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Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_2821_Библиотеки_им_академика_М_И_Перельмана
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enthesis—theregionwhereatendonorligamentinsertsintobone.
HLA-B27 is an MHC class I molecule that is suspected to play a role in presenting
antigensthatcantriggerautoimmunity.AlthoughHLA-B27ispresentinapproximately8%of
thegeneralpopulation,itispresentingreaterthan90%ofpatientswithankylosingspondylitis,
30%to70%ofpatientswitheitherreactivearthritisorinflammatoryboweldisease,40%to
50% ofpatientswith PsA,and70% ofpatientswith undifferentiated spondyloarthropathy.
23
However,because the incidenceof spondyloarthropathyis approximately 1% in the general
population,itisimportanttorememberthatlessthan10%ofpeoplewithHLA-B27develop
spondyloarthropathy.
Ingeneral,thepatternofarthritisinspondyloarthropathytendstobeasymmetric,involving
mediumandlargejoints,andinvolvingfourorlessjoints(oligoarthritis).Makingthediagnosis
is difficult because there are no reliable blood tests for the conditions and because the
radiologicfindingsmaytakedecadestodevelop.Becausethesepatientstendtopresentintheir
secondthroughfifthdecadesoflife,manypatientsareactiveandwilloftenattributetheirjoint
painstowhateverphysicalactivitytheyhaverecentlybeenperforming.Theymayreportthat
their injuryhas taken longer than expectedto heal, or they may reportthat they have been
repeatedlygettinginjured.Jointswelling,morningstiffness,theinvolvementofmultiplejoints,
a family history of psoriasis or inflammatory bowel disease, and a history of a favorable
response of the joint pain to oral corticosteroids may all be clues to the presence of a
spondyloarthropathy.Thespondyloarthropathiesmaypresentwithsystemicsymptoms,butthis
isnotaprevalentfeatureasitisinrheumatoidarthritisandlupus.
Enthesitis(Fig.2-3) is acommonfeatureinallspondyloarthropathies, asseveralstudies
have demonstrated. For example, in the study of D’Agostino et al.,24 164 patients with
spondyloarthropathy were compared with 34 controls (mechanical low back pain, and 30
rheumatoidarthritispatients).Foreachpatient,thefollowingregionswerescannedusinggray
scale and power Doppler ultrasound: greater trochanter of the hip, plantar fascia, patellar
ligament, quadriceps tendon, pubis, Achilles tendon, medial and lateral epicondyles of the
elbow,andtibialisanteriorinsertion.Thepresenceoferosionsatthetendoninsertionandthe
presence of power Doppler signal within the tendon allowed significant discrimination of
spondyloarthropathy(SpA)patientsfromcontrols; 81% of SpApatients hadpower doppler
(PD)signalinatleastoneenthesis,whereaszerocontrolshadPDsignal;19%ofSpApatients
haderosionscomparedwithnocontrolsthathaderosions.InthestudyofD’Agostinoetal.,
25
powerDopplersignalatbaselineinatleastoneenthesiswasthebestpredictorofSpAat2
years. Dactylitis is another clinical finding that tends to be associated with
spondyloarthropathy.Patientswhohavethisphenotypedevelopswellingofeitheratoeora
fingerthroughouttheentirelengthofthedigitsuchthatitappearstoresembleasausage.
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FIGURE2-3.Enthesitis.Longitudinal(AandC)andshortaxis(BandD)viewsofthedistalAchillestendon(AT)as
itinsertsinthecalcaneus(Cal).Leftsideisproximalandmedial.Thereisslightthickeningofthetendonasitinserts
intothecalcaneus,andanerosionisseen(star).PowerDopplersignal,indicatinginflammation,isseenwithinthe
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erosion.
