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Clinical manifestations and diagnosis of gout

Author Michael A Becker, MD Section Editor H Ralph Schumacher, MD Deputy Editor Paul L Romain, MD

Last literature review version 19.1:

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$% &'D(C $'% ( )out *mono+odium urate cr!+tal depo+ition di+ea+e, i+ characteri-ed &iochemicall! &! e.tracellular fluid urate +aturation. /he clinical manife+tation+ include one or more of the followin01 Recurrent attack+ of acute inflammator! arthriti+ 2hronic arthropath! Accumulation of urate cr!+tal+ in the form of tophaceou+ depo+it+ 3ric acid nephrolithia+i+ A chronic nephropath! that in 0out! patient+ i+ mo+t often due to comor&id +tate+ All patient+ with 0out ha4e h!peruricemia *+aturation of +erum for urate, at +ome point in their di+ea+e. *See 53ric acid &alance5., Howe4er, mo+t h!peruricemic indi4idual+ ne4er e.perience a clinical e4ent re+ultin0 from urate cr!+tal depo+ition. /hu+, the dia0no+i+ of 0out focu+e+ on the fundamental pathoph!+iolo0ic e4ent+ definin0 the clinical +tate1 ti++ue depo+ition of urate cr!+tal+ and the accompan!in0 inflammator! and potentiall! de+tructi4e con+e6uence+. 7ithin thi+ framework, h!peruricemia i+ 4iewed a+ a nece++ar! &ut not +ufficient precondition for the de4elopment of urate cr!+tal depo+ition di+ea+e and i+ to &e di+tin0ui+hed from 0out, the clinical +!ndrome. /he clinical manife+tation+ and dia0no+i+ of 0out will &e re4iewed here. 8++ue+ related to a+!mptomatic h!peruricemia, the treatment of acute 0out, and pre4ention of recurrent 0out are di+cu++ed +eparatel!. *See 5A+!mptomatic h!peruricemia5 and 5/reatment of acute 0out5 and 5Pre4ention of recurrent 0out5., )$S '&$CAL *E&S*EC $+E( De+cription+ of the epidemiolo0!, clinical feature+, and natural hi+tor! of 0out e4ol4ed o4er more than two millennia of +tud!. /he la+t half of the twentieth centur! produced confirmation that the patho0ene+i+ of 0out in4ol4e+ urate cr!+tal depo+ition. Pi4otal in thi+ pro0re++ wa+ the introduction of polari-ed li0ht micro+cop! into clinical practice, pro4idin0 urate cr!+tal identification in +!no4ial fluid a+ the mean+ to achie4e rapid and definiti4e dia0no+i+ and to re+ol4e the formerl! am&i0uou+ relation+hip &etween h!peruricemia and 0out 9 $:. Studie+ o4er the pa+t few decade+ ha4e increa+ed under+tandin0 of the molecular pathoph!+iolo0! of 0out! inflammation. *See 5Pathoph!+iolo0! of 0out! arthriti+5., %inall!, the de4elopment of dru0+ capa&le of +uppre++in0 0out! inflammation and h!peruricemia ha+ pro4ided the clinician with the mean+ to pre4ent, and e4en re4er+e, the pre4iou+l! ra4a0in0 affect+ of acute inflammator! and chronic de+tructi4e manife+tation+ of urate cr!+tal depo+ition. Althou0h the+e ad4ance+ ha4e fa4ora&l! influenced the cour+e of 0out in the ma;orit! of affected indi4idual+, the di+order per+i+t+ a+ a pro&lem 9":, often with le++ than optimal clinical outcome+ de+pite attempt+ at treatment 9':. /hi+ i+ particularl! true amon0 noncompliant or poorl! in+tructed patient+ 9 <,=:, and patient+ who do not fit what ma! ha4e &een con+idered 5cla++ic5 clinical profile of the 0out! patient *that i+, a '# to ># !ear old man who i+ likel! to &e o&e+e, h!perten+i4e, and a fre6uent im&i&er of alcohol,. /he+e other at?ri+k 0roup+ differ from the cla++ic profile in term+ of a0e, in4ol4ement of women 9 >?@:, and concurrent illne++e+ and therapie+ *e0, diuretic+ and c!clo+porine, 9 @?$#:. *See 5Diuretic?induced h!peruricemia and 0out5 and 5H!peruricemia and 0out in renal tran+plant recipient+5 ., A+timate+ of the pre4alence of 0out in the 3nited State+ ran0e from le++ than ' million 9 $$: to = million indi4idual+ 9$":B &oth the incidence 9$',$<: and pre4alence 9 $=,$>: of the di+ea+e appear to &e increa+in0 in the 3nited State+ and worldwide. CLASS$,$CA $'% ( Per+i+tent h!peruricemia i+ a common &iochemical a&normalit! that re+ult+ from e.ce++i4e urate production andCor dimini+hed renal uric acid e.cretion. *See 53ric acid &alance5., Per+i+tent h!peruricemia can &e di4ided into two cate0orie+1 Primar! h!peruricemia, which u+uall! la+t+ indefinitel!, de+cri&e+ urate +aturation ari+in0 in the a&+ence of coe.i+tin0 di+ea+e+ or dru0+ that alter uric acid production or e.cretion. Secondar! h!peruricemia refer+ to e.ce++i4e urate production *ta&le $, or dimini+hed renal clearance *ta&le ", that i+ the re+ult of another di+ea+e, dru0, dietar! product, or to.in. CL$%$CAL S-%D&'"ES ( /he three cla++ic +ta0e+ in the natural hi+tor! of pro0re++i4e urate cr!+tal depo+ition di+ea+e *0out, are1 Acute 0out! arthriti+ 8ntercritical *or inter4al, 0out 2hronic recurrent and tophaceou+ 0out

