GOUT AND PSEUDOGOUT

-MANOJIT SARKARFINAL PROF

MALDA MEDICAL COLLEGE AND HOSPITAL

Definition

• Gout is the most common crystal induced arthropathy & is caused by the inflammatory response to tissue deposition of monosodium urate crystals (MSU).

Epidemiology

• The prevalence of asymptomatic hyperuricemia is 5 to 8%.

• The prevalence of gout is 13 cases per 1000 men and 6.4 cases per 1000 women.

• The higher the uric acid, the higher the risk to develop gout.

• 90% of patients with primary gout are men.

• Women rarely develop gout before the menopause, because estrogens are thought to be uricosuric.

• Peak incidence in men is in the fifth decade.• Primary gout is associated with: obesity,

hyperlipidemia, diabetes mellitus, hypertension and atherosclerosis.

Classification

4clinical stages:• Asymptomatic Hyperuricemia.• Acute gout.• Intercritical phase• Chronic Tophaceus Gout.

Etiology

• Hyperuricemia is the common denominator in gout.

• Two-thirds of uric acid are excreted by the kidney and the rest in the GI tract.

• 90% of cases of gout are secondary to under-excretion.

• Overproduction is secondary to defects in the HGPRT or PRPP

Pathogenesis

• The inflammatory response is secondary to the response of the leukocytes to the MSU crystals.

• Acute gout is most likely secondary to the formation of new crystals.

• Factors that precipitate gout includes: surgery, trauma, alcohol, starvation and initiation or discontinuation of uric acid lowering agents & medications.

Drugs commonly associated with hyperuricaemia

• Cyclosporine • Alcohol• Nicotinic acid• Thiazide• Loop diuretics• Ethambutol• Aspirin • Pyrazinamide

Pathology

• The most frequent sites of deposition of MSU crystals are: cartilage, epiphyseal bone, periarticular structures and the kidney.

• A tophus is a foreign body reaction that includes the MSU crystals surrounded by fibrous tissue.

• In the kidney the deposition of MSU crystals causes interstitial fibrosis and arteriosclerosis

Causes of secondary gout

Increased production:• Excessive dietary purine intake,• lymphoproliferative disorders,• chronic hemolytic anemia, • Exfoliative psoriasis• Carcinomatosis or tumour lysis syndrome• alcohol.

Causes of secondary gout

Decreased excretion :Renal-CRF,ADPKD,Lead nephropathyEndocrine -hypothtroid,hyperparathyroid,DIMetabolic- ketoacidosis, lactic acidosis,

stavation, severe dehydrationdrugs Misc-sarcoidosis,down syndrome

Clinical Manifestations

• Acute gout: acute arthritis is the most common manifestation. .

• 50% of patients experience their first attack in mtp of first toe.

• 80% of the attacks are monoarticular and typically involve the lower extremities. (MTP’s, ankle and knee).

Clinical Manifestation

• Less common sites of involvement include wrist, fingers and elbow.

• Differential diagnosis includes septic arthritis, cellulitis or thromboflebitis.

• Attacks subside in 3 to 10 days.• Recurrent attacks can involve more joints and

usually persist longer.

Intercritical gout

• It is the asymptomatic period between crises, but MSU crystals can still be recovered if necessary.

• The duration of this period varies, but untreated patients may have a second episode within two years.

• Some patients evolve to chronic polyarticular gout without pain free intercritical episodes.

Chronic tophaceus Gout

• The clinical characteristic is the deposition of solid urate in the connective tissue.

• It is associated with early age of onset, long duration of untreated disease, frequent attacks, upper extremity involvement, polyarticular disease and elevated serum uric acid.

• Transplant patients treated with cyclosporine and/or diuretics have an increased risk for tophaceus gout.

• The most common sites for tophi are: the olecranon, prepatellar bursa, ulnar surface and Achilles tendon. Tophi in the hands can cause joint destruction.

• Tophi can ulcerate the skin and excrete a chalky material composed of MSU crystals.

• Tophi progress insidiously with increased stiffness and pain

• Renal disease: this includes urolithiasis, urate nephropathy (deposition of MSU crystals in the interstitium), and uric nephropathy ( deposition of MSU crystals in the collecting tubes).

• The prevalence of urolithiasis is 22% in primary gout and 42% in secondary gout.

• Uric acid nephropathy may present acutely in patients being treated for malignancy.

• Urate nephropathy is slowly progressive and associated with hypertension and proteinuria

Diagnostic Tests

• Uric Acid: normal values range from 4.0 to 8.6 mg/dl in men to 3.0 to 5.9 mg/dl in women. Urinary levels are normal below 750 mg/ 24h.

• Urinary levels above 750 mg/dl in 24h in gout or > 1100 mg/dl in asymptomatic hyperuricemia indicates urate overproduction.

Diagnostic Tests

• Joint Fluid: in acute gout it is inflammatory (>2000 cells/ml); MSU crystals are identified with the polarized light microscope. In acute gout the crystals are usually intracellular.

The MSU crystals do not exclude the possibility of septic arthritis, for this reason it is also recommended to request a Gram smear.

• 24 urine collection for uric acid determination is useful in assessing the risk of renal stones and planning for therapy.

