Crystal associated diseases

Crystal associated disease Variety of crystals can deposit in and around joints and associated with both acute inflammatory and chronic syndromes

Crystal associated disease Crystals Common Mono sodium urate Mono hydrate Calcium pyrophosphate Dihydrate Uncommon Cholesterol Calcium oxalate Extrinsic crystals As plant thorn association Acute gout Chronic tophaceous gout Acute pseudo gout Chronic pyrophosphate arthropathy Chrondrocalcinosis Chronic effusion in RA Acute arthritis in dialysis patient Acute synovitis Chronic monoarthritis

Crystal associated disease Gout : is the pathological reaction of the joint or periarticular tissues to the presence of the monosodium urate mono hydrate (MSUM) crystal Clinically may present as inflammatory arthritis, bursitis, tenosynovitis, cellulitis, or nodular ( tophaceous ) crystal deposit

Epidemiology Male predominance 10 :1 Prevalence Increase with age and high uric acid concentration Primary : without cause Secondary due to renal impairment or drug therapy mainly affect ages over 65 yrs and usually seen in women

factors affecting uric acid level Gender Age Body bulk Genetic

Etiology and pathogenesis One third of the body uric acid derived from dietary source 2/3 excreted by the kidney, 1/3 via the gut 75 % of primary gout result from defect in uric acid excretion 20 % are over producers of uric acid

Etiology and pathogenesis 1% have specific inherited enzyme defect of purine synthesis, they should be suspected : 1.If gout developed at early age <25 2.If urolithiasis is the presenting feature 3.If there is strong family history of early onset gout

Risk factors for gout Obesity High alcohol intake Type IV hyperlipoproteinaemia, hypertension and IHD Unidentified inherited alteration in tissue factors related to inhibition / promotion of crystal formation

Factors that predispose to chronic hyperurecimia an gout Diminished renal excretion (more common ) Inherited isolated renal tubular defect Renal failure chronic drug therapy : thiazide and loop diuretic, low dose aspirin, cyclosporin, pyrazinamide Lead toxicity Lactic acidosis ( alcohol )

Factors that predispose to chronic hyperurecimia an gout Increase production of uric acid Increase purine turn over as chronic myeloproliferative or lymphoproliferative disorder Increased de novo synthesis ( over producers ) 1. Unidentified abnormality (most common ) 2. Specific enzyme defect A. Hypoxanthine – guanine phosphoribosyl transferase deficiency (HGPRT ) B. Phosphoribosyl pyrophosohate synthetase overactivity C. Glucose -6- phosphatase deficiency

Clinical features Acute gout The first MTP joint is affected in over 50 % Other common sites are the ankle, midfoot, knee, small joints of the hand, wrist and elbow Rapid onset, reach max severity in 2 -6 hrs often at early morning Extreme tenderness

Clinical features Marked swelling with redness and shiny skin Self limiting over days Fever, malaise and confusion Acute attack may presented as bursitis, tenosynovitis or cellulitis Polyarticular attacks are rare

Clinical features Intercritical period : These are asymptomatic period between attacks Mostly second attack occurs within 1 year The frequency of attacks and number of sites involved gradually increase with time Continued MSUM deposition causes joint damage and chronic pain The interval between the first attack and the development of chronic symptoms averages around 10 years

Chronic tophaceous gout Large MSUM deposits produces irregular firm nodules (tophi ) around extensor surface of finger, hand, forearm, elbow, Achilles tendon and sometime helix of the ear Large nodule may ulcerate discharging white gritty material associating with local inflammation ( erythema ) Marked asymmetry locally and between side

urolithiasis Uric acid stones cause renal colic in around 10 % of gout patients in Europe Favoring factors Purine over production Uricosuric drugs and defect in tubular absorption of uric acid Dehydration and lowering of urine pH ( e.g. chronic diarrhea and ileostomy

Chronic urate nephropathy Progressive renal disease is an important complication confined to untreated severe chronic tophaceous gout Result from MSUM deposition in the interstitium of the medulla and pyramids leading to chronic inflammation, giant cell reaction, fibrosis, glomereolosclerosis and secondary pyelonephritis

investigations Increase CRP and neutrophil ESR is raised in tophaceous gout S.uric acid elevated and may be normal during attack Measurement of 24 hr. urinary uric acid excretion J. aspiration and identification of MSUM crystal, the fluid is turbid due to elevated cell count (>90 % neutrophil ) B urea, S.creatinine