8t ma! &e worthwhile to re0ard the +ta0e+ of 0out a+ emer0in0 +e6uentiall!, with clinical +e4erit! often parallelin0 the fre6uenc! of acute 0out flare+ and, ultimatel!, the de4elopment of chronic 0out! arthropath! and tophaceou+ 0out. 8n thi+ conte.t, current treatment with antih!peruricemic *urate?lowerin0, a0ent+ i+ not curati4e &ut ma! re+et the cour+e of the indi4idual patient and pro4ide what i+ e++entiall! a cure if therap! i+ maintained. 7ith current effecti4e therapie+, pro0re++ion of 0out to the chronic tophaceou+ +ta0e i+ now le++ fre6uent amon0 the ma;orit! of compliant patient+ with primar! 0out, and mo+t patient+ with +econdar! 0out 9 $D:. 7hen pro0re++ion doe+ occur, it i+ mo+t often amon0 noncompliant patient+, tho+e in whom the mana0ement +cheme ha+ not &een appropriatel! communicated, and tho+e in whom the dia0no+i+ of 0out ha+ not &een made. Other patient+ lia&le to +how pro0re++ion of 0out include tho+e intolerant of or treated with inade6uate do+e+ of urate?lowerin0 a0ent+, tho+e recei4in0 medication+ *u+uall! for comor&iditie+, that interfere with urate?lowerin0 a0ent+, and or0an tran+plant recipient+. /he+e con+ideration+ differ from tho+e a++ociated with the manife+tation+ of acute h!peruricemia *primaril! acute renal failure, +een in the tumor?l!+i+ +!ndrome or with other cau+e+ of ma++i4e ti++ue &reakdown. *See 53ric acid renal di+ea+e+5, +ection on EAcute uric acid nephropath!E., AC( E .'( - A& )&$ $S ( Acute 0out! arthriti+ u+uall! occur+ after !ear+ of a+!mptomatic h!peruricemia. *See 5A+!mptomatic h!peruricemia5., ypical attac/ ( /he t!pical attack of acute 0out! arthriti+, which i+ inten+el! inflammator!, include+ the followin0 clinical feature+1 Se4ere pain, redne++, +wellin0, and di+a&ilit!. Ma.imal +e4erit! of the attack i+ u+uall! reached within $" to "< hour+. 2omplete re+olution of the earlie+t attack+ almo+t alwa!+ occur+ within a few da!+ to +e4eral week+, e4en in untreated indi4idual+. Lower e.tremit! in4ol4ement. At lea+t @# percent of initial attack+ in4ol4e a +in0le ;oint, mo+t often at the &a+e of the 0reat toe *fir+t metatar+ophalan0eal ;oint, known a+ poda0ra,, or the knee. Si0n+ of inflammation e.tendin0 &e!ond the confine+ of the ;oint that i+ primaril! in4ol4edB thi+ feature ma! 0i4e the impre++ion of arthriti+ in +e4eral conti0uou+ ;oint+, or of teno+!no4iti+, dact!liti+ *+au+a0e di0it,, or e4en celluliti+. 8n4ol4ement in an ankle or in+tep, or in a wri+t, fin0er, or olecranon &ur+a can occur initiall!, &ut i+ more common in a recurrent epi+ode of 0out! arthriti+. Other potential +ite+ of in4ol4ement include other &ur+a+, +houlder+, hip+, +ternocla4icular ;oint+, +pine, and +acroiliac ;oint+, which ma! cau+e dia0no+tic confu+ion. More +u&tle inflammator! epi+ode+ appear to occur in +ome patient+, &ut the+e ha4e not &een well +tudied. 8n +ome ca+e+ *e0, trauma, +ur0er!, or in the earl! month+ of urate?lowerin0 dru0 therap!,, 0out occur+ with normal or e4en low +erum urate concentration+ at the time of the acute e4ent. O4erall, normal to low +erum urate 4alue+ ha4e &een noted in from $" to <' percent of patient+ with acute epi+ode+ of 0out 9 $@?"$:. /he initiation of urate?lowerin0 therap!, althou0h protecti4e in the lon0 term, can precipitate acute 0out! arthriti+. A+ a re+ult, proph!la.i+ i+ u+uall! 0i4en to pre4ent thi+ complication. *See 5Pre4ention of recurrent 0out5, +ection on EProph!la.i+ durin0 initiation of antih!peruricemic therap!E ., *redisposing factors ( Fumerou+ circum+tance+ promote or are a++ociated with acute attack+ of 0out! arthriti+1 /rauma, +ur0er!, +tar4ation, fatt! food+ and other dietar! o4erindul0ence, deh!dration, and in0e+tion of dru0+ affectin0 *rai+in0 or lowerin0, +erum urate concentration+ *e0, allopurinol, urico+uric a0ent+, thia-ide or loop diuretic+,, and low?do+e a+pirin ma! all promote 0out! attack+. 8n men, increa+in0 alcohol con+umption *&eer and +pirit+, &ut not wine, i+ a++ociated with a proportionatel! 0reater ri+k of de4elopin0 0out 9"":. Aach of the+e circum+tance+ ma! pro4oke 0enerali-ed di+tur&ance+ in e.tracellular fluid urate concentration+ or ma! affect cr!+tal+ in the inflammator! milieu 9"':. Hi0h le4el+ of meat and +eafood con+umption are a++ociated with hi0her +erum urate concentration+, while increa+ed intake of low?fat dair! product+ correlate+ with lower urate le4el+ 9 "<:. /he amount+ of meat and +eafood in the diet are +i0nificantl! a++ociated with an increa+ed ri+k of de4elopin0 0out! arthriti+. /hi+ wa+ illu+trated in a pro+pecti4e +tud! of <D,$=# male health profe++ional+ 9"=:. /ho+e in the hi0he+t 6uintile of meat con+umption had an ad;u+ted ha-ard ratio *HR, of $.<$ compared with the lowe+t 6uintileB tho+e con+umin0 the lar0e+t amount of fi+h had a HR of $.=$. Feither the intake of purine?rich 4e0eta&le+ nor total protein intake wa+ a++ociated with an increa+ed ri+k of 0out. On the other hand, the hi0he+t 6uintile of dair! product con+umption wa+ a++ociated with a +i0nificant reduction in ri+k *HR of #.=>, 9 "=:. 8n a +eparate report, hi0her coffee con+umption wa+ al+o a++ociated with a lower ri+k of acute 0out 9">:. 2offee, &ut not tea con+umption, reduced the ri+k of ha4in0 h!peruricemia, +u00e+tin0 that the uric acid lowerin0 effect i+ not due to caffeine, &ut other, a+ !et unidentified, component+ of coffee 9 "D:. Locall! ele4ated urate concentration+ 9"@:, in con;unction with repeated ;oint microtrauma, prior de0enerati4e chan0e, or reduced temperature in poorl! perfu+ed di+tal ti++ue+ 9"G:, ma! predi+po+e indi4idual ;oint+ to 0out! inflammation. Low?0rade inflammation in multiple o+teoarthritic interphalan0eal ;oint+ *He&erdenE+ and BouchardE+ node+, ma!

