Gout is characterized by an altered purine metabolism with deposition of uric acid salts in connective tissues such as cartilage (of joints or of the ears), the walls of bursa and ligaments.
Exact etiology not known
Hereditary predisposition postulated
Any rapid change in uric acid can precipitate acute gouty attack.
Primary gout: This can be due to overproduction or underexcretion. a. Underexcretors: Decreased excretion of uric acid by the kidneys b. Overproducers: Increased production of uric acid
Secondary gout: This is acquired from underlying conditions such as polycythemia, multiple myeloma or sickle cell or other haemoglobinopathies.
The total body urate pool is the net result between urate production & excertion.
Pathophysiology of acute gout attack:
Tophus: The pathognomic tissue lesion of gout is the tophus. The tophus is a mass of crystalline or amorphous urates surrounded by an intense inflammatory reaction of macrophages, lymphocytes and fibroblasts as large foreign body type giant cells.
More commonly in in males above 40 years of age & in postmenopausal females.
Arthritis: Acute onset pain, erythema, edema & stiffness of joints involving mainly peripheral joints (such as toes, tarsus, ankle & hands) called PODAGRA. First metatarsophalangeal joints is often the first joint to be affected because of repeated exposures to microtrauma & a lower temperature compared to body temperature.
Bursitis: Most commonly olecranon bursa is affected & it becomes distended with fluid, there may be palpable deposits ot uric acid salts.
Nodules at ligamentum patella & ear cartilage due to gouty tophi deposition.
Renal invlovement: Three types of lesions may be seen. 1. Urate Nephropathy: It results from the deposition of crystals in the medullary interstitium, the pyramids & papillae. 2. Acute Obstructive Renal Failure: It results from intratubular deposition of free uric acid crystals. There cases are more common in secondary gout due to chemotherapy or in myeloproliferative disorder. 3. Uric acid stone formation is common in patients excreting more than 1100 mg of uric acid per day.
Palms of hands may show white streaks along the creases (plasterer's hand).
Soft tissue swelling around the joint.
'C' shaped punched out lesions in subchondral region with sclerotic base.
Irregular soft tissue densities due to tophaceous deposits.
Role of laboratory studies in DID of crystalline arthropathies:
The joint aspiration must be done & synovial fluid sent for following analysis:
Cell count & Differential: A WBC count < 50,000 cells/mm is more suggestive of crystalline arthropathy. WBC count more than that does not rule out gout.
Crystal Analysis under polarized microscopy: This is a definitive diagnostic tests for determining appropriate crystal (monosodium urate in acute gouty arthritis & calcium pyrophosphate in acute pseudogout).
Gram stain, routine culture & sensitivity.
Acute gouty arthritis:
Acute seronegative inflammatory arthritis
Chronic tophaceous gout:
Nodular Rheumatoid Arthritis
Recurrent attacks occur with normal joint between the acute attacks which last for few days. In cases of chronic gout the affected joints are severely disorganized.
Relieve the signs & symptoms of acute attack
Reduce uric acid levels
Reduce & if possible, eliminate the factors that produce gout
Patient is placed on absolute bed rest.
Immobilization of affected limb is done. Local cold or heat therapy may be used.
Adequate fluid intake, diet inclusive of glycine & rich in carbohydrate is advised.
Alcohol must be avoided.
Drugs commonly used in acute gout attacks are:
Colchicine: Oral or intravcl10us
NSAIDS ( Indomethacin, Naproxen are most commonly used)
Mode of action:
I. It inhibits the phagocytosis of urate crystals by neutrophils.
II. It interferes with transport of phagocytosed materials to the lysosomes.
III. It's interference with chemotactive response is believed to reduce joint inflammation.
Dosage and administration: It is generally administered as 1 mg orally as an initial dose, followed by 0.5 mg every 2 hours until gastrointestinal discomfort or diarrhea develops or until a total dose of 8 mg has been given. Relief of clinical signs & symptoms is usually reached within 2 days.
Alternatively it may be given as an IV initial dose of 2 mg followed by two separate doses of 1 mg at 6 hours interval, with total dose not exceeding 4 mg with the first 24 hours.
Precautions: The dose should be halved in the elderly & in patients with renal & hepatic dysfunctions. The risk of renal, hepatic & CNS injury is more with parenteral route. Drugs like cimitidine or erythromycin are known to have harmful drug interaction with colchicin. It is
contraindicated,ln pregnancy & lactation.
Role of NSAIDS in acute attack:
Indomethacin 50 mg orally 4-6 hourly until attack subsides, then tapered off over 7 -10 days
Phenylbutazone 200 mg tds after food
Corticotrophin gel: 60-100 units in daily for 2-3 days may terminate severe attack
Indications for prophylactic therapy / interval therapy:
Presence of renal disease
Family history of renal or heart disease
Young patient with high uric acid levels (> = 9 mg/lr)
Diet in chronic gout:
It should be low in purines & fats
No sweet bread, kidney, liver, meat extracts, peas, beans & lentils
Prophylactic drug therapy:
3. Uricosuric agents
I. Colchicin: It is a safe and effective drugs which prevents acute attacks. Since it does not have uricosuric effect and does not affect tophceaus deposition, it should be combined with uricosuric drugs or allopurinol. The suggested doss is 0.5 mg/day or twice daily.
II. Allopurinol: It is an inhibitor of the enzyme anthine oxidase; there by preventing the final step in the production of uric acid. By reducing serum urate and maintaining it at that level, the size of urate deposits can be reduced and progression of renal lesion is halted.
Dosage and administration: It is started at 300 mg/day. In order to avoid exacerbation of acute gaut due to sudden and rapid changes in uric acid levels a lower dose of 100 mg/day is started which is
gradually increased by 100 mg/week till the desired levels are reached.
