This document discusses gout and pseudogout. It defines gout as a crystal-induced arthropathy caused by urate crystals depositing in tissues. It discusses the epidemiology, classification, etiology, pathogenesis, clinical manifestations, diagnosis and treatment of both gout and pseudogout. Key points include that gout is more common in men and involves the lower extremities, while pseudogout predominantly affects the elderly and can resemble gout but is caused by calcium pyrophosphate crystal deposition. Treatment involves medications to reduce uric acid levels for gout and typically focuses on relieving symptoms for pseudogout.

1. GOUT AND PSEUDOGOUT
-MANOJIT SARKAR
FINAL PROF
MALDA MEDICAL COLLEGE AND HOSPITAL

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

3. 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.

4. • 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.

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

6. 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

7. 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.

8. Drugs commonly associated with
hyperuricaemia
• Cyclosporine
• Alcohol
• Nicotinic acid
• Thiazide
• Loop diuretics
• Ethambutol
• Aspirin
• Pyrazinamide

9. 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

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

11. Causes of secondary gout
Decreased excretion :
Renal-CRF,ADPKD,Lead nephropathy
Endocrine -hypothtroid,hyperparathyroid,DI
Metabolic- ketoacidosis, lactic acidosis,
stavation, severe dehydration
drugs
Misc-sarcoidosis,down syndrome

12. 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).

13. 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.

14. 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.

15. 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.

16. • 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

17. • 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

21. 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.

22. 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.

23. • 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.

25. 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.

26. 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

27. 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

28. 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

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

30. 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.

31. 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.

32. 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.

33. URICOLYTIC Drugs:rasburicase,pegloticase
• Recombinant uricase like action that convert
urate to more soluble allantoin.
• Used in resistant cases

34. 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).

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

36. 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.

37. 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

38. 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 .

39. 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.