Low?0rade inflammation in multiple o+teoarthritic interphalan0eal ;oint+ *He&erdenE+ and BouchardE+ node+, ma! herald the on+et of coe.i+tin0 0out! arthriti+ 9'#,'$:, particularl! in elderl! indi4idual+ with chronic kidne! di+ea+e or tho+e recei4in0 diuretic therap!. *See 5Diuretic?induced h!peruricemia and 0out5., Acute polyarticular gout ( Pol!articular 0out! arthriti+ i+ the initial manife+tation in le++ than "# percent of patient+ with 0out, &ut occur+ with increa+in0 fre6uenc! in later flare+. Pol!articular +!mptom+ are particularl! common late in the cour+e of untreated 0out, when multiple recurrence+, +hort or a&+ent +!mptom?free inter4al+, and palpa&le tophaceou+ depo+it+ are common. *See 5A4aluation of the adult with pol!articular pain5., A pol!articular initial pre+entation of 0out! arthriti+ ma! &e more fre6uent in patient+ in whom h!peruricemia and 0out ari+e +econdar! to a m!eloproliferati4e or l!mphoproliferati4e di+order or in or0an tran+plant recipient+ who are recei4in0 c!clo+porine A. *See 5H!peruricemia and 0out in renal tran+plant recipient+5 ., Diagnosis of acute gout ( A definiti4e dia0no+i+ +hould &e +ou0ht when acute 0out i+ +u+pected, &oth to e.clude alternati4e e.planation+ for the acute e4ent and to en+ure that lon0?term, e.pen+i4e, and potentiall! to.ic urate?lowerin0 medication+ are not pre+cri&ed unnece++aril! if there i+ recurrence or pro0re++ion of the arthriti+. /he dia0no+i+ of acute 0out i+ mo+t +ecure when +upported &! 4i+uali-ation of urate cr!+tal+ &! e.perienced e.aminer+ in a +ample of fluid a+pirated from an affected ;oint *or &ur+a,. 8f cr!+tal confirmation of the dia0no+i+ cannot &e made, a pro4i+ional dia0no+i+ ma! &e made on the &a+i+ of clinical data, includin0 hi+tor!, ph!+ical e.amination, appropriate la&orator! te+t+ and, increa+in0l!, ima0in0 +tudie+. *olari0ing microscopy ( S!no4ial fluid o&tained from ;oint+ or &ur+a+ *a+ well a+ material a+pirated from tophaceou+ depo+it+, if an!, ma! &e directl! e.amined u+in0 compen+ated polari-ed li0ht micro+cop!. Durin0 an acute 0out! epi+ode, a+piration of the affected ;oint and polari-ed compen+ated li0ht micro+cop! of +!no4ial fluid permit detection of intracellular mono+odium urate cr!+tal+ in +!no4ial fluid. /he +en+iti4it! of thi+ techni6ue in demon+tratin0 ne0ati4el! &irefrin0ent cr!+tal+ within neutrophil+ in patient+ with acute 0out! arthriti+ i+ at lea+t @= percent, and the +pecificit! for 0out i+ $## percent 9'",'':. Howe4er, acute 0out! arthriti+ ma! occa+ionall! coe.i+t with another t!pe of ;oint di+ea+e, +uch a+ +eptic arthriti+ or p+eudo0out. /he +en+iti4it! of the ;oint fluid anal!+i+ can &e impro4ed &! e.amination of the +ediment in a centrifu0ed +pecimen 9 '<:. Additional approache+ to con+ider in the e4ent of a ne0ati4e *no urate cr!+tal+ +een, +tud! durin0 the acute attack include a+piration of a concurrentl! inflamed ;oint or *le++ helpful in rulin0 out an accompan!in0 cau+e for the acute e4ent, a+piration of an uninflamed &ut pre4iou+l! in4ol4ed ;oint or of a tophu+, if either i+ pre+ent. Criteria for clinical diagnosis of gout ( 8n the a&+ence of the mean+ to identif! urate cr!+tal+ or in the pre+ence of a ne0ati4e polari-ed li0ht micro+copic +tud!, a dia0no+i+ of 0out ma! &e made &! a com&ination of clinical and hi+torical criteria 9 '",'<?'>:. /hi+ method of dia0no+i+ mu+t &e re0arded a+ pro4i+ional and much le++ +pecific 9'=:. Pre4iou+l! propo+ed clinical, radio0raphic, and la&orator! criteria that ma! +till &e u+eful include1 A cla++ic hi+tor! of one or more epi+ode+ of monoarticular arthriti+ followed &! intercritical period*+, completel! free of +!mptom+ Ma.imum inflammation *with the feature+ de+cri&ed a&o4e, within "< hour+ 3nilateral fir+t metatar+ophalan0eal ;oint attack *poda0ra, Pre+ence of a 4i+i&le or palpa&le le+ion, which &! location or appearance i+ likel! to &e a tophu+ H!peruricemia Su&cortical &one c!+t+ apparent on plain radio0raph, ultra+ound e.amination di+pla!in0 t!pical feature+ of +!no4ial tophaceou+ depo+it+, or ma0netic re+onance ima0in0 *MR8, e.amination identif!in0 0out! ero+ion+. 2han0e+ of the+e t!pe+ +een in ima0in0 procedure+ are not u+uall! detecta&le at the time of the fir+t acute attack of 0out! arthriti+. /he accurac! of clinical dia0no+i+ without cr!+tal confirmation i+ uncertain. A +tud! on '# patient+ with cr!+tal pro4en 0out +howed that the pre+ence of " of ' of the Rome criteria *+erum uric acid 0reater than D m0CdlB pre+ence of tophiB or painful ;oint +wellin0 of a&rupt on+et and clearin0 within one to two week+, had a DD percent po+iti4e predicti4e 4alue. Fo clinical criteria were more than D# percent +en+iti4e or @G percent +pecific 9>#:. An appropriate clinical picture and an ele4ated +erum urate concentration +u00e+t the dia0no+i+ of acute 0out! arthriti+. Howe4er, a+ noted a&o4e, an apprecia&le num&er of flare+ occur in patient+ who at the time of the attack ha4e normal or e4en low +erum urate concentration+ *+ee E/!pical attackE a&o4e,. 2on4er+el!, patient+ with acute arthriti+ due to cau+e+ other than 0out ma! ha4e coincidental h!peruricemia. A dia0no+tic rule ha+ &een de4eloped to impro4e the accurac! of dia0no+e+ made without ;oint fluid anal!+i+, which incorporate+ man! of the feature+ de+cri&ed a&o4e. /he rule wa+ &a+ed upon an anal!+i+ of '"@ patient+ with monoarthriti+ +een initiall! &! famil! practitioner+ in the Fetherland+B the patient+ al+o underwent prompt e.pert +!no4ial fluid anal!+i+ 9'>:. /he model u+ed +e4en 4aria&le+ a++i0ned wei0hted +core+ that could &e readil! a+certained in primar! care to di+tin0ui+h three le4el+ of ri+k for 0out. /he followin0 4aria&le+ and +corin0 4alue+ were u+ed1 Male +e. *" point+, Pre4iou+ patient?reported arthriti+ attack *" point+,

