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exercise, physical therapy, and surgery. A recent Cochrane review examiningthe effects of
dietarymanipulationonsymptomreliefinpatientswithRA concluded thatdueprimarilyto
study size limitations, the effects are still uncertain.10 Pharmacologic therapies include
nonsteroidal anti-inflammatory drugs (NSAIDs), oral and injected corticosteroids, diseasemodifyingantirheumatologicdrugs(DMARDs), andimmunosuppressive agents.Althoughthe
American College of Rheumatology released its updated recommendations for the
pharmacologic approach to treating RA,11 most patients would benefit from a treatment
regimenthatincorporatesseveralpharmacologicandnonpharmacologicapproaches.
ACUTELOWEREXTREMITYPATHOLOGIC
FRACTURESSECONDARYTOMETASTATIC
MALIGNANTDISEASE
Malignant diseases include both “solid” tumors arising in tissue parenchyma and “liquid”
tumorsarising in thebloodstream.Spread ofcancerousmetastases tobone iscommon with
primarylung,prostate,kidney, thyroid, andbreastmalignancies12;bonyinvolvementis also
common inmultiplemyeloma,andcanbeseeninassociationwithlymphoma andleukemia.
Althoughbenignbonelesionscanalsocompromisethestructuralintegrityofbonescomprising
the appendicular skeleton, metastatic malignant disease must always be considered with
suddentransversefemoralortibialfracturesprecipitatedbyapplicationofminimalforce.
Malignancies metastatic to bone may weaken its architecture, often by stimulating
osteoclaststhatbreakdownhealthybonetissueandreleasecalciumintotheblood.Metastases
canalso stimulateosteoblastic activity, causing abnormal bonegrowth. Diseased bone may
have focal points of weakness, where minimal rather than substantial force may prove
sufficienttofracturelongbones.
Presentation
Patientswilltypicallypresentcomplainingoflongbonedeformityandseverepain,suddenin
onset after exposure to minimal force. Patients mayreport occurrence during an otherwise
normal preceding activity, such as jogging, walking, or cutting to change direction while
running.Patientswithpathologiclowerextremityfracturesmayreportsuddenlyfallingdown,
withsubsequentinabilitytoambulate.Somepatientswillbeunawareofanunderlyingcancer
diagnosisatthetimeofpresentation;therefore,theclinician’sindexofsuspicionmustremain
highwhencaringforpatientswithlongbonefractureswhogiveahistoryofminimalpreceding
trauma.
SignsandSymptoms
Beforepresenting acutely with long bone fractures,patientswith malignancies metastaticto
bone may present with constitutional symptoms common to many cancers, or with
symptomatologyspecifictothegivenprimarycancer.Patientswithmalignanciesmetastaticto
thelongbonesofthelowerextremitiesmayalsonotethighpain,forelegpain,orpaininoneor
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more joints. Additionally, some patients may exhibit signs and symptoms of hypercalcemia
secondarytoosteoclastactivity.
Tests
Radiologictestscanoftenreveal irregularitiesconsistentwith metastatic disease inpatients
whosuffer pathologicfractures,typicallydemonstrating a fracture linethrough theabnormal
bone. Often noted is cortical thinning, endosteal reabsorption, and cystic-appearing lytic
lesions. Plain films will often suffice to reveal the pathologic fracture, whereas advanced
imaging,suchascomputedtomography(CT)ormagneticresonanceimaging(MRI),canserve
toprovideadditionaldetailsusefulinplanningfracturefixation(Fig.19-2).
Radiographic imaging may also suggest to the examiner which or what type ofprimary
malignancy may underlie a pathologic fracture, although a definitive diagnosis requires
examinationoftheaffectedtissueunderamicroscope.Assessingfortheprimarymalignancyin
patientswithpathologic bonefracturesofteninvolveslaboratorytestingaimedatmeasuring
thebiomarkersofspecificmalignantdiseases,andotherscreeningtests.
Severalprimarycancersarecommonlyassociatedwithbonymetastases,withcancersof
the breast,prostate,andlungcomprisingover80%ofthe malignanciesmetastatictobone.
13
Abnormal screening testsforanyof these cancers inpatientswhohave suffered pathologic
longbonefracturescanleadtoapresumptivecancerdiagnosis.Examplesofsuchtestsinclude
prostate-specific antigen levelstoscreenforprostatecancer,mammographyorultrasoundto
screenforbreastcancer,low-doseCTscanningtoscreenforlungcancer,andurinecytologyto
screenforkidneycancer.