AnkylosingSpondylitis
This isaconditionthatischaracterizedbysacroiliitisandfusionofthesacroiliacjoints as
wellasthe spine,whichusuallytakesplace after manyyearsofdisease (Fig.2-4). Patients
presentwithinflammatorybackpainthatisworstinthemorningandimprovesasthedaygoes
on.Often,peripheralsymptomsinanasymmetricdistributionoflargermedianjointsarealso
present. Previous classification criteria have focused on X-ray findings, which may take
decadestodevelop.Therefore,newclassificationcriteriahavebeendeveloped26thatfocuson
acombinationofimagingbyX-rayorMRI,thepresenceofHLA-B27,andclinicalfeatures.In
contrast to rheumatoid arthritis, initiation of therapy begins with NSAIDs, but the
recommendation is to change to TNF blockers if symptoms are not controlled after a few
months. Furthermore, the IL-23/IL-17 cytokine pathway has been recently implicated in
ankylosingspondylitisandotherspondyloarthropathies.Elevatedlevelsofthecytokineshave
beenfoundinthebloodandjointsofthesepatients.Agentsthatblockthis pathwayarenow
availablefortherapy.
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FIGURE2-4.Ankylosingspondylitis.Frontalviewofthepelvis(A)demonstratingfusionofthesacroiliacjoints
bilaterally(arrows).In(B),syndesmophytes(arrowheads)bridgetheanteriorportionsofthecervicalspine.
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PsoriaticArthritis
About30%ofpatientswithpsoriasiswilldevelopPsA,and50%ofthesepatientsmaygoon
todevelopsomejointdeformities.PsAdiffersfromotherspondyloarthropathiesinthatthere
are five clinical patterns of arthritis that may occur in isolation or in overlap with other
phenotypes: an asymmetric oligoarthritis (the typical spondyloarthropathy pattern); a
rheumatoid arthritis–likepresentationwith symmetric polyarthritis ofthe small joints ofthe
hands and feet; distal interphalangeal joint involvement (often with dactylitis), axial
involvement;severedestructiveinvolvementalsoknownasarthritismutilans.PsAmaycoexist
witheithergoutorosteoarthritis,soitisimportanttoruleouttheseconditionspriortomaking
thediagnosis.
In about 15% of patients, the arthritis may precede the joint symptoms. In addition,
psoriasismaybelocatedinregionsthatthepatientmayfailtoappreciateormentionsuchas
thescalp,behindtheears,theumbilicus,thepenis,andtheglutealfold.Psoriaticnailchanges
includingpitting, ridging,andonycholysismayormay not be present.Classificationcriteria
forPsA27includethepresenceofaninflammatoryarthritisplustwoormoreofthefollowing:
evidenceofcurrentpsoriasis,historyofpsoriasisorafirst-orsecond-degreefamilynowwith
psoriasis;naildystrophy;negativeRF;dactylitisorhistoryofdactylitis;X-rayshowingjuxtaarticularnewboneformation.Occasionally,patientswillhaveanelevatedESRorCRP,but
notfrequently.X-rayfindingsmightincludesacroiliitis,pencilandcupdeformityofthefingers
ortoes(awhittlingdowntoapointofthedistalaspectoftheproximalphalanxpairedwitha
flaringoftheproximalportionofthemoredistalphalanxsuchthattheappearanceisthatofa
pencil going into a cup), and erosions. On ultrasound, one may see synovial thickening,
effusion,synovitisortenosynovitis,erosion,orenthesitis.
Treatmentoftheskindiseasedependsonthelocationandseverityandmaybelimitedto
topical therapy or light therapy, with systemic therapy reserved for extensive disease.
Treatmentofthearthritisagaindependsontheseverityofsymptoms.NSAIDsmaybereserved
formilddisease,butmoreaggressivearthritisisusuallytreatedwithafirstlineofDMARD
suchasmethotrexate,followedbyadditionorswitchingtobiologicagentsincludingtheTNF
blockers,ablockeroftheIL-12/23pathway(ustekinumab),oraphosphodiesterase4inhibitor
(apremilast).
CrystallineArthritis
The mostcommon crystallinearthropathies that presentinthelower extremity are gout and
pseudogout. Both entities share the theme of a salt precipitating within a joint and/or
surrounding tissues and triggering a robust inflammatory response. In gout, the salt is
monosodium urate, whereas inpseudogout thesalt is calcium pyrophosphate. On occasion,
bothcrystalsmaybefoundwithinthejoint.Inaddition,the crystalsmaybefoundwithinthe
jointevenintheabsenceofaflareofarthritis. Whenthejointistraumatizedorifthereisa
septic process within the joint, there may be release of the crystals, which then may be
observedinthesynovialfluid.Therefore,thepresenceofcrystalsinasynovialaspiratedoes
notruleoutthepresenceofinfection.
