased cell turnover C. Inherited defects in purine synthesis D. Inherited defects in adenosine triphosphate (ATP) metabolism E. Reduced uric acid urinary excretion

Gout If polyarticular, typically asymmetrical in

distribution

Tophi have high clinical diagnostic value: Positive likelihood ratio 40.0 (95% CI 21.1-75.8)

The serum urate level neither confirms nor excludes the diagnosis

Needle-like, negatively birefringent crystals are seen on synovial fluid analysis


Figure 8: Tophi seen in the helices of the ear.

Gout Long-term, plain x-ray changes include juxta-

articular “punched-out” erosions


Figure 9: A gouty erosion seen along the medial margin of the first metatarsal head.

Past Exam Question Gout Treatment 62 yo man with hx of gout presents with acute painful arthritis of his 1st right MTP joint. He has mild renal impairment Cr. 136. What is the best treatment option?

A. NSAID's

B. Allopurinol

C. Colchicine

D. Probenecid

E. Corticosteroids

Gout Management of an acute attack: NEVER stop prophylaxis

Non-pharmacologic: ~15% decrease in serum urate level

Dietary modification (alcohol, purine-rich foods, fructose)

Weight loss and exercise (metabolic syndrome)

Pharmacologic:

Young and eGFR >50ml/min – NSAIDs

Elderly and eGFR >50ml/min – Colchicine 500mcg BD

Elderly and eGFR <50ml/min – Prednisolone Monoarticular (not MTP) – intra-articular corticosteroid

Polyarticular – PNL 25-30mg

Gout Prophylaxis: Indications:

Recurrent attacks

Tophi

Erosive change on plain x-ray

Nephrolithiasis

Commence 1-2 weeks after acute attack (consider ongoing medication)

Review every month and “treat to target” – serum urate level <0.36

Allopurinol

(Uricosuric agents eg. Probenicid)

Febuxostat (xanthine oxidase inhibitor)

Pseudogout Calcium pyrophosphate dihydrate crystal

deposition disease

Typically affects the knee and wrist joints

Risk factors include: OA

Hypercalcaemia

Hyperparathyroidism

Hypomagnesaemia

Hypothyroidism

Haemochromatosis


Past Exam Question CPPD distribution QUESTION 37

Which of the these joints is most likely to be involved in pseudogout (calcium pyrophosphate deposition disease)?

A. Ankle

B. Knee

C. 1st Metacarpophalangeal

D. 1st Carpometacarpal

E. Wrist

Past Exam Question CPPD distribution QUESTION 37

Which of the these joints is most likely to be involved in pseudogout (calcium pyrophosphate deposition disease)?

A. Ankle

B. Knee

C. 1st Metacarpophalangeal

D. 1st Carpometacarpal

E. Wrist

Pseudogout Rhomboid, positively birefringent crystals are seen

on synovial fluid analysis

Chondrocalcinosis may be seen on plain x-ray:


Figure 10: Calcification of the menisci and articular cartilage that is typical of chondrocalcinosis.

Pseudogout Management of an acute attack:

Young and eGFR >50ml/min – NSAIDs

Elderly and eGFR >50ml/min – Colchicine 500mcg BD

Elderly and eGFR <50ml/min – Prednisolone

Take Home Message


Acute Monoarthritis • Joint pain • Joint swelling • Limited range of

movement

• Joint aspirate • Blood cultures

Immediately

Polyarthritis

Rheumatoid Arthritis Chronic autoimmune disease that causes

inflammation and deformity of the joints

Prevalence 1%, twice as common in women as men

Precise aetiology remains unknown

Smoking is the best defined risk factor

Timely diagnosis is critical to prevent uncontrolled disease leading to irreversible joint damage

Ngian, G. (2010). ‘Rheumatoid arthritis’. Australian Family Physician; 39(9):626-628.