• Radiological examination is helpful to exclude other kinds of arthritis. Long term gout shows erosive arthritis with the characteristic “punched-out” erosions.

Differential Diagnosis

• Acute Gout: septic arthritis, pseudogout, Reactive arthritis, acute rheumatic fever trauma ,hemarthrosis,tumor

• Chronic tophaceus gout: Rheumatoid Arthritis, Pseudogout, seronegative spondyloarthropathies and erosive osteoarthritis.

Therapy

Asymptomatic hyperuricemia-• Currently there is no justification for treatment of

asymptomatic hyperuricemia except 3 specific circumstances

sustained serum uric acid is > 13 mg/dl for men and>10mg/dl in women

there is risk of nephrolithiasis.(excretion of urinary uric acid >1100mg/day)

In the setting of malignancy when patient is about to receive chemo or radiotherapy that is likely to result in extensive tumor lysis

Therapy

Acute Gout: • NSAID’s- are the preferred modality.• oral colchicine • corticosteroids -when NSAID’s& colchicine are

contraindicated, • Anakinra-in resistant &rebound flares• Rilonacept & Conakinumab are in clinical trial

Therapy

Intercritical Gout: the focus in this stage is prevention and prophylaxis.

• Patients with only one or few attacks it is acceptable to wait and treat the acute attacks.

• Patient with frequent attacks(>2-3attacks per year ),clinical & radiological evidence of chronic gouty arthritis,gout with renal insufficiency,recurrent uric acid nephrolithiasis should be offered medical treatment

Serum uricacid lowering therapy:• URICOSTATIC Drugs:allopurinol,febuxostat• URICOSURIC Drugs :probenecid• URICOLYTIC Drugs:rasburicase,pegloticase

Allopurinol:xanthine oxidase inhibitor • usual dose is 300 mg/day. Maximal recommended dose is 800 mg/day.• In renal insufficiency dose should be decreased to 200 mg/day for

creatinine clearance < 60ml/min and to 100 mg/day if clearance < 30 ml/min).

• Start with small doses of allopurinol to reduce the risk of precipitating an acute gout attack.

• Most common side effects are rash (2% of patients),nausea vomitting but rarely patients can develop exfoliative dermatitis that can be lethal.

• Concominant use of colchicine (0.6-1.2 mg/day) is used as prophylaxis for acute flares.

FEBUXOSTAT:non purine xanthine oxidase inhibitor• usual dose is 40 mg/day. Maximal

recommended dose is 80 mg/day.• Extensively metabolised by liver.so no dose

reduction needed in renal impairement• Most common side effects are rash (2% of

patients),nausea vomitting & a greater incidence of LFT abnormalities.

URICOSURIC Drugs :• indicated in patients with normal renal function, under-

excretion and no evidence of tophi.Should be avoided in patient with nephrolithiasis or nephropathy

• Patients taking uricosuric agents are at risk for urolithiasis. This can be decreased by ensuring high urinary output .

• The available agents include: probenecid (1-2 g/day) and benzbromarone (25-100 mg /D).

• Losartan,fenofibrate,vit c,high dose of aspirin has mild uricosuric effect.

URICOLYTIC Drugs:rasburicase,pegloticase• Recombinant uricase like action that convert

urate to more soluble allantoin.• Used in resistant cases

CPPD Deposition diseases

• secondary to deposition ofcalcium pyrophosphate in articular tissues.

• predominantly a disease of the elderly, peak age 65 to 75 years old. It has female predominance (F:M, 2-7:1).

Disease Associations

• hyperparathyroidsm• hypocalciuria, hypercalcemia,• hemochromatosis, hemosiderosis• hypophosphatasia, hypomagnesemia• hypothyroidsm, gout, neuropathic joints• Amyloidosis• trauma • OA

Etiology

• It is unknown, but basically secondary to changes in the cartilage matrix due to elevated levels inorganic pyrophosphate decreased levels ofpyrophosphatase.

• Release of CPPD crystals in the joint capsule and fibrocartilaginous structures lead to neutrophil infiltration ,inflammatory reactions and erosions.

Clinical Manifestations

• Pseudogout: Usually presents with acute self-limited attacks resembling acute gout. The knee is involved in 50% of the cases, followed by the wrist, shoulder, ankle, and elbow.

• Chronic CPPD:mainly polyarticular Can present as induction or enhancement of peculiar form

of osteoarthritis Induction of severe destructive arthritis Production of symmetric synovitis intervertebral disk &ligament calcification Spinal stenosis

Diagnosis• Chondrocalcinosis: punctate or linear radiodense

opacities in fibocartilagineous joint menisci or in hyaline cartilage. Imaging studies reveal chondrocalcinosis usually in the knee, but can be seen in the radial joint, symphisis pubis and intervertebral discs.in absence of joint effusion synovial biopsy is needed

• Definitive diagnosis:by demonstration of typical Rhomboidal or rodlike intracellular crystals in the synovial fluid.also Inflammatory cell count is increased .

Treatment

• Therapy: It is similar to gout and includes intrarticular corticosteroids.

• Colchicine can be used in acute attacks and also in prophylaxis.

• There is no specific treatment for chronic CPPD. It is important to treat secondary causes and colchicine could be helpful.