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Gout
Gout is one of the most painful arthropathies and, if untreated, has the potential to be
destructivetoaffectedjoints(Fig.2-5).Oneofthemorecommonlyinvolvedjointsisthe1st
MTP;however,itisimportanttorememberthatspondyloarthropathyandrheumatoidarthritis
mayalsoaffectthisjoint.Theonsetofpainduringaflareofgoutisusuallyrapid;sometimes,
within hours the painlevel can crescendo: oftenpeople cannotbear weight onthe affected
joint. Erythema and swelling are frequently observed. Fever and elevated white count,
althoughnotcommon,canbeassociatedwithsevereflares.Ifgoutisuntreated,itmayprogress
totophaceousgoutinwhichlargedepositsofuricacidgrowtobepalpablebeneaththeskin
andmayerodeintoadjacentbone.Thedorsumofthehandsandfeet,theextensorsurfaceofthe
elbows,andtheearsarecommonlyaffectedlocations.
Goutiscausedbyelevateduricacidinthebloodandtissue.Whentheconcentrationofuric
acid exceeds the limits of solubility, it tends to precipitate as sodium-urate salt in the
extracellulartissues.Thepresenceofahigh uricaciddoesnotguaranteegout;indeed,there
are many patients with very high uric acids who have never had a gout flare. Therefore,
asymptomatic hyperuricemia does not need to be treated prophylactically. When uric acid
crystals precipitate with the joint, they cause acute inflammation as they are ingested by
neutrophils. The crystals may activate complement directly or may stimulate leukocytes to
produceproinflammatorymediatorssuchas IL-1.Goutcrystals maybe identified withinthe
synovialfluidasneedle-shapedcrystalsthatareeitheryelloworblueunderapolarizingfilter.
Whenthe polarizing filter is oriented parallel to the directionof the crystal, itwill appear
yellow;whenthepolarizerfilterisorientedperpendiculartothedirectionofthecrystal,itwill
appearblue.Uricacidisawasteproductofnucleicacidmetabolism,andthesourcesofuric
acidinpatientswithgoutarebothfoodsthatarehighinpurinesandalsofrombreakdownof
the DNA from one’s own cells. In addition, 80% of patients with elevated uric acid have
decreasedexcretionthroughthe kidneys. Alcoholand somemedicationssuch as aspirinand
diureticscanalsodecreaseuricacidexcretioninthekidney,precipitatingaflareofgout.
TypicalX-rayfindingsofgoutincludepunchedouterosionswithoverhangingedgesand
theappearanceoftophiorcollectionsofuricacidcrystals.Thesefindingsmayalsobeseenin
ultrasoundassociatedwithsynovialthickening,effusions,andincreasedpowerDopplersignal
(Fig.2-6).InanarticlepublishedbyThieleandSchlesinger,2837jointsfrom23patientswith
crystal-provengoutwereexaminedbygrayscaleultrasoundandcomparedwith23controls.
The“doublecontoursign”(Fig.2-7) was seenin92% ofthegoutpatientsandnoneofthe
controls. Tophi were observed in all 1st MTPs of gout patients and none of the controls.
Erosionswereseenin65%ofthe1stMTPsofgoutpatientsandonecontrolpatient.
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FIGURE2-5.Gout.Crystalsofuricacidprecipitatewithinthejointorperiarticularstructures,leadingtoactivationof
complementandproductionofcytokinessuchasinterleukin-1,causingarobustacuteinflammatoryresponse.
FIGURE2-6.Examplesofultrasoundfindingsingout.Twolongitudinalviewsofthe1stmetatarsal-phalangeal
goutoverthemedial(A)anddorsal(B)regionsofthejointinapatientwithknowngout.Leftsideisproximal.A
punchedouterosionwithoverhangingedgesisdemonstrated(A)inthe1stmetatarsalhead(star).In(B),adark
regionemanatingfromthejoint,suggestingsynovialthickening,containsabrightpunctatespotsuggestiveofauric
aciddeposit(arrow).MT,metatarsalhead;PP,proximalphalanx.