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FIGURE19-2.Apathologicfemurfractureinapatientwithlungcancermetastatictobone.(EisenbergRL.AnAtlas
ofDifferentialDiagnosis.4thed.Philadelphia,PA:LippincottWilliams&Wilkins;2003,withpermission.)
TreatmentsandTherapies
Initially, the patient should be assessed for neurovascular compromise, and orthopedic
consultationshouldbeobtainedimmediately.Paincontrol andreductionandsplintingofthe
affected extremity should be performed in a timely fashion. The definitive treatment of
pathologic lower extremity long bone fractures is primarily orthopedic, focused on open
reductionandinternalfracturefixationusingorthopedichardware.
Thegeneraltreatmentofbonymetastasesmayincluderadiationtherapyand/orradioactive
injectiontherapytodestroycancercells,bisphosphonatetherapytodecreasetherateofbone
reabsorption,andtumorablativetherapies.
14
Treatment of the primary malignancy is often considered on a case-by-case basis, as
pathologicfractures occurring secondaryto malignant disease that hasmetastasizedtobone
are,bydefinition,associatedwithatumorthathasspreadbeyonditssiteoforigin.Removalof
a primary tumorthat hasalreadymetastasizeddoes not rid the bodyofcancer, andis often
undertaken only for palliative reasons. The approach to treatment of the primary cancer in
patients with pathologic fractures is therefore practically identical to the treatment of
metastaticdiseasewithoutfracture.
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ACUTELOWEREXTREMITYJOINTPAINAND
SWELLINGASAMANIFESTATIONOFLYMEDISEASE
Lyme disease, also knownasborreliosis, is causedby bloodstream infection with Borrelia
burgdorferi, a bacterium that infects mice and other mammals, and is often carried in the
salivaryglandsofblack-leggedticksoftheIxodesgenus.15IntheUnitedStates,I. scapularis
and I. pacificus species serve as a vector of transmission to humans. Ticks acquire the
infectionwhilefeedingoninfectedanimals,andthentransmittheinfectiontohumansandother
animalsduringsubsequentfeedings.
Patientswhofind atickattachedmaytakestepstoremovethetick,andmayalsotake a
prophylacticantibioticdosetopreventLymedisease.Thosewhonevernoticetheattachedtick
maybeunawareofthepossibleexposuretoB.burgdorferi,andmaythereforeneverpresentto
initiateearlytreatment.Shouldpatientsmissorfailtorecognizeearlysymptoms,suchasthe
hallmarkerythema migransrashor theless specific influenza-likeillness, they mayinstead
presentlaterwithcomplaintsrelatedtodisseminatedinfection,includingpaininoneormore
joints.
Lymearthritisistypicallycharacterizedasanintermittentoligoarticulararthritisprimarily
affectinglargejoints.Thekneesarethemostcommonlyinvolvedjoints;painfulswellingand
decreased rangeof motionis often seen.Although initial arthritis symptoms maybe dueto
activebacterialinfection,chronicarthritissymptomsmaybethesequelaeofaninflammatory
reactiontothecausativebacteriainLymedisease,causingdamagetothecartilageliningjoint
articularsurfaces;repeatedcyclesofinflammationmighttriggerprogressiveirreversiblejoint
destructionthatremainsbeyondtheeradicationofthebacterialinfection.
16
Presentation
PatientsmaypresentintheearlystagesofLymediseaseinfectionwithvaguecomplaints;only
somewillnotetheclassicerythemamigransrash,describedasaringoferythemawithcentral
clearing.PatientsmaypresentinlaterstagesofLymediseasewithdiffusemyalgias,symptoms
ofBellpalsy,meningitis,atrioventricularconductiondisturbance,andjointpains.Amultitude
ofothersymptomsmaybeseeninpatientswithLymedisease,manyofwhicharenonspecific
andfound in association with other illnesses. Often,making thediagnosis ofLyme disease
requiresafairlyhighindexofsuspicion.
SignsandSymptoms
Cliniciansmayrecognizetheclassicerythemamigransrash,ormayelicitahistoryofpotential
tickexposureinpatientswithconstitutionalsymptomspresentinginthe earlystagesofLyme
disease infection. Practitioners in endemic areas may consider potential Lyme disease in
nearly all patients with vague symptoms, whereas caregivers in areas where disease
prevalenceislowmayfailtoconsiderthepossibilityofLymediseaseearlyenough.Signsand
symptoms of early Lyme disease may overlap those of viral syndromes, and canbe easily
missedoroverlooked.
