Rheumatologic Rheumatologic

Manifestations of LymeManifestations of Lyme

DiseaseDisease

Andrea Gaito, MDAndrea Gaito, MD

Lyme ArthritisLyme Arthritis

�� Lyme Arthritis occurs in 60% of patients Lyme Arthritis occurs in 60% of patients

with untreated Lyme diseasewith untreated Lyme disease

�� Can be a Can be a mono,oligomono,oligo or or polyarthritispolyarthritis

�� Bb rapidly disseminates to joints by inducing Bb rapidly disseminates to joints by inducing

cytokines that induce vascular permeabilitycytokines that induce vascular permeability

�� The persistence of the organism stimulates The persistence of the organism stimulates

both an inflammatory and an autoimmune both an inflammatory and an autoimmune

responseresponse

Case reportCase report

�� 18 year old white female presents with 2 18 year old white female presents with 2

month history of right knee pain, month history of right knee pain,

accompanied by fatigue and headache and accompanied by fatigue and headache and

blurry vision. No known tick bite or rash. blurry vision. No known tick bite or rash.

Seen by orthopedist, knee aspirated, fluid Seen by orthopedist, knee aspirated, fluid

not tested. not tested.

�� Labs: Lyme Elisa: positive 1.50, western Labs: Lyme Elisa: positive 1.50, western

blot:IgMblot:IgM +23,41 +23,41 IgGIgG 41, 41, RfRf: 15, ANA 1:40 : 15, ANA 1:40

�� SedSed rate: 32rate: 32

Diagnostic Evaluation Diagnostic Evaluation

�� History: tick exposure, sports History: tick exposure, sports injuries,structuralinjuries,structural issues: Osgood issues: Osgood SchlatterSchlatter, , chondromalaciachondromalacia

�� Family History: All autoimmune disorders, Family History: All autoimmune disorders, esp. RA, SLE, esp. RA, SLE, hypothyroidism,Crohns,UChypothyroidism,Crohns,UC

�� Medication History: Use of antibiotics, Medication History: Use of antibiotics, NSAIDSNSAIDS

Physical ExamPhysical Exam

�� Vital to perform a full physical exam on Vital to perform a full physical exam on every patient, disrobedevery patient, disrobed

�� Spine: alignment, Spine: alignment, scoliosis,kyphosisscoliosis,kyphosis

�� Range of Motion: most important diagnostic Range of Motion: most important diagnostic criteria in peripheral joints criteria in peripheral joints exam,knowexam,knowstandard values for age groupsstandard values for age groups

�� Presence of Presence of synovitissynovitis: differentiates : differentiates arthralgiaarthralgia from arthritis, with or without from arthritis, with or without joint effusion joint effusion

Physical Exam, Physical Exam,

(continued)(continued)

�� Head and Neck: hair loss, oral ulcerations, Head and Neck: hair loss, oral ulcerations, conjunctivalconjunctival injection, cranial nerve abnormalities, injection, cranial nerve abnormalities, oral thrush, enlarged thyroid, oral thrush, enlarged thyroid, submandibularsubmandibular lymph lymph nodesnodes

�� Skin: Skin: vitiligovitiligo, , hyperpigmentationhyperpigmentation, fibrosis, rashes, , fibrosis, rashes, RaynaudRaynaud’’ss stigmata, spider stigmata, spider angiomasangiomas, mottling, mottling

�� General: General: dysrhythmiasdysrhythmias, , hepatomegalyhepatomegaly, , splenomegalysplenomegaly, , lymphadenopathy,hypereflexialymphadenopathy,hypereflexia

�� Gait evaluation: limping, ataxia, Gait evaluation: limping, ataxia, dysequilibriumdysequilibrium