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MostNSAIDsareeffectiveattreatingacutegout,butoftentheirusemaybeinconflictwith
one ofthe manycomorbidities thatare associated with gout.Colchicineis anold drug that
inhibitsmicrotubuleformationinleukocytesandinterfereswithcellmigration.Itisoftenused
atadoseof1.2mgoncefollowedby0.6mgshortlythereafter.Colchicineisthencontinuedat
0.6mgonceortwicedailyuntilsymptomsresolve.Inaddition,itmaybeusedonanongoing
basis at 0.6 mg once or twice daily as a prophylactic agent to prevent flares. Intravenous
colchicine has the potential to cause severe marrow suppression and so is rarely used.
Corticosteroidssuchasprednisoneandmethylprednisoneareveryeffectiveatcontrollinggout
flaresbothinoralformsandwheninjectedintoasymptomaticjoint.Inpatientswithchronic
goutsymptoms,tophi,oruratenephropathy,uricacid–loweringtherapymaybeinitiatedwith
eitherallopurinolorfebuxostat.Thetargeturicacidinpatientswithchronicgoutislessthan
6.0 mg/dL or less than 5.0 mg/dL in patients with tophi. Uric acid levels equilibrate
approximately2weeksafterchangingthedose ofaurate-loweringagent;therefore,frequent
follow-upisrequiredtotitratethedosetothatwhichachievesthedesiredlevelofuricacid.
Pseudogout(CalciumPyrophosphateDeposition)
Pseudogout is similar to gout in that symptoms are also caused by a salt, calcium
pyrophosphate,whichhasdepositedwithinjointsandsurroundingtissues.Likegoutcrystals,
pseudogoutcrystalsmayalsobeobservedwithinjointaspirates;however,thecrystalsappear
rhomboidshapedandhaveablueappearancewhentheyareorientedparalleltothepolarizing
filter.Pseudogout can take either an acute or a chronic form. When patients have anacute
pseudogoutflare,the commonjointsinvolvedarethe kneesandwrists.Becausepseudogout
crystalscontaincalcium,theyaremoreeasilyseenonX-raysthangoutcrystalsandoftenmay
beobservedinthekneesandwrist.InthestudyofFilippouetal.,2942crystal-provencalcium
pyrophosphatedihydrate(CPPD)patientswereexaminedbygrayscaleultrasound.Themost
frequently observed sites for CPPD were the femoral condyle of the knee (Fig. 2-7), the
menisci, and the triangular fibrocartilage complex of the wrist. Occasionally, calcium
pyrophosphatemaybeseensurroundingthedensofthe2ndcervicalvertebrae.Thismaycause
headaches and/or neck pain and is called crowded dens syndrome—diagnosis is made by
computerizedaxialtomographyscanofthecervicalspine.Riskfactorsforpseudogoutinclude
ochronosis, hyperparathyroidism, thyroid abnormalities, hemochromatosis, Wilson disease,
hypophosphatemia, and hypomagnesemia. Treatment of pseudogout is more challenging than
goutbecausethereare noagentstoreducethecrystal burden.Therapy is usuallylimited to
NSAIDs,corticosteroids,andcolchicine.
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FIGURE2-7.Ultrasoundfindingsincrystallinearthropathy:Axial(AandB)andsagittal(C)viewsoftheanterior
kneeinfullflexiontoexposethearticularcartilage(AC).Leftsideismedial(AandB)orproximal(C).Anormalknee
isshownin(A).Image(B)demonstratesthedoublecontoursignobservedingout,abrightbandsuperficialtothe
articularcartilage(arrowheads).Image(C)demonstratesdepositionofcalciumpyrophosphatecrystalswithin
articularcartilage(arrows).(ImageskindlyprovidedbyDr.LisaVasanthandDr.JonathanSamuels.)
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CONCLUSIONS
Rheumatic diseases of the lower extremity maypresent in a similar fashion to mechanical
problems.Itisimportanttoidentifytheseconditionsearlybecausesomehavethepotentialto
causepermanentdamagewithoutappropriatetherapy.Newtherapieshaverevolutionizedthe
treatments of these conditions. Clues to a systemic illness may be found in associated
symptomsoronthephysicalexamination;therefore,itisimportanttoalwaysperformacareful
history and physical examination when inflammatory disease is suspected. In addition, the
growing useofMSKUSismaking earlyandmore accuratediagnosispossible. Some ofthe
more common rheumatic diseases that may be observed in the lower extremity include
rheumatoidarthritis,spondyloarthropathies,andcrystallinearthropathies.
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