Pre4iou+ patient?reported arthriti+ attack *" point+, On+et within one da! *#.= point+, oint redne++ *$ point, %ir+t metatar+al phalan0eal ;oint in4ol4ement *".= point+, H!perten+ion or at lea+t one cardio4a+cular di+ea+e *$.= point+, Serum uric acid le4el 0reater than =.@@ m0CdL *'.= point+, 8n the +tud! cohort, +corin0 for low *H< point+,, intermediate *I< to J@ point+, and hi0h *K@ point+, pro&a&ilit! of 0out identified 0roup+ with a pre4alence of 0out of ".", '$.", and @".= percent, re+pecti4el!. /hi+ approach !ielded +u&+tantiall! fewer fal+e po+iti4e dia0no+e+ than tho+e made clinicall! &! the famil! practitioner+ *$D 4er+u+ '> percent,. Patient+ fallin0 into the intermediate cate0or! would mo+t &enefit from further e4aluation with +!no4ial fluid anal!+i+. /hi+ rule wa+ applied onl! to patient+ with monoarthriti+ and re6uire+ e.ternal 4alidation in another primar! care +ettin0. %or ea+e of u+e, the author+ of the +tud! ha4e pro4ided an online calculator that pro4ide+ an a&+olute calculated ri+k at www.umcn.nlCRe+earchCDepartment+Ceer+teli;n+0enee+kundeCPa0e+C ichtcalculator.a+p. *acce++ed Fo4em&er "G, "#$#,. &esolution ( Re+olution of the acute 0out! attack i+ +ometime+ accompanied &! de+6uamation of the +kin o4erl!in0 the affected ;oint. /he ph!+iolo0ic &a+i+ of the re+olution of acute 0out! inflammation i+ comple., &ut center+ on attenuation of a num&er of patho0enetic factor+ 9 'D: *+ee 5Pathoph!+iolo0! of 0out! arthriti+5,. Differential diagnosis of acute gouty arthritis ( Se4eral other condition+ ma! mimic acute 0out! arthriti+. A+piration of +!no4ial fluid from the affected ;oint and anal!+i+ of the fluid &! )ram +tain, culture, and re0ular and polari-ed li0ht micro+cop! permit+ di+tinction of 0out from the di+order+ &elow in the 0reat ma;orit! of ca+e+ 9'','@:. *See EDia0no+i+ of acute 0outE a&o4e., /he differential dia0no+i+ of acute monoarticular 0out! arthriti+ include+ the followin01 Septic arthriti+ ( Acute monoarticular 0out can 0i4e a clinical picture indi+tin0ui+ha&le from acute +eptic arthriti+, includin0 fe4er, leukoc!to+i+, and ele4ated er!throc!te +edimentation rate. On rare occa+ion+, acute 0out and +eptic arthriti+ coe.i+t. *See 5Septic arthriti+ in adult+5 ., /rauma ( )out! attack+ of le++er +e4erit! ma! &e mimicked &! a +tre++ fracture or traumatic proce++ in the &one or ;oint. P+eudo0out ( %eature+ that help to differentiate &etween 0out and p+eudo0out are illu+trated in the ta&le * ta&le ',. 8n +ome ca+e+, &oth urate and 2PPD cr!+tal+ are identified in the +!no4ial fluid neutrophil+ in patient+ in whom the+e di+order+ coe.i+t. *See 52linical manife+tation+ and dia0no+i+ of calcium p!ropho+phate cr!+tal depo+ition di+ea+e5., Other cr!+talline arthritide+ ( Arthriti+ or periarthriti+ due to the depo+ition of &a+ic calcium pho+phate cr!+tal+ cannot u+uall! &e dia0no+ed with certaint! &! polari-ed micro+cop! &ecau+e the cr!+talline a00re0ate+ are &elow the re+olution of +tandard li0ht micro+cop! 9'G:. 8n thi+ +ettin0, tran+mi++ion electron micro+cop! and .?ra! powder diffraction ha4e &een +ucce++full! u+ed in the identification of the+e cr!+tal+. *See 52linical manife+tation+ and dia0no+i+ of calcium p!ropho+phate cr!+tal depo+ition di+ea+e5., Other ( /he differential dia0no+i+ amon0 patient+ with a hi+tor! of recurrent attack+ with +pontaneou+ re+olution or rapid and complete impro4ement with u+e of non+teroidal antiinflammator! dru0+, the differential dia0no+i+ include+ reacti4e arthriti+, palindromic rheumati+m, and acute rheumatic fe4er, in addition to p+eudo0out. *See 52linical feature+ of rheumatoid arthriti+5, +ection on EPalindromic rheumati+mE and 52linical manife+tation+ and dia0no+i+ of acute rheumatic fe4er5., 7hile man! ph!+ician+ are +killed at ;oint a+piration, tho+e who are not ma! re6ue+t the a++i+tance of an orthopedic +ur0eon or a rheumatolo0i+t to perform a ;oint tap and help with the anal!+i+ of the +!no4ial fluid. *See 5 oint a+piration or in;ection in adult+1 /echni6ue and indication+5 and 5S!no4ial fluid anal!+i+ and the dia0no+i+ of +eptic arthriti+5., $% E&C&$ $CAL .'( A%D &EC(&&E% .'( - A& )&$ $S ( 3pon re+olution of an acute attack of 0out, the patient i+ +aid to ha4e entered an intercritical *&etween attack+, period. A4en after +e4ere and incapacitatin0 acute attack+, intercritical period+ earl! in the cour+e of 0out are mo+t often entirel! a+!mptomatic. /hi+ +e6uence i+ +o uncommon in arthritic di+order+ other than cr!+tal depo+ition di+ea+e+ and palindromic rheumati+m that it+ pre+ence i+ hi0hl! +u00e+ti4e of the dia0no+i+. 8nter4al+ &etween attack+ of acute 0out! arthriti+ are of 4aria&le duration. Mo+t untreated patient+ with 0out will e.perience a +econd epi+ode within two !ear+. A+ an e.ample, one lar0e 0roup of patient+ +tudied prior to effecti4e antih!peruricemic *urate?lowerin0, therap! found that >" percent of patient+ had a +econd attack within the fir+t !ear, D@ percent within two !ear+, and G' percent within $# !ear+ 9<#:. /he trend amon0 untreated patient+ i+ toward recurrent acute attack+ that occur after pro0re++i4el! +horter a+!mptomatic period+, and are increa+in0l! prolon0ed and di+a&lin0, pol!articular, and a++ociated with fe4er. Pol!articular flare+ of 0out! arthriti+ ma! occur in a +e6uential *mi0rator!, pattern, +imultaneou+l!, or ma! in4ol4e a clu+ter of ad;acent ;oint+, tendon+ and &ur+ae. Bon! ero+ion+ and deformitie+ can de4elop *chronic 0out! arthropath!,, re+ultin0 in the di+appearance of intercritical period+. /hi+ +ta0e of chronic 0out! arthropath! i+ often accompanied &! tophaceou+ depo+it+ that contri&ute to deformit! and di+a&ilit!. *See E2hronic tophaceou+ 0outE &elow., Evaluation ( /he a4aila&ilit! of effecti4e mean+ to control h!peruricemia ha+ led to +u&+tantial reduction+ in the rate+ of recurrence of 0out! arthriti+ and of tophi in patient+ adherent to lon0?term urate?lowerin0 therap! 9$D:. /he initial

