GOUT AND PSEUDOGOUT

Prof Zay
CRYSTAL-ASSOCIATED ARTHRITIS AND
DEPOSITION IN CONNECTIVE TISSUE
Crystal
Monosodium urate monohydrate
Calcium pyrophosphate dihydrate
Basic calcium phosphates
Cholesterol
Calcium oxalate
Association
Acute gout  
Chronic tophaceous gout
Acute 'pseudogout'  
Chronic (pyrophosphate)
arthropathy  
Chondrocalcinosis
Calcific periarthritis  
Calcinosis
Chronic effusions in RA
Acute arthritis in dialysis patients
 Definition

• It is a syndrome caused by the inflammatory

reaction of the joint or periarticular tissues to
the presence of monosodium urate
monohydrate (MSUM) crystals
 Classification

• Acute gout.
• Tophaceus Gout.
• Asymptomatic Hyperuricemia.
• Primary Gout.
• Secondary Gout.
 Asymptomatic hyperuricemia
• Clinical laboratories define hyperuricemia as >
8-8.5 mg/dl
• In physiologic terms , any levels > 6.8 mg/dl
because it exceeds the soluble concentration
of MSU in body fluid
• Incidence of gout increases with age as well as
degree of hyperuricemia
• However vast majority of people with
hyperuricemia never develop symptoms
associated with uric acid excess .
 Diminished renal excretion
• Inherited isolated renal tubular defect ('under-excretors')Renal
failure, Chronic drug therapy, Thiazide and loop diuretics
• Low-dose aspirin
• Ciclosporin
• Pyrazinamide
• Lead toxicity (e.g. in 'moonshine' drinkers)Lactic acidosis
(alcohol)
 Increased production of uric acid
• Increased purine turnover
– Chronic myeloproliferative or lymphoproliferative disorders
(e.g. polycythaemia, chronic lymphatic leukaemia)
• Increased de novo synthesis ('over-producers')
– Unidentified abnormality (most common)
– Specific enzyme defect (rare)
– Hypoxanthine-guanine phosphoribosyl transferase
deficiency
– Phosphoribosyl pyrophosphate synthetase over-activity
– Glucose-6-phosphatase deficiency
 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.
 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.
 Epidemiology

• 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.
 Epidemiolgy- secondary gout
• Excessive dietary purine intake,
• increase nucleotide turnover (e.g., lymphoproliferative
disorders, hemolytic anemia, psoriasis),
• Glycogen storage diseases,
• diminished renal function,
• ketoacidosis,
• lactic acidosis,
• hyperparathyroidsm
• medications.
 Clinical Manifestations

• Acute gout: acute arthritis is the most

common manifestation.
• 50% of patients experience their first attack in
this joint.
• 80% of the attacks are monoarticular and
typically involve the lower extremities. (MTP’s,
ankle and knee).
 SITES OF ACUTE GOUT

• 80% of gout patients

involve 1st MTP joint
 Clinical Manifestations
• 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.
 Clinical manifestations
• Repeated attacks could cause joint erosions.
• Polyarticular attacks are common in patients
with established poor controlled disease.
• These attacks could also involve periarticular
structures.
 Clinical Manifestations
• 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.
 Clinical Manifestations
• 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

• Solid urate deposits

in tissues
 Clinical Manifestations
• Tophi 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.
CHRONIC GOUT
 Clinical Manifestations
• 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).
 Clinical Manifestations
• 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.
 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.
 Synovial Fluid Findings

• Needle shaped
crystals of
monosodium urate
monohydrate that
have been engulfed
by neutrophils
 SYNOVIAL FLUID ANALYSIS (Polarized Light
Microscopy)
• The Gold standard