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Nearly two-thirds of untreated patients will develop arthralgias, signaling progression
from the first stage of Lyme disease to the second or third stage. Patients with early
disseminatedborreliosismaydevelopintermittentpolyarticulararthritisaffectingseverallarge
joints, typically progressing to monoarticular joint pain, most commonly affecting the knee
joints.
17
Tests
TheCentersforDiseaseControlandPrevention(CDC)recommendsatwo-stepapproachto
testing for thepresence of Lyme disease, based on the idea that immunocompetent patients
exposed to B. burgdorferi will subsequently develop antibodies to counter the infection,
whereas patients not previouslyexposedwill notcarrythesespecific antibodies18(see Fig.
19-1).Enzyme-linkedimmunosorbentassay(ELISA)testsareconsideredreliableinexcluding
diseaseexposurewhennegative,butrequireconfirmationwhenpositive.PositiveELISAtests
arefollowedbyWesternblotanalysis,toensurethattheantibodiesfoundthroughELISAare
trulydirectedagainstB.burgdorferibacteria.
Polymerasechainreaction(PCR)canalsobeusedtodetectinfectionwithB.burgdorferi,
by replicating and amplifying bacterial DNA present in synovial and cerebrospinal fluid.
However,PCRiserrorprone,andconsideredlessreliablethanserologyforthedetectionof
B.burgdorferi bacteria. PCRis not recommended bythe CDCor cleared bythe Foodand
DrugAdministration19fortheroutinetestingofpotentialLymediseasepatients.
TreatmentsandTherapies
AntibioticsarethemainstayofprophylaxisagainstandtreatmentofLymedisease.Prophylaxis
againstLymedisease seroconversioninadultpatients,andinchildrenaged8yearsorolder
weighingover50kg,whoreportremovalofattachedtickswithinthepast72hours, canbe
accomplishedthroughtheadministration ofasingle200mgdoseofdoxycycline.Guidelines
publishedbytheInfectiousDiseasesSocietyofAmericaalsoprovidetreatmentregimensfor
bothearlyandlaterstageLymedisease.
20
Symptomatic treatment of patients with negative PCR analysis of synovial fluid after
appropriate antibiotic therapy noting persistent arthritis symptoms includes NSAIDs, intraarticularcorticosteroidinjections,andDMARDs.Inrefractorycasesthatfailtoimprovewith
the above measures, surgical synovectomy for amelioration of symptoms maybe necessary
(Fig.19-3).
21
ACUTECALFPAINANDSWELLINGSECONDARYTO
DEEPVENOUSTHROMBOSISASAMANIFESTATION
OFHYPERCOAGULABLEDISEASESTATES
Hypercoagulability describes an increased propensity to form clots within the circulatory
system. Also known as thrombophilia, several genetic conditions are associated with the
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prothrombotic state that defines hypercoagulability; numerous acquired risk factors for
developingclotsinthebloodstreamhavealsobeenidentified.Whethercongenitaloracquired,
many hypercoagulable patients remain unaware of an increased risk of clot formation until
afterreceivinganunexpectedrelateddiagnosis.
FIGURE19-3.CDCrecommendedapproachtotestingforsuspectedLymedisease.(Obtainedfrom
http://www.cdc.gov/lyme/resources/twotieredtesting.pdf.AccessedJanuary17,2017.)
Although hypercoagulable disease states can increase the riskofthrombosis in both the
arterial and venous circulatory subsystems, presenting symptoms may differ sufficiently to
allow the clinician to surmise whether an arterial or venous thrombosis is the more likely
causeofapatient’spresentation.Patientswithlowerextremitydeepvenousthrombosis(DVT)
will typically present with unilateral calf pain and swelling,22 although symptoms may be
minimal or absent. Patients may also note localized erythema andwarmththat may appear
clinicallysimilartocellulitisoftheforeleg.
PatientswithDVTofthelowerextremityareatriskforembolizationoftheclotintothe
lungs.23Morespecifically,thethrombusmaymobilizefromthedeepveinsoftheleg,traveling
withdeoxygenatedbloodthroughtherightsideoftheheartintothepulmonaryarteries.Avery
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largepulmonaryembolus(PE)thatstraddlestherightandleftpulmonaryarteriesistermeda
saddle embolus, andmayprove rapidly fatal ifitcompletelyimpedes blood flow from the
venous collecting system intothelungs, eliminatingoxygen transferand flow of oxygenated
bloodtothetissues.