recurrence of 0out! arthriti+ and of tophi in patient+ adherent to lon0?term urate?lowerin0 therap! 9$D:. /he initial intercritical period pro4ide+ an e.cellent opportunit! to do the followin01 A+ta&li+h the dia0no+i+ of 0out if thi+ ha+ not &een accompli+hed durin0 the acute attack. *See EDia0no+i+ of intercritical or chronic tophaceou+ 0outE&elow., 8dentif! and relie4e re4er+i&le cau+e+ of h!peruricemia, potentiall! o&4iatin0 the need for lon0 term urate?lowerin0 therap!. 2la++if! the patient with re0ard to the mechani+m underl!in0 h!peruricemia and 0out, includin0 the cau+e+ of +econdar! h!peruricemia due to o4erproduction or undere.cretion *ta&le $ and ta&le ",. *See E2la++ificationE a&o4e and 5A+!mptomatic h!peruricemia5., 8n+titute proph!lactic anti?inflammator! and urate?lowerin0 therap!, if indicated. /he pre4ention of recurrent 0out i+ di+cu++ed +eparatel!. *See 5Pre4ention of recurrent 0out5., A4aluate the patient for, and, if appropriate, initiate mana0ement of comor&iditie+ common in 0out patient+ *+uch a+ h!perten+ion, chronic renal functional impairment, cardio4a+cular di+ea+e, and the component+ of the meta&olic +!ndrome, 9 <$:. 8n the conte.t of the+e comor&iditie+, a+ well a+ for the aim of +ome de0ree of +erum urate reduction, life+t!le chan0e+ +hould &e re4iewed with the patient 9 "","<,"=:. /he+e mi0ht include chan0e+ in dietar! intake and compo+ition, reduction of alcohol intake, reduction to ideal &od! wei0ht, and dietar! +upplementation, +uch a+ with 4itamin 2. *See 5Pre4ention of recurrent 0out5., C)&'%$C '*)ACE'(S .'( ( /ophaceou+ 0out i+ characteri-ed &! collection+ of +olid urate in connecti4e ti++ue+ *which ma! occa+ionall! &e calcified,. 7hile the+e collection+ ma! &e apparent clinicall! or detected with plain radio0raph!, ultra+ono0raph!, or ma0netic re+onance *MR, ima0in0, it i+ likel! that man! patient+ with 0out and +u+tained h!peruricemia ha4e a much lar0er &urden of clinicall! inapparent urate cr!+tal depo+it+ than i+ +u+pected. Clinical appearance ( /ophi are 4i+i&le andCor palpa&le and can &e pre+ent on the ear+ or in the +oft ti++ue+ includin0 picture $,. /ophi are t!picall! not painful or tender. /he! ma! attenuate the +kin articular +tructure+, &ur+ae, or &one * re4ealin0 a !ellow or white color. On the ear the! do not tran+illuminate. Howe4er, a chronic 0ranulomatou+ inflammator! re+pon+e i+ identifia&le on hi+tolo0ical e.amination of the le+ion+, and, on occa+ion, acute inflammation mimickin0 that of 0out! arthriti+ occur+ in one or +e4eral tophi *picture ",. /he inflammation ma! e.tend &e!ond the confine+ of a +in0le ;oint, producin0 0enerali-ed enlar0ement of a di0it due to the pre+ence of tophi andCor the inflammation it+elf. /he appearance ma! &e +imilar to dact!liti+ +een in other di+order+, +uch a+ p+oriatic arthriti+, other +pond!loarthropathie+, and +arcoido+i+. /he e.pan+i4e and de+tructi4e chan0e+ a++ociated with tophaceou+ 0out ma! &e mi+taken for o+teom!eliti+ * picture ', and ha4e +ometime+ led to erroneou+ amputation of in4ol4ed di0it+ 9<":. /he clinical picture of chronic tophaceou+ 0out ma! &e confu+ed with other form+ of chronic inflammator! pol!arthriti+ +uch a+ rheumatoid arthriti+ *particularl! if tophi are mi+taken for rheumatoid nodule+,. 8n the+e circum+tance+, the a+!mmetr! and a+!nchron! of ;oint in4ol4ement in 0out, the pre+ence of urate cr!+tal+ in the nodular le+ion+, and the di+tincti4e radio0raphic feature+ will often +uffice to di+tin0ui+h &etween the+e di+order+. $maging ( Bone ero+ion+ due to tophi ma! ha4e characteri+tic delicate 5o4erhan0in05 ed0e+. /he characteri+tic+ of tophi on ma0netic re+onance *MR, ima0e+ include relati4el! homo0eneou+ intermediate to low +i0nal on /$?wei0hted ima0e+, and /"?wei0hted ima0e+ that ha4e 4aria&le +i0nal inten+it! 9 <':. Aither homo0eneou+ or peripheral enhancement ma! occur with the addition of 0adolinium. /ophu+ +i-e can &e e+timated on MR ima0in0 9 <<:, or 6uantified &! dual ener0! 2/, &ut the clinical u+efulne++ of +uch information i+ uncertain. 3ltra+ound e.amination directed to ;oint+ or +oft ti++ue depo+it+ i+ an increa+in0l! promi+in0 modalit! for the earl! detection and monitorin0 of therap! for 0out 9<=:. 2haracteri+tic line+ o4erl!in0 the +urface of ;oint cartila0e can &e 4er! +u00e+ti4e. Course ( Prior to the a4aila&ilit! of effecti4e urate?lowerin0 treatment, the inter4al from the fir+t 0out! attack to the on+et of chronic arthriti+ or detecta&le tophi a4era0ed a&out $" !ear+, althou0h inter4al+ ran0in0 from le++ than = !ear+ to <# !ear+ were noted in indi4idual patient+. 8n the era precedin0 the a4aila&ilit! of effecti4e urate?lowerin0 treatment, duration of 0out and de0ree of h!peruricemia were correlated with the rate and e.tent of tophu+ formation. After "# !ear+ of untreated 0out, almo+t D= percent of patient+ were affected, with the hi0he+t pre4alence in patient+ with the hi0he+t +erum urate concentration+ 9<>:. 8n contra+t to the cla++ic pre+entation, a num&er of report+ ha4e de+cri&ed patient+ with tophaceou+ depo+it+ in the a&+ence of, or prior to, 0out! arthriti+, a pre+entation that wa+ pre4iou+l! con+idered a rare occurrence re+tricted to patient+ with uric acid o4erproduction due to m!eloproliferati4e di+order+ or hereditar! en-!me defect+ 9<D,<@:. Althou0h thi+ +ituation ma! in part reflect increa+in0 reco0nition that tophi can form in an! area containin0 connecti4e ti++ue *includin0 the menin0e+ &ut not the &rain and +pinal cord,, ri+k factor+ +imilar to tho+e accountin0 for cr!ptic 0out in elderl! patient+ ma! contri&ute to tophu+ formation a+ the fir+t +i0n of 0out. Such patient+ are more likel! to &e women, to ha4e predominant or e.clu+i4e in4ol4ement of the fin0er+, to ha4e chronic kidne! di+ea+e, and to &e treated with a diuretic or antiinflammator! dru0 9<@:. 3rate?lowerin0 treatment of 0out with urico+uric a0ent+ and allopurinol initiall! led to a dramatic reduction in chronic 0out! arthriti+ and tophaceou+ 0out, with a pre4alence of le++ than = percent reported in +ome +erie+ 9$D:. Howe4er, the+e pro0re++i4e form+ of 0out are &ein0 +een more fre6uentl! once a0ain in certain +u&0roup+ of patient+1