Rheumatoid Arthritis Typically, characterised by a symmetrical arthritis

affecting the wrists and, metacarpophalangeal and proximal interphalangeal joints of the hands

ESR and CRP are usually elevated at diagnosis and correlate with disease activity and treatment response

Testing for both rheumatoid factor and anti-CCP is

recommended


Rheumatoid Arthritis

Aletaha, D et al. (2010). ‘2010 Rheumatoid Arthritis Classification Criteria’. Arthritis & Rheumatism; 62(9):2569-81.

Rheumatoid Factor

• About 1% of the normal population has a detectable rheumatoid factor

In Rheumatoid Arthritis (RA), 70% of patients are rheumatoid factor positive:

Sensitivity 70%, specificity 85%

Its role in the pathogenesis of RA is unknown

Persistent high-titre rheumatoid factor predicts more severe disease

Karsten, K et al (2010). ‘Profiling of rheumatoid arthritis associated auto-antibodies’, Autoimmunity Reviews; 9:431-5.

Anti-Citrullinated Peptide Antibodies

Pathogenic auto-antibodies of RA

Similar sensitivity to rheumatoid factor, but superior specificity: Sensitivity 70%, specificity 95%

Detected in sera of patients years before symptom onset

Best prognostic indicator for erosive RA

Karsten, K et al (2010). ‘Profiling of rheumatoid arthritis associated auto-antibodies’, Autoimmunity Reviews; 9:431-5.

Anti-Nuclear Antibody

13-25% of the normal population have a

detectable ANA, 2.5% at high titre

Found in both systemic and organ-specific

autoimmune disease eg. Graves’ disease (50%)

Pattern correlates poorly with diagnoses, except

anti-centromere

If high titre, also check eNA and dsDNA

Satoh M. et al (2012). ‘Prevalence and sociodemographic correlates of antinuclear antibodies in the United States’. Arthritis and

Rheumatism;10:1002/art.34380.

Anti-Nuclear Antibody

Referrals to a tertiary centre Rheumatology Clinic for positive ANA: 232 patients

2.1% had Systemic Lupus Erythematosus, 9.1% had other ANA associated disease

No disease identified in patients with ANA <1:160

Abeles, A.M. & Abeles, M. (2013). ‘The clinical utility of a positive Antinuclear Antibody Test Result’. The American Journal of

Medicine’ : 126:342-8.

Rheumatoid Arthritis Rather than relying on surrogate markers of

inflammation, imaging is increasingly being utilised to assess disease activity

Plain x-ray: Historical gold standard of erosion assessment

Marginal erosions, peri-articular osteopaenia and joint space narrowing are classic features

X-Rays are abnormal at presentation in only 15-30% RA patients

Most useful for monitoring progression of joint damage over time

Yearly repetition is common practice

McQueen, F (2013). ‘Imaging in early rheumatoid arthritis’, Best Practice and Research Clinical Rheumatology; 27:499-522.


American College of Rheumatology (2014). Available from: http://images.rheumatology.org

Figure 11: Typical plain x-ray changes in RA including marginal erosions, peri-articular osteopaenia and joint space narrowing.

http://images.rheumatology.org/

Rheumatoid Arthritis Ultrasound:

Visualises both inflammatory disease activity and structural joint damage

Greyscale synovitis correlates highly with DAS28 and radiographic progression at 1 year

Detects 6.5-fold more erosions in early disease compared with plain x-ray

Power Doppler signal predicts clinical relapse (OR 6.3 95% CI 2.0-20.3)

Thiele, RG (2012). ‘Ultrasonography applications in diagnosis and management of early rheumatoid arthritis’, Rheumatic

Diseases Clinics of North America; 38:259-75.


MRI: Ideally suited to image bony structures and cartilage,

as well as soft tissues and fluid

Detects erosions involving <20% bone volume loss of metacarpal head

Unique capacity to image bone marrow oedema

In undifferentiated arthritis, predicts RA onset with sensitivity of 100% and specificity of 78%

Availability, cost and contraindications problematic

McQueen, F (2013). ‘Imaging in early rheumatoid arthritis’, Best Practice and Research Clinical Rheumatology; 27:499-522.