• Crystals intracellular during attacks

• Needle & rod shapes

• Strong negative birefringence

SYNOVIAL FLUID
 Diagnostic Tests
• 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 and
other crystalline arthropathies.
• Chronic tophaceus gout: Rheumatoid Arthritis,
Pseudogout, seronegative
spondyloarthropathies and erosive
osteoarthritis.
 Therapy
• Usually there is no justification for treatment
of asymptomatic hyperuricemia. But some
physicians treat if serum uric acid is > 12
mg/dl and there is risk of nephrolithiasis.
• In the setting of malignancy, when tumor lysis
can cause hyperuricemia, allopurinol is
recommended.
 Therapy
• Acute Gout: NSAID’s, corticosteroids or oral
colchicine can be used.
• NSAID’s are the preferred modality.
• When NSAID’s are contraindicated,
corticosteroids are effective.
 Therapy
• Intra-articular corticosteroids are an
alternative when systemic therapy is
contraindicated.
• Colchicine has been the medication
traditionally used for acute gout, but it has
significant GI toxicity and delayed onset of
action.
 Therapy
• Although a very high purine diet (large amounts of
seafood, red meat and offal) should be tempered,
there is no need for a specific highly restrictive diet.
• Indications for pharmacological therapy includes:
inability to reverse secondary causes, tophaceus gout,
recurrent acute gout and nephrolithiasis.
 Therapy
• The pharmacological agents indicated for gout
include: uricosuric (probenecid, sulfinpyrazone)
or inhibitors of uric acid production
(allopurinol).
• Uricosuric agents are indicated in patients with
normal renal function, under-excretion and no
evidence of tophi.
• Patients taking uricosuric agents are at risk for
urolithiasis.
 Therapy
• Allopurinol decreases uric acid in
overproducers and underexcreters; it is also
indicated in patients with a history of
urolithiasis, tophaceus gout, renal insufficiency
and in prophylaxis of tumor lysis syndrome.
• Febuxostat is a xanthine oxidase inhibitor that
is useful in patients who fail to respond
adequately to allopurinol
 Newer Therapies
• Uricase
– Enzyme that oxidizes uric acid to a more soluble form
– Natural Uricase from Aspergillus flavus and Candida utilis under
investigation
• Febuxostat
– New class of Xanthine Oxidase inhibitor
– More selective than allopurinol
– Little dependence on renal excretion
• Losartan
– ARB given as 50mg/dL can be urisuric. When given with HCTZ, it
can blunt the effect of the diuretic and potentiate its antihypertensive
action
• Fenofibrate
– Studies note when used in combo with Allopurinol produced
additional lowering of the urate
• Pegloticase is a biological treatment in which
the enzyme uricase has been conjugated to
monomethoxypolyethylene glycol. It is
indicated for the treatment of tophaceous
gout resistant to standard therapy and is
administered as an intravenous infusion every
2 weeks for up to 6 months.
 PSEUDOGOUT
• Calcium pyrophosphate Crystal Deposition
Disease (CPPD) is the syndrome secondary to
the calcium pyrophosphate crystal deposition
in articular tissues.
– Acute 'pseudogout'  
– Chronic (pyrophosphate) arthropathy  
– Chondrocalcinosis
 Pseudogout
• Etiology: It is unknown, but can be secondary
to changes in the cartilage matrix or
secondary to elevated levels of calcium or
inorganic pyrophosphate.
• Pathology: CPPD crystals are found in the
joint capsule and fibrocartilaginous structures.
There is neutrophil infiltration and erosions.
 Pseudogout
• Disease Associations: (7 Hs)
• hyperthyroidsm
• hypothyroidsm
• hypocalciuria
• hypercalcemia
• hemochromatosis
• hemosiderosis
• hypophosphatasia
• hypomagnesemia
 Gout vs. CPPD

• Similar Acute attacks

• Different crystals under Micro;

Rhomboid, irregular in CPPD
Gout vs CPPD
 Pseudogout
• Demographics: It is predominantly a disease
of the elderly, peak age 65 to 75 years old. It
has female predominance (F:M, 2-7:1).
• Prevalence of chondrocalcinosis is 5 to 8% in
the general population.
 Pseudogout
• 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.
 Psedogout
• Chronic CPPD: predominately affects women;
it is a progressive, often symmetric,
polyarthritis.
• Usually affects the knees, wrists, 2nd and 3rd
MCP’s, hips, spine, shoulders, elbows and
ankles.
 Pseudogout
• Chondrocalcinosis: Generally is an incidental
finding in XRays.
• Diagnostic Tests: Inflammatory cell count in
the synovial fluid. Rhomboidal or rodlike
intracellular crystals. Imaging studies reveal
chondrocalcinosis usually in the knee, but can
be seen in the radial joint, symphisis pubis and
intervertebral discs.
 Pseudogout
• Differential Diagnosis: Includes septic arthritis,
gout, inflammatory OA, Rheumatoid Arthritis,
neuropathic arthritis and Hypertrofic
Osteoarthropathy.
 Pseudogout
• 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.
Thank you