CRYSTAL ARTHRITIS( gout and pseudogout )

Abdul Waris

Dept: internal medicine

DEFINITION/EPIDEMIOLOGY

Gout : is a painful and potentially destructive rheumatic disorder arising in the setting ofHyperuricemia and sodium urate crystals.

DEFINITION/EPIDEMIOLOGYGOUT

The prevalence of gout is increasing mainly in developed Countries

The prevalence is 1.4% in the UK and 2.7% in the USA.their diet becomes more Western.

Gout develops in men more than women (10 : 1)

Some 85–90% of cases are idiopathic.

Asian populations are more at risk as

Urate is the end product of purinemetabolism that occurs in liver

URAT1 and GLUT9, are membersof the organic acid transporterfamily and have predominanteffects on serum urate level.

AETIOLOGYGOUT:

URATE IMBALANCE >>>>>

RISK FACTORSGOUTDietary influences

Chemical composition (Total caloric intake , Triglycerides , Carbohydrates ,Protein

Specific food examples (Red meat , Beer, Liver , Shellfish etc.. )

Associated with lower urate level (Dairy products Vitamin C )

Clinical associations

Age

Male or postmenopausal female gender

Direct causal link ( such as genetic diseases or autoimmune diseases etc..)

etc..)

Associated disorders ( hypertension , hypothyroidism , obesity, renal impairment etc.. )

Acute precipitants ( trauma, surgery , dehydration , shellfish binges etc..)

Drugs

Aspirin , Diuretics, losartan, levodopa , cyclosporine etc..

Alcohol

CLINICAL MANIFESTATIONS

GOUT

Gout is presented in three main stages:

1- Asymptomatic hyperuricemia

2-acute intermittent gout

3-advanced gout

DIFFERENTIAL DIAGNOSIS

INVESTIGATION

GOUT :

The clinical picture is often diagnostic.

1-

2-

3-

Joint fluid microscopy is the most specific and diagnostic test but is technically

Serum uric acid is usually raised (>600 μmol/L)

difficult.

Serum urea, creatinine and eGFR are monitored for signs of renal impairment.

Needle-shaped urate crystals

MANAGEMENTThe use of NSAIDs or coxibs in high doses rapidly reduces the pain and swelling. The firstdose should be taken at the first indication of an attack:

1-

2-

3-

4-

5-

Naproxen-750 mg immediately, then 500 mg every 8–12 hoursDiclofenac-75–100 mg immediately, then 50 mg every 6–8 hoursIndometacin-75 mg immediately, then 50 mg every 6–8 hoursColchicine- 1000 μg immediately, then 500 μg every 6–12 hoursCorticosteroids- oral prednisolone or intramuscular or intra-articular depot methylprednisolone.

Treatment with agents that reduce serum uric acid levels:

The aim of treatment is to reduce the uric acid level below the 360 μmol/L level; someguidelines recommend below 300 μmol/L.

Allopurinol, Febuxostat , Pegloticase, Uricosuric agents, Losartan, Anakinra

Allopurinol:-

Should only be used when the attacks are frequent and severe , associated with renal impairment or tophi, or when the patient finds NSAIDs or colchicine difficult to tolerate.

Allopurinol (300– 600 mg) blocks the enzyme xanthine oxidase, which convertsxanthine into uric acid .

It reduces serum uric acid levels rapidly and is relatively non-toxic but shouldbe used at low doses (50–100 mg) in renal impairment.

Skin rashes and gastrointestinal intolerance are the most common side-effects. A hypersensitivity reaction is the most serious adverse event. This is rare, as is bone marrow suppression.

Febuxostat (80–120 mg)

Is a non-purine analogue inhibitor of xanthine oxidase but not other enzymes in the purine and pyrimidine pathway.

It is well tolerated and as effective as allopurinol in trials and is safer in renal impairment as it is metabolized in the liver and not renally excreted.

It has been approved by the FDA and is helpful in patients who cannot tolerate allopurinol but there are anxieties that it may increase cardiovascular risks.

At time of writing, most doctors advise trying allopurinol first unless there are strong contraindications to its use.

Pegloticase

a pegylated recombinant uricase given intravenously, lowers urate levels dramatically but its place in therapy is unclear.

Uricosuric agents

also lower the serum uric acid but their use is restricted throughout Europe by the very rare occurrence of serious hepatotoxicity.

Benzbromarone acts on theURAT-1 transporter and is well tolerated.

Sulphinpyrazone and probenecid are best avoided in renal impairment.

Losartanis an angiotensin I-receptor antagonist and is uricosuricin hypertensive patients with gout. I

t may reduce the risk of gout in patients with the metabolic syndrome.

Anakinra

blocks IL-1β and canakinumab is a human monoclonal antibody with specific cross-reactivity for IL-1β but not other members of the IL-1 family.

Their role in treatment-resistant gout is still subject to trials to establish when their use is justified in gout which has not responded to the more conventional agents.

Pseudogout

Precipitation of crystals of calcium pyrophosphate dihydrate (CPPD) inconnective tissues which may be asymptomatic or may be associatedwith several clinical syndromes

CLINICAL MANIFESTATIONS

Pseudogout (pyrophosphate arthropathy)

Calcium pyrophosphate deposits in hyaline and fibrocartilage produce the radiological appearance of chondrocalcinosis.

Shedding of crystals into a joint precipitates acute synovitis which resembles gout, except that it is morecommon in elderly women and usually affects the knee or wrist.

The attacks are often very painful.

In young people it may be associated with haemochromatosis, hyperparathyroidism, or Wilson's disease.

INVESTIGATIONPSEUDOGOUT

Central investigations for diagnosis are

1-

2-

fluid and tissue analysis for

plain radiographs.

the presence of CPP crystals

Rhomboid shaped crystal

Treatment

Aspiration of the joint reduces the pain dramatically but it is usually necessary to use an NSAID or colchicine, as for gout.

If infection can be excluded, an intra-articular injection of a corticosteroid helps.

REFERENCESKumar & Clark’s clinical medicine 8th edition

Harrison, Tinsley Randolph, and Anthony S. Fauci. Harrison's principles of internal medicine. 14th ed.New York: McGraw-Hill, Health Professions Division, 1998. Print.

Hochberg, Marc C.. Rheumatology. 5th ed. Philadelphia: Mosby/Elsevier, 2011. Print.