Re+idual pre4alence+ of chronic pol!articular and tophaceou+ 0out approachin0 =# percent ha4e &een reported in +ome +erie+ of men with 0out who+e ma;or ri+k factor+ were e.ce++i4e alcohol con+umption, diuretic u+e, and, mo+t important, +u&optimal mana0ement or poor patient compliance 9<,=:. A more compliant 0roup of elderl! patient+ *mo+t often women, i+ prone to de4elop pol!articular and tophaceou+ 0out in o+teoarthritic ;oint+ a+ illu+trated &! the followin0 o&+er4ation+1 8n one report, @ of ># patient+ with 0out were elderl! women *mean a0e @" !ear+,, all of whom were recei4in0 diuretic therap!B mo+t had tophi in o+teoarthritic interphalan0eal ;oint+ 9 @:. 8n a +econd +erie+, $D percent of $<G patient+ with o+teoarthriti+ had 0out, often with low?0rade inflammation, in o+teoarthritic fin0er ;oint+ 9'$:. /he+e patient+ were elderl! *mean a0e D$ !ear+, and were e4enl! di+tri&uted in 0ender. O4er D# percent were recei4in0 diuretic+, ># percent had impaired renal function, and the mean +erum urate concentration wa+ $$ m0CdL *>=< micromolCL,. /he triad of diuretic?induced h!peruricemia, renal in+ufficienc!, and nodal o+teoarthriti+ plu+ o4errepre+entation of women repre+ent+ a di+tinctl! different pre+entation from the cla++icall! de+cri&ed 0roup of middle a0ed men with tophaceou+ 0out who ha4e a hi0her incidence of h!perten+ion, o&e+it!, and ethanol a&u+e. Or0an tran+plant recipient+ treated with c!clo+porine *and often diuretic+ a+ well, are at increa+ed ri+k for the accelerated de4elopment of chronic tophaceou+ 0out 9 G,$#:. Both renal and cardiac tran+plant recipient+, particularl! tho+e with compromi+ed renal function, ha4e de4eloped +e4ere and often difficult to mana0e complication+ of the h!peruricemic effect of c!clo+porine, which i+ due to impaired urate e.cretion 9G:. *See 5H!peruricemia and 0out in renal tran+plant recipient+5 ., Other patient+ at increa+ed ri+k for chronic tophaceou+ 0out are tho+e who ha4e chronic kidne! di+ea+e that ha+ precluded full?do+e antih!peruricemic dru0 therap!, tho+e who are aller0ic to or intolerant of urate?lowerin0 a0ent+, and tho+e recei4in0 do+e+ of urate?lowerin0 a0ent+ that are inade6uate to achie4e 0oal +erum urate le4el+ in a ran0e &elow the limit of urate +olu&ilit! *often recommended a+ J> m0CdL 9'=D micromolCL:, 9 <G:. &E%AL C'"*L$CA $'%S ', C)&'%$C )-*E&(&$CE"$A ( /here are two ma;or renal complication+ of chronic h!peruricemia1 nephrolithia+i+ and chronic urate nephropath!. %ephrolithiasis ( 3ric acid +tone+ are a ma;or component of the mor&idit! +uffered &! patient+ with 0out. Pure uric acid +tone+ account for onl! = to $# percent of all urinar! tract +tone+ in the 3nited State+ and Aurope, &ut compri+e <# percent or more of +tone+ in area+ with hot, arid climate+ in which the tendenc! to a low urine 4olume and acid urine pH promote uric acid precipitation. *See 53ric acid nephrolithia+i+5., /he pre4alence of uric acid +tone+ amon0 patient+ with 0out prior to effecti4e antih!peruricemic treatment wa+ a&out "# percent, +e4eral hundred?fold 0reater than that in the adult non0out! population. More than @# percent of calculi in patient+ with 0out are compo+ed entirel! of uric acid, with the remainder containin0 calcium o.alate or calcium pho+phate +urroundin0 a central nidu+ of uric acid. /here are three ma;or ri+k factor+ for uric acid nephrolithia+i+1 8ncrea+ed uric acid e.cretion Reduced urine 4olume Low urine pH, a +ettin0 in which mo+t of the uric acid e.i+t+ a+ the un?ioni-ed, more in+olu&le uric acid form rather than a+ the di++ociated, more +olu&le urate anion form. Chronic urate nephropathy ( Renal impairment i+ common amon0 patient+ with 0out, &ut u+uall! reflect+ the coe.i+tence of other di+order+ +uch a+ h!perten+ion, dia&ete+ mellitu+, o&e+it!, athero+clero+i+ 9 <$,=#,=$:, or, in +ome in+tance+, lead into.ication re+ultin0 from u+e of un&onded whi+ke! *moon+hine, 9 =",=':. 8n addition, urate cr!+tal+ can depo+it in the renal medullar! inter+titium, producin0 a chronic inflammator! *tophaceou+, reaction, and 4ar!in0 de0ree+ of fi&ro+i+. /he clinical manife+tation+ of what ha+ &een called chronic urate nephropath! are an ele4ated +erum creatinine, a &land urine +ediment, and h!peruricemia out of proportion to the de0ree of renal in+ufficienc! 9=<:. *See 53ric acid renal di+ea+e+5, +ection on E2hronic urate nephropath!E., D$A.%'S$S ', $% E&C&$ $CAL '& C)&'%$C '*)ACE'(S .'( ( A4en durin0 the a+!mptomatic intercritical period, e.tracellular urate cr!+tal+ are identifia&le in +!no4ial fluid from pre4iou+l! affected ;oint+ in 4irtuall! all untreated 0out! patient+ and appro.imatel! D# percent of tho+e recei4in0 uric acid?lowerin0 therap! 9==?=D:. /hi+ allow+ late e+ta&li+hment of the dia0no+i+ in the ma;orit! of patient+ in whom the dia0no+i+ wa+ not made in the acute +ettin0. /he hi0h pre4alence of urate cr!+tal+ in a+pirate+ from ;oint+ pre4iou+l! affected onl! once +upport+ the 4iew noted a&o4e that, in mo+t in+tance+, depo+ition of urate cr!+tal+ in and a&out ;oint+ precede+ the fir+t clinical epi+ode of 0out &! a +u&+tantial period of time. Demon+tration of urate cr!+tal+ in a+pirate+ of tophaceou+ depo+it+ pro4ide+ a con4enient and +pecific mean+ to corro&orate the dia0no+i+ in the +mall proportion of 0out! indi4idual+ with tophi 9=@:. )istologic e1amination ( 8deall!, ti++ue+ that are &ein0 prepared for hi+tolo0ic e.amination for urate cr!+tal+ +hould &e e.amined a+ fre+h or fro-en +ection+, or pre+er4ed in alcohol *rather than in formalin, and later +tained with a nona6ueou+ +!+tem +uch a+ 7ri0ht?)iem+a +tain. Howe4er, formalin fi.ed, paraffin em&edded ti++ue ha+ &een reported to +till ha4e demon+tra&le &irefrin0ent urate cr!+tal+ if +tained with a nona6ueou+ techni6ue u+in0 alcoholic eo+in 9 =G:.

to +till ha4e demon+tra&le &irefrin0ent urate cr!+tal+ if +tained with a nona6ueou+ techni6ue u+in0 alcoholic eo+in 9 =G:. A6ueou+ +tain+, +uch a+ hemato.!lin and eo+in, allow urate cr!+tal+ to di++ol4e, lea4in0 &ehind a nondia0no+tic eo+inophilic matri. that ma! ha4e forei0n &od! 0iant cell+. Criteria for clinical diagnosis of intercritical gout ( 8n the a&+ence of the mean+ to identif! urate cr!+tal+ or in the pre+ence of a ne0ati4e polari-ed li0ht micro+copic +tud!, a pro4i+ional dia0no+i+ of 0out i+ made &! a com&ination of clinical and hi+torical criteria. *See E2riteria for clinical dia0no+i+ of 0outE a&o4e., $%,'&"A $'% ,'& *A $E% S ( Aducational material+ on thi+ topic are a4aila&le for patient+. *See 5Patient information1 )out5., 7e encoura0e !ou to print or e?mail thi+ topic, or to refer patient+ to our pu&lic we& +ite, www.uptodate.comCpatient+ , which include+ thi+ and other topic+. 3+e of 3p/oDate i+ +u&;ect to the Su&+cription and Licen+e A0reement

&E,E&E%CES $. ". '. <. =. >. D. @. G. M22AR/L D , HOLLAFDAR L. 8dentification of urate cr!+tal+ in 0out! +!no4ial fluid. Ann 8ntern Med $G>$B =<1<=". Mikul+ /R, %arrar /, Bilker 7B, et al. )out epidemiolo0!1 re+ult+ from the 3M )eneral Practice Re+earch Data&a+e, $GG#?$GGG. Ann Rheum Di+ "##=B ><1">D. Becker MA, 2hohan S. 7e can make 0out mana0ement more +ucce++ful now. 2urr Opin Rheumatol "##@B "#1$>D. Faka!ama DA, Barthelem! 2, 2arrera ), et al. /ophaceou+ 0out1 a clinical and radio0raphic a++e++ment. Arthriti+ Rheum $G@<B "D1<>@. Lawr!, )N88, %an, P/, Blue+tone, R. Pol!articular 4er+u+ monoarticular 0out1 A pro+pecti4e comparati4e anal!+i+ of clinical feature+. Medicine $G@@B >@1''=. Pui0 ), MichOn AD, imPne- ML, et al. %emale 0out. 2linical +pectrum and uric acid meta&oli+m. Arch 8ntern Med $GG$B $=$1D">. Lall! AN, Ho ) r, Maplan SR. /he clinical +pectrum of 0out! arthriti+ in women. Arch 8ntern Med $G@>B $<>1"""$. Macfarlane D), Dieppe PA. Diuretic?induced 0out in elderl! women. Br Rheumatol $G@=B "<1$==. Med $G@GB '"$1"@D. Lin HL, Rocher LL, McQuillan MA, et al. 2!clo+porine?induced h!peruricemia and 0out. F An0l

