Metabolic conditions and the musculoskeletal system

Metabolic conditions and the musculoskeletal systemJohan van RensburgCRYSTAL-INDUCED ARTHRITIS

TYPESMonosodium urate monohydrateCalcium pyrophosphateCalcium hydroxyapatiteCholesterolURIC ACID POOLEndogenousExogenousSerum urate: 0,12 - 0,55mmol/lUrine urate excretion: 1,5 - 4,4mmol/24 hoursIntestines (1/3) ExcretionKidneys (2/3)MECHANISM OF HYPERURICAEMIAOverproductionUnderexcretionHYPERURICAEMIA AND GOUT(MONOSODIUM URATE)disorder of purine metabolismcharacterisedhyperuricaemiadeposition of uric acid or urate crystals in the tissues manifests as acute attacks of gouty arthritis tophikidney stonesurate-nephropathyPATHOGENESISHyperuricaemia causes gout, but is not synonomous with goutFactors promoting crystallisation (0.55mmol/l)the level of saturationsolubilitypH and temperature of the limbPATHOGENESISCrystallisation in jointCrystal absorbed by PMNSecretion lysozyme enzymesSevere synovitis

ACUTE GOUTY ARTHRITIS INCIDENCEMostly men > 40yrsSometimes postmenopausal women (Often on Diuretics)CLINIAL PICTURE ACUTE GOUTY ARTHRITISGoes to bed healthyWakes up sudden monoarthritis ( 85% Podagra)(heel, instep, knee, wrist and hands and elbow -olecranon bursitis)Rigors with severe painNight spent in tortureJoint is red (ripe tomato),warm and very tender.After attack skin around the joint often peels offAcute attacks usually pass completely until the next attackUncontrolled hyperuricaemia may lead to polyarticular goutACUTE GOUTY ARTHRITIS

PERCIPITATING CAUSES ACUTE GOUTY ARTHRITIS Trauma and surgeryMedicationAlcoholDietACUTE GOUTY ARTHRITIS

DIAGNOSIS OF GOUTFamily history, as well as a typical history of attacksTypical clinical picture and tophiElevated serum urate - (may be normal during attacks)Urate crystals in aspiration fluid (as well as tophi)X rays: Punched-out erosions (Rat bitten)

TREATMENTExclude precipitating causesA low purine diet and avoidance of alcohol are recommendedFoods with a very high purine content: anchovy, sardines, liver and kidneys. Most meats, fish and chicken products also have a high purine content.Treatment of acute attacksLong-term preventive treatmentTreatment of associated conditions such asobesityhypertensionhyperlipaemiakidney failureRX ACUTE ATTACKAvoid initiation of prophylactics with an acute attackProphylactic therapy is not discontinued if a patient is already on therapyNSAIDS ( not used in kidney failure)Colchicine Corticosteroids (in resistant cases)Prevention ?

Progression in the diseaseAsymptomatic hyperuricaemiacontinues until possible first attackAcute gouty arthritisInterval hyperuricaemia periods between attacksChronic tophaceous goutComplicationskidney stones and nephropathy CHRONIC TOPHACEOUS GOUTDeposition of uric acid crystals in the tissues (tophi)After repeated attacks after 11 - 12 yearsThe tophi occur in The auricles - helixTendons (hands, achilles tendon and feet) Bursae - especially olecranon bursaThe tophi may ulcerate with secretion of pasty materialTOPHI

GOUTY TOPHUSINDICATIONS FOR LONG-TERM PROPHYLACTIC THERAPY If conservative measures do not have the desired effect and the levels still remain high (> 0.55 - 0.6 mmol/l) with repeated attacks (If less than 1 attack per year is experienced, treatment is not necessary) Positive family history of gout and kidney stones with very high urate levels Chronic tophaceous gout Kidney stones or nephropathyMEDICINES FOR LONG-TERM PROPHYLAXISAllopurinol 300mg/dayUricosurics medicinesProbenecid 250mg bdMust not be used if there is kidney failure or kidney stonesTo avoid kidney stones a high fluid intake (2l/day) must be maintained and in addition the urine can be alkalised with something like citrosodaColchicine 0.5mg should be added once or twice daily for the first few months in order to prevent recurrent attacksCPPDDEFINITIONArthropathy and other locomotor disease associated with CPPD crystal depositionSporadic, familial, and metabolic disease-associated forms recognizedCLINICAL FEATURESPredominantly a disease of the elderlyAcute self-limiting synovitis (pseudogout)Chronic arthropathy showing strong association/overlap with OATarget joints knees, wrists (shoulders, hips)EPIDEMIOLOGYFemale preponderanceRare under age 50, 1015% in those aged 65753060% in those over 85 years Framingham study showed an overall prevalence rate of 827% in those >85 yearsMETABOLIC ASSOCIATIONS Many reflect chance concurrence of common age-related conditions DiabetesUremiaPagets diseaseHypothyroidismOchronosisGoutSTRONGEST EVIDENCEHyperparathyroidismHemochromatosis HypophosphatasiaHypomagnesemiaWilsons diseaseCOMMON PRESENTATIONSAcute synovitisChronic arthritisIncidental finding DISTRIBUTIONAny joint may be involvedKnee commonest site Followed bywristshoulderankle elbow

INVESTIGATIONSFluid and tissue analysis Plain radiographsOther investigations may be undertaken to exclude alternative or coexisting arthropathyCPPD Crystal IdentificationAspirated fluid turbid / blood-stainedGreatly elevated cell count (usually >90% neutrophils). CPPD crystals poorly visualized LMPolarized light microscopy Morphology (usually rhomboids or rods)Weak positive birefringenceMay often be missed

RADIOGRAPHICCalcificationStructural changesCALCIFICATIONFibrocartilage knee menisciwrist triangular cartilagesymphysis pubisAlso in hyaline cartilage Capsular and synovial calcification is less common metacarpophalangeal joints and knee

ACHILLIS CALCIFICATION

PATELLOFEMORAL

Additional InvestigationsAspirated fluidGram stain and culture Moderate acute phase responseElevationplasma viscosityESRacute phase reactants (e.g. C reactive protein)peripheral white cell count (neutrophils)SCREENINGPredisposing Metabolic DiseaseUnrewardingWarranted in the following circumstancesearly onset arthritis (