DVT should be considered in patients presenting with complaints of calf pain and
swelling, particularly if the patient is known to have a disease associated with
hypercoagulability or to have one or more prothrombotic risk factors. A high index of
suspicionwhenevaluatingpatientswiththesesymptomsmaydecreasetheriskofmissingthe
diagnosis.
Presentation
Patients with lower extremity DVT maypresentwith any combination of calfpain,foreleg
swelling, lower extremityerythema, and warmth, and theappearance of theaffected lower
extremitymaycloselyresemblecellulitis(Fig.19-4).
Patients with these complaints are at increased risk of pulmonary embolism, and may
report additional symptomatology such as chest pain, dyspnea, or hemoptysis. Although
patientswithPEmayreporttheseorseveralothersymptoms,itisimportanttonotethatsome
patients may remain asymptomatic, and clinicians must always consider the risk of silent
embolization.
SignsandSymptoms
Patientsmaynoteanycombinationofcalfpain,lowerextremityswelling,localizederythema,
andwarmth,ormaylacksymptomsaltogether.Thephysicalexamaloneisusuallyinsufficient
foreitherconfirmingorexcludingadiagnosisofDVT,althoughcliniciansmaynotecalfpain
on dorsiflexionofthe foot,knownasapositive Homansign, inpatientsultimatelyfound to
have a DVT. Nevertheless, although many potential causes of lower extremity pain and
swellingareknowntoexist,DVTshouldalwaysbeconsideredinpatientspresentingwithcalf
painandswelling.
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FIGURE19-4.Postthromboticlegulcer.Thisphotographfroma50-year-oldmanwithahistoryofDVT2years
beforedemonstratesbrownishhyperpigmentationofalargeregionofskinalongtheleftcalf.Thereisasmallround
ulcerwithinacentralareaoferythemaandinflammation.Theankleregion,andespeciallyitsmedialaspect,isthe
mostcommonsiteofvenouslegulcers,buttheycanalsooccurinthemiddleandlowercalf,asdepictedinthe
image.(FromGeschwindJ,DakeM.Abrams’Angiography.Philadelphia,PA:WoltersKluwer;2014,with
permission.)
Tests
Ultrasonography is useful for detecting lower extremity DVT, and relies on identifying
noncompressible portions ofthevenous anatomy.Ultrasound islimited inthatitis operator
dependent and is subject to error. A venogram also allows visualization of the venous
circulationofthelower extremity,usingradiographicimagingtodetectflow ofdyeinjected
intothebloodstream.
SomecliniciansuseD-dimerassaysthatdetectfibrindegradationproductsproducedwhen
clotsareformed.UsedincombinationwithaclinicaldecisiontoolknownasTheWellsscore,
theseassaysmayserve toidentify thosepatientswhocansafelyforegoDopplerimagingto
reliablyexcludeDVT.
Lowersensitivityqualitativeassayscansafelyexcludeclotformationinpatientsdeemed
low risk by Wells score criteria, whereas higher sensitivity quantitative assays, with 98%
sensitivityanda highnegativepredictivevalue,canexcludeDVTinbothlow andmoderate
riskpatients.24BothqualitativeandquantitativeD-dimerassaysare consideredunreliable in
excludingclotformationinpatientswhoareconsideredtobeathighriskofDVT,andshould
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Table19-1.
notbeusedinplaceofimagingstudiesinthesepatients(Table19-1).
WellsScoreCriteriaforPredictingtheProbabilityofDVT
WellsScoreEstimatesProbabilityofDVT
TheelementsoftheWellsscoreshouldbeascertainedintheusualevaluationofapatientwithsuspectedDVT.
1PointEachFor:
Activecancer
Paralysis,paresis,recentplasterimmobilizationoflowerlimb
Recentlybedriddenfor>3dormajorsurgeryinpast4wk
Localizedtendernessalongdistributionofdeepvenoussystem
Entirelegswollen
Calfswelling>3cmcomparedtoasymptomaticleg
Pittingedema
Collateralsuperficialveins
−2PointsFor:
AlternativediagnosisaslikelyormorelikelythanthatofDVT
Probability:
High >3points
Intermediate 1or2points
Low <0points
Obtainedfromhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3183832/.AccessedJanuary17,2017.