$#. Burack DA, )riffith BP, /homp+on MA, Mahl LA. H!peruricemia and 0out amon0 heart tran+plant recipient+ recei4in0 c!clo+porine. Am Med $GG"B G"1$<$. $$. Lawrence R2, Helmick 2), Arnett %2, et al. A+timate+ of the pre4alence of arthriti+ and +elected mu+culo+keletal di+order+ in the 3nited State+. Arthriti+ Rheum $GG@B <$1DD@. $". Mramer HM, 2urhan ). /he a++ociation &etween 0out and nephrolithia+i+1 the Fational Health and Futrition A.amination Sur4e! 888, $G@@?$GG<. Am Midne! Di+ "##"B <#1'D. $'. Arromdee A, Michet 2 , 2row+on 2S, et al. Apidemiolo0! of 0out1 i+ the incidence ri+in0R "G1"<#'. $<. 2hoi H. Apidemiolo0! of cr!+tal arthropath!. Rheum Di+ 2lin Forth Am "##>B '"1"==. $=. 7allace ML, Riedel AA, o+eph?Rid0e F, 7ortmann R. 8ncrea+in0 pre4alence of 0out and h!peruricemia o4er $# !ear+ amon0 older adult+ in a mana0ed care population. Rheumatol "##<B '$1$=@". $>. Rodd! A, Shan0 7, Dohert! M. /he chan0in0 epidemiolo0! of 0out. Fat 2lin Pract Rheumatol "##DB '1<<'. $D. OEDuff! D, Hunder )), Mell! P . Decrea+in0 pre4alence of tophaceou+ 0out. Ma!o 2lin Proc $GD=B =#1""D. $@. Lo0an A, Morri+on A, Mc)ill PA. Serum uric acid in acute 0out. Ann Rheum Di+ $GGDB =>1>G>. $G. Schle+in0er F, Baker D), Schumacher HR r. Serum urate durin0 &out+ of acute 0out! arthriti+. "<1"">=. Rheumatol $GGDB Rheumatol "##"B

"#. Park LB, Park LS, Lee S2, et al. 2linical anal!+i+ of 0out! patient+ with normouricaemia at dia0no+i+. Ann Rheum Di+ "##'B >"1G#. "$. Schle+in0er F, For6ui+t M, 7at+on D . Serum urate durin0 acute 0out. Rheumatol "##GB '>1$"@D. "". 2hoi HM, Atkin+on M, Marl+on A7, et al. Alcohol intake and ri+k of incident 0out in men1 a pro+pecti4e +tud!. Lancet "##<B '>'1$"DD. "'. oo+ten LA, Fetea M), M!lona A, et al. An0a0ement of fatt! acid+ with /oll?like receptor " dri4e+ interleukin?$T production 4ia the AS2Cca+pa+e $ pathwa! in mono+odium urate monoh!drate cr!+tal?induced 0out! arthriti+. Arthriti+ Rheum "#$#B >"1'"'D.

"<. 2hoi HM, Liu S, 2urhan ). 8ntake of purine?rich food+, protein, and dair! product+ and relation+hip to +erum le4el+ of uric acid1 the /hird Fational Health and Futrition A.amination Sur4e!. Arthriti+ Rheum "##=B ="1"@'. "=. 2hoi HM, Atkin+on M, Marl+on A7, et al. Purine?rich food+, dair! and protein intake, and the ri+k of 0out in men. F An0l Med "##<B '=#1$#G'. ">. 2hoi HM, 7illett 7, 2urhan ). 2offee con+umption and ri+k of incident 0out in men1 a pro+pecti4e +tud!. Arthriti+ Rheum "##DB =>1"#<G. "D. 2hoi HM, 2urhan ). 2offee, tea, and caffeine con+umption and +erum uric acid le4el1 the third national health and nutrition e.amination +ur4e!. Arthriti+ Rheum "##DB =D1@$>. "@. Simkin PA. /he patho0ene+i+ of poda0ra. Ann 8ntern Med $GDDB @>1"'#.

"G. Mc2art! D . )out without h!peruricemia. AMA $GG<B "D$1'#". '#. Simkin PA, 2amp&ell PM, Lar+on AB. )out in He&erdenE+ node+. Arthriti+ Rheum $G@'B ">1G<. '$. Lall! AN, Simmermann B, Ho ) r, Maplan SR. 3rate?mediated inflammation in nodal o+teoarthriti+1 clinical and roent0eno0raphic correlation+. Arthriti+ Rheum $G@GB '"1@>. '". 7allace SL, Ro&in+on H, Ma+i A/, et al. Preliminar! criteria for the cla++ification of the acute arthriti+ of primar! 0out. Arthriti+ Rheum $GDDB "#1@G=. ''. 2hen LU, Schumacher HR. 2urrent trend+ in cr!+tal identification. 2urr Opin Rheumatol "##>B $@1$D$. '<. Pa+cual A. )out update1 from la& to the clinic and &ack. 2urr Opin Rheumatol "###B $"1"$'. '=. Shan0 7, Dohert! M, Pa+cual A, et al. A3LAR e4idence &a+ed recommendation+ for 0out. Part 81 Dia0no+i+. Report of a ta+k force of the Standin0 2ommittee for 8nternational 2linical Studie+ 8ncludin0 /herapeutic+ *AS28S8/,. Ann Rheum Di+ "##>B >=1$'#$. '>. an++en+ H , %ran+en , 4an de Li+donk AH, et al. A dia0no+tic rule for acute 0out! arthriti+ in primar! care without ;oint fluid anal!+i+. Arch 8ntern Med "#$#B $D#1$$"#.

'D. Dal&eth, F, Ha+kard, DO. Pathoph!+iolo0! of cr!+tal?induced arthriti+. 8n1 2r!+tal?induced Arthropathie+, 7ortmann, RL, Schumacher, HR r, Becker, MA, R!an, LM *Ad+,, /a!lor V %ranci+, Few Lork "##>. p "'G. '@. Mc2art!, D . S!no4ial fluid. 8n1 Arthriti+ and Allied 2ondition+, $<th ed, Moopman, 7 , *Ad,, Lippincott 7illiam+ and 7ilkin+, Philadelphia "##$. p.@'. 'G. Schumacher HR, Smol!o AP, /+e RL, Maurer M. Arthriti+ a++ociated with apatite cr!+tal+. Ann 8ntern Med $GDDB @D1<$$. <#. )utman, AB. )out and 0out! arthriti+. 8n1 /e.t&ook of Medicine, Bee+on, PB, McDermott, 7 *Ad+,, Saunder+, Philadelphia $G=@. p.=G=. <$. Becker MA, oll! M. H!peruricemia and a++ociated di+ea+e+. Rheum Di+ 2lin Forth Am "##>B '"1"D=. <". Rou++eau 8, 2ardinal A A, Ra!mond?/rem&la! D, et al. )out1 radio0raphic findin0+ mimickin0 infection. Skeletal Radiol "##$B '#1=>=. <'. H+u 2L, Shih //, Huan0 MM, et al. /ophaceou+ 0out of the +pine1 MR ima0in0 feature+. 2lin Radiol "##"B =D1G$G. <<. Schumacher HR r, Becker MA, Adward+ FL, et al. Ma0netic re+onance ima0in0 in the 6uantitati4e a++e++ment of 0out! tophi. 8nt 2lin Pract "##>B >#1<#@. <=. /hiele R), Schle+in0er F. Dia0no+i+ of 0out &! ultra+ound. Rheumatolo0! *O.ford, "##DB <>1$$$>. <>. )utman AB. /he pa+t four decade+ of pro0re++ in the knowled0e of 0out, with an a++e++ment of the pre+ent +tatu+. Arthriti+ Rheum $GD'B $>1<'$. <D. Hollin0worth P, Scott /, Burr! H2. Fonarticular 0out1 h!peruricemia and tophu+ formation without 0out! arthriti+. Arthriti+ Rheum $G@'B ">1G@. <@. 7ernick R, 7inkler 2, 2amp&ell S. /ophi a+ the initial manife+tation of 0out. Report of +i. ca+e+ and re4iew of the literature. Arch 8ntern Med $GG"B $="1@D'. <G. Shan0 7, Dohert! M, Bardin /, et al. A3LAR e4idence &a+ed recommendation+ for 0out. Part 881 Mana0ement. Report of a ta+k force of the A3LAR Standin0 2ommittee for 8nternational 2linical Studie+ 8ncludin0 /herapeutic+ *AS28S8/,. Ann Rheum Di+ "##>B >=1$'$". =#. Ber0er L, LW /%. Renal function in 0out. 8N. An anal!+i+ of ="< 0out! +u&;ect+ includin0 lon0?term follow?up +tudie+. Am Med $GD=B =G1>#=. =$. /ALBO// H, /ARPLAF ML. /he kidne! in 0out. Medicine *Baltimore, $G>#B 'G1<#=. =". Batuman N, Mae+aka M, Haddad B, et al. /he role of lead in 0out nephropath!. F An0l Med $G@$B '#<1="#. ='. 2ra+well P7, Price , Bo!le PD, et al. 2hronic renal failure with 0out1 a marker of chronic lead poi+onin0. Midne! 8nt $G@<B ">1'$G. =<. Beck LH. Re6uiem for 0out! nephropath!. Midne! 8nt $G@>B '#1"@#. ==. Pa+cual A. /he dia0no+i+ of 0out and 2PPD cr!+tal arthropath!. Br Rheumatol $GG>B '=1'#>. =>. Pa+cual A, Batlle?)ualda A, MartXne- A, et al. S!no4ial fluid anal!+i+ for dia0no+i+ of intercritical 0out. Ann 8ntern Med $GGGB $'$1D=>. =D. A0udelo 2A, 7ein&er0er A, Schumacher HR, et al. Definiti4e dia0no+i+ of 0out &! identification of urate cr!+tal+ in a+!mptomatic metatar+ophalan0eal ;oint+. Arthriti+ Rheum $GDGB ""1==G. =@. Re0e , Shet /, Faik L. %ine needle a+piration of tophi for cr!+tal identification in pro&lematic ca+e+ of 0out. A report of two ca+e+. Acta 2!tol "###B <<1<''. =G. Shidham N, 2hi4ukula M, Ba+ir S, Shidham ). A4aluation of cr!+tal+ in formalin?fi.ed, paraffin?em&edded ti++ue +ection+ for the differential dia0no+i+ of p+eudo0out, 0out, and tumoral calcino+i+. Mod Pathol "##$B $<1@#>.