Aggressive treatment to achieve clinical remission is imperative: Symptomatic: Simple analgesia

NSAIDs/omega 3 fatty acids

Low-dose glucocorticoids eg. PNL 15mg daily

Disease modifying agents: Methotrexate

Combination DMARD therapy eg. MTX + HCQ + SSZ

Biologics eg. TNF inhibitors


Take Home Message


Inflammatory Polyarthritis

• Joint pain • Joint swelling • Extended early

morning stiffness

• ESR – elevated • CRP – elevated • Rheumatoid

factor • Anti-CCP • ANA

• Plain x-ray hands

Urgent outpatient referral

Back pain: Inflammatory vs. Mechanical

Past Exam Question An 18 year old has a two year history of recurrent swelling of the knees and ankles which usually settles after 1-2 weeks. They have also had intermittent crampy abdominal pain and diarrhoea for the last 6 months. The timing of the arthritis and diarrhoea do not appear to be related. Which test is most likely to make the diagnosis?

A. Colonoscopy

B. HLA-B27

C. Plain XR of the joints

D. Rheumatoid factor

E. Stool culture

Back pain features: Inflammatory vs. Mechanical

Golder, V & Schachna, L (2013). ‘Ankylosing spondylitis: an update’. Australian Family Physician; 42(11):780-4.

Spondyloarthritis Encompasses a group of rheumatic disorders that

share clinical, genetic and radiographic features


Ankylosing Spondylitis Chronic inflammatory condition of the sacroiliac

joints and spine

Affects 1 in 200 individuals

Male:female ratio 2:1

Extra-axial features include peripheral arthritis (up to 50%), enthesitis, dactylitis and anterior uveitis (40%)

Reduced spinal mobility is seen on examination

The delay between symptom onset and physician

Ankylosing Spondylitis

ESR and CRP are elevated in only 50-70% of cases

HLA-B27: Between 5-15% of the general population are HLA-

B27 positive, but only 5% of these develop AS

In AS patients, HLA-B27 occurs in 85-90%

Consequently, HLA-B27 has no role as a general screening test for spinal pain


Ankylosing Spondylitis Diagnosis requires inflammatory back pain and

changes on plain x-ray of the pelvis


Figure 13: Radiographic grading of sacroiliac joints.

Non-Radiographic Axial SpA Early presentation of AS,

prior to plain x-ray changes

50% of patients will evolve into AS


Ankylosing Spondylitis A tailored exercise and stretching program is

recommended

NSAIDs are first-line therapy for symptomatic AS

Traditional DMARDs play no role in axial disease

TNF inhibitors can be initiated in patients with an inadequate response to NSAIDs


Case 4 Management?

Tailored exercise and stretching program: www.nass.co.uk/exercise

Celecoxib 200mg daily

Semi-urgent outpatient Rheumatology referral Axial involvement non-responsive to above:

TNFi incl. Golimumab, Humira, Infliximab

Non-axial involvement

Methotrexate, Sulfasalazine

http://www.nass.co.uk/exercise

Past Exam Question A 23 yo male presents with 1 week of arthralgias and 2 days of arthritis of the left wrist and right knee. On examination there is tenosynovitis of the extensor tendons of the left forearm, and a pustular rash on the palm of his left hand. The most likely diagnosis is:

A. Ankylosing Spondylitis

B. Enteropathic arthritis

C. Gonococcal arthritis

D. Psoriatic arthritis

E. Reactive arthritis

Take Home Message


Inflammatory Low Back Pain

• Low back pain • Extended early

morning stiffness

• Peripheral arthritis

• Enthesitis • Dactylitis • Anterior uveitis*

• ESR – ?elevated • CRP – ?elevated

• Plain x-ray pelvis

• HLA-B27

Semi-urgent outpatient referral

Thank-you! Questions?

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Rheumatology - For BPTs

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