Radiograph In early stages usually normal Narrowing of joint space, sclerosis, cyst and osteophyte ( changes of OA ) occurs with time or predispose to secondary gout Gouty erosion ( bony tophi ) are less common but more specific ( punch out defect with retained bone density ) Tophi may be visible as eccentric soft tissue swelling

Management Acute attack NSAIDs as naproxin, diclofenac, indomithacin Oral colchicin ( potent inhibitor of neutrophil microtubular assembly ) loading dose 1 mg then 0.5 mg 6 hourly until symptoms abate Side effects : vomiting and diarrhea Intra articular steroids

Management Long term management Decrease weight in obese patient Decrease alcohol intake Stop drugs causing hyperuricaemia Decrease high purine diet

Management Prolonged hypouricaemic drug treatment is indicated for : Recurrent attacks of acute gout Tophi Evidence of bone or joint damage Associated renal disease Gout with greatly elevated serum uric acid

Management Allupurinol is the drug of choice, it inhibit xanthine oxidase and reduce conversion of hypoxanthine and xanthine to uric acid mg / day, lower dose used in old patient and if renal function is impaired Should be used with colchicine to prevent precipitation of acute attack

Management The serum uric acid should be measured every 6 weeks until level is decrease, to ensure dissolution of crystal and to prevent new crystal formation In most cases allupurinol will need to be continued indefinitely Uricosuric drugs as probenecid (0.5 1 g 12 hourly ), or sulfinpyrazone ( 100 mg 8 hourly )

Management Those drugs are contraindicated : In over producers In patient with renal impairment In patient with urolithiasis The uricosuric benzbromarone (100 mg / day ) is effective in patients with mild to moderate renal failure

Asymptomatic hyperuricaemia Treatment is unnecessary unless there is a strong family history of gout, urolithiasis or persistently very high levels (> 0.6 mmol / l )

Calcium pyrophosphate dihydrate (CPPD )crystal deposition Is a common age associated phenomenon (<55) that particularly targets the knee Often clinically occult, but can cause acute self –limiting synovitis ( pseudogout ) Occur as chronic arthritis showing strong association / overlap with OA

epidemiology Rare under age of % in those aged – 60 % in those over 85 The knee is the most prevalent site followed by the wrist and the pelvis More common in women

etiology Aging (sporadic ) OA ( common ) Familial predisposition (rare ) Metabolic cause (rare ) ( hemochromatosis, hyperparathyroidism, hypophospatasia, hypomagnesaemia, Wilsons’ disease)

Clinical features Acute synovitis (pseudogout ): Most common cause of acute monoarthritis in the elderly Triggering factors include direct trauma, intercurrent illness or surgery Resembles acute gout Develop rapidly with severe pain, stiffness and swelling, maximum within 6-24 hrs. of onset Fever may appear Self limiting, but may take 1-3 weeks

Differential diagnosis Sepsis Gout

Chronic ( pyrophosphate ) arthritis The knees being the worst affected, then wrist, shoulders, elbows, hip and midtarsals Acute attacks may be superimposed on this chronic history Chronic pain, variable early morning and inactivity stiffness and functional impairment Affect single or multiple joints Affected joints show features of OA DDx : RA

Investigations Examination of the synovial fluid using compensated polarized microscopy will demonstrate CPPD crystals (showing weak Birefringence (positive sign ) and predominantly rhomboid morphology ) The synovial fluid is often turbid and may be uniformly blood- stained

Investigations Gram stain and culture was –ve Radiographs shows punctate and linear densities in hyaline articular cartilage or fibrocartilaginous tissues, with or without associated structural changes of OA

Investigations Screening of metabolic or familial predisposition should be done in : Early onset <55 yrs. Old Florid polyarticular Recurrent acute attacks without chronic arthropathy

Management Joint aspiration and intra articular steroid is usually required Oral NSAID, colchicin For chronic arthropathy, is the same as for OA