.&A*)$CS

ophus of the /nee

Lar0e tophu+ of the knee in patient with chronic uncontrolled 0out. Courtesy of Peter H Schur, MD.

$nflamed tophaceous gout

/hree inflamed tophi o4er the pro.imal interphalan0eal ;oint+ in a patient with chronic tophaceou+ 0out. Se4eral of the le+ion+ ruptured +pontaneou+l! o4er the ne.t three da!+, e.udin0 a pa+t! material compo+ed of urate cr!+tal+ and inflammator! cell+ &ut no or0ani+m+. /he inflammation lar0el! +u&+ided o4er one week after the admini+tration of a non+teroidal antiinflammator! dru0. Courtesy of Michael A Becker, MD.

.out of the foot

Plain radio0raph of the foot demon+tratin0 feature+ con+i+tent with 0out. /here i+ +oft ti++ue +wellin0 and e.ten+i4e ero+ion+ in4ol4in0 the fir+t metatar+ophalan0eal ;oint, a+ well a+ calcification+ within a tophu+. Courtesy of Jonathan Kruskal, MD.

Causes of secondary hyperuricemia due to increased purine 2iosynthesis and3or urate production $nherited en0yme defects leading to purine overproduction

H!po.anthine?0uanine pho+phori&o+!ltran+fera+e deficienc! Pho+phori&o+!lp!ropho+phate +!ntheta+e o4eracti4it! )luco+e?>?pho+phata+e deficienc! *0l!co0en +tora0e di+ea+e, t!pe 8,

Clinical disorders leading to purine and3or urate overproduction

M!eloproliferati4e di+order+ L!mphoproliferati4e di+order+ Mali0nancie+ Hemol!tic di+order+ P+oria+i+ O&e+it! /i++ue h!po.ia Down +!ndrome )l!co0en +tora0e di+ea+e+ *t!pe+ 888, N, N88,

Drug45 diet45 or to1in4induced purine and3or urate overproduction

Athanol A.ce++i4e dietar! purine in0e+tion Pancreatic e.tract %ructo+e Nitamin B$" deficienc! Ficotinic acid Ath!lamino?$,',<?thiadia-ole <?amino?=?imida-ole car&o.amide ri&o+ide 2!toto.ic dru0+ 7arfarin

Causes of secondary hyperuricemia due to decreased renal clearance Clinical disorders

2hronic renal in+ufficienc! of an! form Lead nephropath! *+aturnine 0out, Affecti4e 4olume depletion *e0, fluid lo++e+, heart failure, Dia&etic or +tar4ation ketoacido+i+ Lactic acido+i+ Preeclamp+ia O&e+it! H!perparath!roidi+m H!poth!roidi+m Sarcoido+i+ 2hronic &er!llium di+ea+e

%amilial ;u4enile h!peruricemic nephropath! *% HF, Medullar! c!+tic kidne! di+ea+e *M2MD, )lomeruloc!+tic kidne! di+ea+e

Drug4 or diet4induced
Diuretic+ *thia-ide+ and loop diuretic+, 2!clo+porine and tacrolimu+ Low do+e +alic!late+ Atham&utol P!ra-inamide Athanol Le4odopa Metho.!flurane La.ati4e a&u+e *alkalo+i+, Salt re+triction

Crystal4induced arthritis Characteristic .out

$.= to ".> ca+e+ per $### indi4idual+B increa+e+ with a0e in men and po+tmenopau+al womenB $=C$### at a0e =@B men1 "@C$###, women1 $$C$### Mono+odium urate Fe0ati4el! &irefrin0entB needle?+haped Monoarticular I oli0oarticularB pol!articular J'# percent %ir+t M/P ;oint Mo+t fre6uentl! affected ;oint+
8nitiall! =# percent A4entuall! G# percent

*seudogout

Pre4alence

J$ ca+e per $### indi4idual+B increa+e+ with a0e

2r!+tal+ chemi+tr! Appearance

2alcium p!ropho+phate dih!drate 7eakl! po+iti4el! &irefrin0entB linear or rhom&oidal Monoarticular I oli0oarticular

Articular in4ol4ement

Mnee, wri+t, other

Ankle, knee+, other Predi+po+in0 condition+Cri+k factor+ H!peruricemiaY, o&e+it!, h!perten+ion, h!perlipidemia, alcohol in0e+tion, lead in0e+tion, hereditar! en-!me defect Acute attack+1
FSA8D+, cortico+teroid+, colchicine

H!poth!roidi+m, hemochromato+i+, OA, chronic renal in+ufficienc!, dia&ete+, h!perparath!roidi+m, hereditar! *rare, Acute attack+1
FSA8D+, cortico+teroid+, colchicine

/herapeutic option+ 2hronic mana0ement

3rate?lowerin0 a0ent+, colchicine

2hronic mana0ement
FSA8D+ Z colchicine

Y Dru0+ a++ociated with h!peruricemia include diuretic+, low?do+e +alic!late+, nicotinic acid, c!clo+porine, ethanol and etham&utol. Adapted from Am J Med !""#$ !%& '(S.

[ "#$$ 3p/oDate, 8nc. All ri0ht+ re+er4ed. | Su&+cription and Licen+e A0reement Licen+ed to1 meddics apuntes de medicina