Patients with gout and
a. Evidence of urate overproduction (24 hour urinary uric acid> 800 mg)
c. Renal insufliciency (creatinine clearance < 80 ml/min)
d. Tophaceous deposits.
e. Age over 60 years or
f. Inability to take uricosuric agents because of inaffectiveness or intolerance. .
Patient with nephrolithiasis of any type plus urinary uric acid excertion greater than 600 mg / day
Patient with or at risk for acute uric acid nephropathy
Patient with renal calculi composed of 2,8 - dihydroxyadenine
Contraindication: Children, acute gout.
Should not be used along with iron therapy
To maintain adequate fluid intake
Renal or hepatic impairement
ADR: These include
Bone marrow supression Hepatitis
Stevens Johnson syndrome Urticaria
Acute renal failure Vasculitis
III. Uricosuric agents: These act by increasing renal excretion of uric acid and are effective in the treatment of uncomplicated cases of gout. Due to high risk of urolithiasis with these medication, these are contraindicated in renal diseases.
Dosage: Probenecid is effective at the dose of 1-2 gm/day Sulfinpyrazone is initially started as 50- 100 mg twice daily with a gradual increase to 200 mg twice daily.
Adequate fluid intake must be maintained.
Sodium bicarbonate 1 gm three times a day to maintain alkaline urine levels is recommended.
Probenecid prolongs the half-life of penicillin, heparin, salicylates and indomethacin.
Intermittent treatment or the cessation of drug therapy may lead to recurrence of acute attacks within 6 months and formation of tophi within 3 years. Urate-lowering drug therapy therefore Should be continue lifelong.
Medications with uricosuric Activity:
-Ascorbic acid -Phenylbutazone
-Calcitonin -Salicylates (>2g/d)
-Estrogen -Radiographic contrast agent
1. Immobilization and splintage for prevention of joint destruction.
2. Large tophi that interfere with joint and tendon motion may be removed.
Arthritis due to deposition of calcium crystals
CPPD Deposition Disease (calcium pyrophosphate dihydrate)
Pathogenesis: The deposition of CPDD crystals in articular cartilage, synovium & periarticular ligaments & tendons is most common in elderly more than 65 years of age.
Conditions associated with CPDD disease
Disease – associated:
Chronic tophacecus gaut
Epiphysical dysplasias ,
Hereditary: e.g. French, Swedish, English, Japanese etc.
The deposition is polyarticular in atleast 2-3rd of patients. The knee joint is the joint most frequently affected. Unlike osteoarthritis metacorpophalangeal, wrist, elbow, shoulder & ankle joint may also be involved. Rarely tempnomandibular joint & ligament flavum of the spinal canal are involved. In 50% of cases fever may be present making it difficult to differentiate from pygenic arthritis.
Acute attacks may be precipitated by trauma, surgery of joint or even a long walk. Rapid decline in serum calcium levels specially in severe medical illness or after surgery (especially parathyroidectomy) can lead to pseudogout.
Isolated pseudogout: An acute inflammatory episode involving a large joint such as knee with h/o remissions or exacerbation: Usually there are no significant systemic menifestations. Pseudorheumatoid arthritis: It resembles rheumatoid disease, involving knees. Wrists, elbows and metacarpophalangeal joints. It is the least common menifestation of pseudogout.
Pseudo- osteoarthritis: Bilateral symmetrical, acute, isolated inflammatory episodes of arthritis super imposed on osteoarthritic changes involving knees, wrists, shoulders, elbows and ankles may be seen.
Asymptomatic: Incidental findings in largely asymptomatic joint.
Severe generalized febrile disorder: It is associated with high fever, elevated WBC count, elevated ESR and polyarticular joint involvement.
X-rays: It may show punctate and/or linear radiolense deposits in fibrocartilaginous joint monisci or articular hyaline cartilage.
Definitive Diagnosis: It is based on demonstration of rod shaped or rhomboid crystals with weak positive birefringence in synovial fluid.
Induction or enhancement of peculiar form of osteoarthritis.
Induction of severe resorptive disease mimicking charcot's arthritis.
Production of symmetric proliferative synovitis, clinically similar to RA & frequently seen in familial forms with early onset.
Intervertebral disk & ligament calcification with restriction of spinal mobility, mimicking ankylosing spondylitis
Calcium HA deposition disease
HA which is the primary mineral of bone & teeth, sometimes get deposited in areas of tissue damage mimicking other crystal deposition disease.
Conditions associated with HA deposition disease:
Haemorragic shoulder effusions in the elderly (Millwaukees shoulder)
Renal failure I long-term dialysis
Connective tissue disease
Heterotropic calcification following stroke, spinal cord injury
- More common in elderly
- It may be associated with acute and/or chronic damage to the joint capsule, tendon, bursa, articular surface
with sometimes both periarticular and articular deposits coexisting
- Commonest joints involved are knees, shoulders, hips & fingers
- Clinically types: -Asymptomatic radiographic abnormalities
-Chronic destructive arthopathy
X-rays: It may/ may not show calcification with or without destruction
Synovial fluid: - Predominantly mononuclear, cell count is usually < 2000 cells / uL but not more
Than 50,000 cells/uL
- Individual crystals are very small, nonbifrigent & can only be seen by
Treatment: It is similar to CPPD disease
Caox deposition disease
Primary oxalosis is a rare heriditary metabolic disorder with poor prognosis. Secondary oxalate deposition may occur in end stage renal disease, those on long-term hemodialysis or peritoneal dialysis.
Clinical features: There are similar to other crystal deposition
Deposits have been documented in fingers, wrists, elbows, knees, ankles & feet.
Diagnosis: Diagnosis is based on demonstration of bipyramidal crystals having strong positive birefrigence on polarized microscope.
Treatment: It is similar to other deposition disease.