TreatmentsandTherapies
Thetreatment oflowerextremityDVTis directedagainstextension andembolizationofthe
clot. The mainstay of therapyis treatmentwithanticoagulants,designed to shift the balance
betweenclotformationandclotdissolutionfromtheformertothelatter.Medicationsthatshift
thisbalancealsoincreasetheriskofunintendedbleeding,whichmustbeweighedonacaseby-casebasisinpatientswithconsiderable bleeding risk,suchasthose whofallandinjure
themselvesfrequently.
Inpatientswhocannotbeadequatelyanticoagulated,becauseoffallriskorotherreason,
filtersmaybeplacedintheinferiorvenacavatodecreasetheembolizationrisk.Thesefilters
are designed to trap larger clots that form in the lower extremities, serving as a physical
barrier.Smallerclotsmayslippastthespokesofthefilterhowever,andserveasanidusfor
largerclotformation.In somecases,inferiorvenacavafiltersareusedincombinationwith
anticoagulationtofurtherdecreaseembolismrisk.
Patientswith newly diagnosed unexplained DVT will require acomplete evaluation for
hypercoagulable disorders, including testing for Protein C and Protein S deficiencies, the
presence ofFactorV Leiden,elevatedhomocysteineor fibrinogenlevels, a mutation ofthe
prothrombingene,oroneofseveralothercongenitallyacquiredhypercoagulabilitydisorders.
Expeditiousfollow-upwith theprimaryphysicianandpromptreferraltoa hematologistare
recommended.
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ACUTEANKLEANDFOOTDEFORMITIESSECONDARY
TOCHARCOTARTHROPATHYASAMANIFESTATION
OFDIABETICNEUROPATHY
Diabetes mellitus is a complex systemic disease process, with a multitude of potential
manifestationsandlong-termsequelae,includingdiabeticneuropathies.Groupedbroadlyinto
autonomic,proximal, focal,and peripheralneuropathies,25diabeticneuropathies cancausea
range of inappropriate symptoms, including autonomic dysfunction, muscle weakness, and
paresthesias.
Diabeticpatientswhodevelopperipheralneuropathiesmaynoteparesthesiasaffectingthe
extremities,withthelowerextremitiestypicallyaffectedbeforetheupperextremities.These
paresthesias may be characterized by pain, tingling, hypersensitivity to light touch, burning
discomfort,and possiblydecreased or altogetherabsent sensationto external stimuli. When
patients lose the ability to appropriately sense painful or noxious stimuli, they may suffer
injuries, yet remain unaware. The injuries suffered may be acute, such as immersion burn
injuries, or indolent, such as progressive cellulitis secondary to skin abrasion or puncture
injuries.Patientsmayfailtorecognizetheseinjuriesuntilsecondarysymptomsarenoted,as
painiseitherunappreciatedorunderappreciated.
Charcot arthropathy is a disease process whereby joint structures are progressively
destroyedthrough repetitive injuryoccurring in the face ofcompromised sensation,suchas
those occurring in relation to the sensorimotor compromise noted with diabetic peripheral
neuropathy.Inthelowerextremities,theterm“Charcotfoot”describesdestructionofthejoints
oftheankleandfoot,wherefractures,dislocations,andlossofstructuralintegritycanbeseen
inpatientswholacktheability to feel pain,and who thusfail tomodify or eliminatetheir
exposuretotherepetitiveinjuries,allowingdamagetoprogressoraccumulate.Althoughmany
diseaseprocessesareassociatedwithperipheralneuropathies,andthusmaybeconsideredto
bepotentialprecipitantsofaCharcotarthropathy,diabetesiswidelyconsideredtobeoneof
themorecommoncausesofperipheralneuropathyandthemostcommonetiologyofCharcot
arthropathy.
26
Presentation
Diabetic patients withCharcotarthropathy affecting the lower extremities maypresent with
complaintsofatraumaticankleorfootpain,orinstead withpainless swelling, redness,and
warmth,mimickinganinfectiousprocess.Patientsmayalsonotelimitedabilitytobearweight,
because of bony destruction leading to joint deformities and structural instability. Joint
destructionmayprogresswithcontinuedattemptedambulation,asthepatientfailstorecognize
additionalmicrotraumaormicrofractures,furthercompromisingjointstability.
SignsandSymptoms
DuringtheinitialdestructivephaseofCharcotneuropathicjointdestruction,patientsmaynote
painfulorpainless swelling,redness,warmth,or trouble ambulating.During the subsequent
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