Crystal Arthropathy and Polymyalgia Rheumatica

Question 1

What are the common crystal deposition diseases characterised by?

Answer 1

Deposition of mineralised material within the joints and periarticular tissue

Question 2

What substance is present in gout?

Answer 2

Monosodium urate

Question 3

What substance is present in pseudogout?

Answer 3

Calcium Pyrophosphated DiHydrate (CPPD)

Question 4

What substance is present in calcific periarthrtiis/tendonitis?

Answer 4

Basic calcium phosphate hydroxy-apatite (BCP)

Question 5

What is tophus?

Answer 5

Massive accumulation of uric acid

Question 6

Pathology of Lesch Nyan Syndromes

Answer 6

HGPRT deficiencies
- hypoxanthine guanine phosphonbosy transferase
- normally plays a role in recycling purine bases, hypoxanthine and guanine, into purine nucleotide pools
- in the absence of this, the purine bases are degraded and excreted as uric acid
- the synthetic rate for purines also accelerates
The failure of recycling together with increased synthesis of purines is the basis for the over production of uric acid
X linked recessive

Question 7

Features of Lesch Nyan syndromes

Answer 7

Intellectual disability
Aggressive and impulsive behaviour
self mutilation 
gout
renal disease

Question 8

Who gets pseudogout?

Answer 8

The knee is to pseudogout as the toe is to gout

Elderly females

Question 9

Causes of pseudogout

Answer 9

Idiopathic
Familial
metabolic

Question 10

Triggers of pseudogout

Answer 10

Trauma

Intercurrent illness

Question 11

Features of pseudogout

Answer 11

Erratic flares
Chondrocalcinosis
Pyrophosphate crystals

Question 12

Treatment of pseudogout

Answer 12

NSAIDs

I/A steriods

Question 13

Is there prophylactic therapy for pseudogout?

Answer 13

No

Question 14

Pathology of gout

Answer 14

Purine metabolism

• endogenous production of uric acid from degradation of purines contributes to 2/3rds of body urate pool, remainder dietary in origin
• 70% of uric acid produced is excreted by the kidneys and the rest by the biliary tract and bacteria
• in the vast majority of people with gout, HYPERURICAEMIA RESULTS FROM REDUCED EFFICIENCY OF RENAL URATE CLEARANCE

Question 15

Causes of hyperuricaemia

Answer 15

Overproduction 
- malignancy e.g. lymphoproliferative 
- severe exfoliative psoriasis
- drugs, e.g. ethanol, cytotoxic drugs 
- inborn errors of metabolism 
- HGPRT deficiency 
Underexcretion 
- renal impairment 
- hypertension 
- hypothyroidism 
- drugs e.g. alcohol, low dose aspirin, cyclosporin
- exercise
- starvation 
- dehydration 
- lead poisoning

Question 16

Why does alcohol increase the risk of gout?

Answer 16

Some alcoholic drinks are rich in purines, noteably beer
Metabolism of ethanol to acetyl CoA leads to the formation of a precursor of uric acid
Alcohol also raises the lactic acid level in the blood which inhibits the uric acid secretion

Question 17

Who gets gout?

Answer 17

Older men (men have higher urate levels than women)
Very rare in young women

Question 18

Gout and women

Answer 18

Very rare in young women as oestrogen has a uricosuric effect
after menopause, urate levels rise and gout becomes increasingly prevalent

Question 19

Ageing is a risk factor for both men and women for gout due to …..

Answer 19

Increase in sUA levels (mainly due to reduced renal function)
Increased use of diuretics and other drugs that are raised in sUA
Age related changes in connective tissues which may encourage crystal formation
Increased prevalence of OA

Question 20

Treatment of gout/hyperuricaemia

Answer 20

Acute flare of gout 
- NSAIDs
- Colchicine 
- Steroids (I/A, I/M, oral) 
Hyperuricaemia 
- prophylactically prior to treating malignancies 
- lowering uric acid
         - xanthine oxidase inbihitor (allopurinol)
         - febuxostat 
         - uricosuric agents (sulphinpyrazone)
         - canakinumab 
Lifestyle
- BP
- weight loss
- diet
- alcohol and smoking

Question 21

When is hyperuricaemia treated?

Answer 21

DO NOT TREAT IF ASYMPTOMATIC
1st attack not treated unless 
- single attack of polyarticular gout 
- tophaceous gout
- urate calculi 
- renal insufficiency 
Treat if second attack in one year

Question 22

Rules for lowering uric acid levels

Answer 22

Wait until the acute attack has settled before attempting to reduce the urate level

Use prophylactic NSAIDs or low dose colchicine/steroids until the urate level Is normal

Adjust allopurinol dose according to renal function

Question 23

What is polymyalgia rheumatica?

Answer 23

An inflammatory condition of the elderly causing pain, stiffness and inflammation of muscles around the shoulders, neck and hips

Question 24

What is polymyalgia rheumatica closely related to?

Answer 24

GCA

Question 25

Symptoms of gout

Answer 25

Sudden severe pain | Swelling, redness and tenderness over joints

Question 26

Where is gout pain often seen?

Answer 26

The base of the big toe

Question 27

Who gets polymyalgia rheumatica?

Answer 27

rare <50, usually > 70 y/o | F > M 2:1

Question 28

Presentation of polymyalgia rheumatica

Answer 28

``` Rapid onset < 1 month SUDDEN onset of shoulder +/- pelvic girdle stiffness Aching, morning stiffness in proximal limbs (NOT weakness) ESR usually > 45 often 100 Anaemia Malaise Weight loss Fever Night sweats Depression ```

Question 29

Diagnosis of polymyalgia rheumatica

Answer 29

``` Compatible history Age > 50 ESR > 50 Dramatic steroid response *no specific diagnostic test* ```

Question 30

Differential diagnosis for polymyalgia rheumatica

Answer 30

``` Myalgic onset inflammatory disease underlying malignancy - multiple myeloma - lung cancer Inflammatory muscle disease Hypo/hyperthyroidism Bilateral shoulder capsulitis Fibromyalgia ```

Question 31

Treatment of polymyalgia rheumatica

Answer 31

Prednisolone 15mg per day daily 18-24 month course | Bone prophylaxis

Question 32

Where is most commonly affected in pseudogout?

Answer 32

Knee Wrist Shoulder

Question 33

How does colchicine work?

Answer 33

Inhibits microtubule polymerisation by binding to tubulin, interfering with mitosis. Also inhibits neutrophil motility and activity

Question 34

Classic side effect of colchicine

Answer 34

Diarrhoea

Question 35

What does polymyalgia rheumatica NOT have?

Answer 35

Weakness

Question 36

What are chemo patients at increased risk of and why?

Answer 36

Gout | Increased urate production

Question 37

What should happen to allopurinol treatment if they are already on the treatment, but have an acute flare of gout?

Answer 37

Continue allopurinol on current dose

Question 38

RFs for pseudogout

Answer 38

``` Hyperparathyroidism Hemochromatosis Acromegaly Low Magnesium Low phosphate Wilsons disease ```

Question 39

What is seen on joint aspiration if have pseudogout?

Answer 39

Weakly-positively birefringent rhomboid-shaped crystals