Laboratory EvaluationLaboratory Evaluation

�� Lyme tests: western blot Lyme tests: western blot IgMIgM, , IgGIgG, ,

C6peptide,PCRC6peptide,PCR

�� CoinfectionsCoinfections: : BartonellaBartonella IgM/IgG,PCRIgM/IgG,PCR

�� EhrlichiaEhrlichia chaffeenischaffeenis & & AnaplasmosisAnaplasmosis,,

�� Babesia,Rickettsia,TularemiaBabesia,Rickettsia,Tularemia

�� Viruses: Viruses: ParvoParvo, , Hepatitis,etcHepatitis,etc

Laboratory Tests, Laboratory Tests,

(continued)(continued)

�� ANA (with titer)ANA (with titer)

�� Sedimentation rateSedimentation rate

�� RF (with titer)RF (with titer)

�� CPKCPK

�� CRPCRP

�� AntiAnti--dsDNAdsDNA

�� AntiAnti--CCP antibodyCCP antibody

�� AntiAnti--RNP RNP abab

�� AntiAnti--Smith Smith abab

�� SSA, SSB SSA, SSB abab

�� AnticardiolipinAnticardiolipin abab, , IgM,IgG,IgAIgM,IgG,IgA

�� ILIL--66

�� Tissue Tissue transglutaminasetransglutaminaseabab

Radiographic EvaluationRadiographic Evaluation

�� XraysXrays::

�� soft tissue swellingsoft tissue swelling

�� joint space narrowing joint space narrowing

�� sclerosis sclerosis

�� erosionserosions

MRIMRI

�� Highly effective in differentiating Lyme Highly effective in differentiating Lyme

arthritis from septic arthritis or structural arthritis from septic arthritis or structural

damagedamage

�� Can distinguish joint effusions, synovial Can distinguish joint effusions, synovial

thickness, marrow and muscle edema, and thickness, marrow and muscle edema, and

meniscealmenisceal tears.tears.

�� 3 features highly suggestive of Lyme: 3 features highly suggestive of Lyme:

myositismyositis, , adenopathyadenopathy and lack of and lack of

subcutaneous edemasubcutaneous edema

Synovial Fluid AnalysisSynovial Fluid Analysis

Normal Joint FluidNormal Joint Fluid

�� Amber coloredAmber colored

�� Thick viscosityThick viscosity

�� ClearClear

�� WBC < 2,000WBC < 2,000

�� Mononuclear cellsMononuclear cells

Lyme ArthritisLyme Arthritis

Yellow colorYellow color

Thin viscosityThin viscosity

TurbidTurbid

WBC 5,000WBC 5,000--50,00050,000

LeukocytesLeukocytes

+ Lyme C6peptide, + Lyme C6peptide,

elisa,PCRelisa,PCR

Treatment of Lyme Treatment of Lyme

ArthritisArthritis

�� IV IV RocephinRocephin, 2 grams daily until , 2 grams daily until

resolution of the effusionresolution of the effusion

�� NSAIDS?NSAIDS?

�� Repeat joint aspiration? Repeat joint aspiration?

�� Steroids?Steroids?

�� Physical therapy?Physical therapy?

Treatment of Lyme Treatment of Lyme

disease with disease with arthralgiaarthralgia

�� Antibiotic choices: Antibiotic choices: DoxycyclineDoxycycline, , CeftinCeftin, ,

and and BiaxinBiaxin, most effective for joint , most effective for joint

symptomssymptoms

�� Treat Treat coinfectionscoinfections simultaneouslysimultaneously

�� Placquinil,NSAIDSPlacquinil,NSAIDS, etc., etc.

Common Rheumatologic Common Rheumatologic

Disorders Associated with Disorders Associated with

Lyme DiseaseLyme Disease�� Rheumatoid ArthritisRheumatoid Arthritis

�� Systemic Lupus Systemic Lupus ErythematosusErythematosus

�� PolymyositisPolymyositis and and DermatomyositisDermatomyositis

�� PolymyalgiaPolymyalgia RheumaticaRheumatica

�� AntiphospholipidAntiphospholipid antibody disordersantibody disorders

�� Celiac diseaseCeliac disease

�� CrohnsCrohns disease and ulcerative colitisdisease and ulcerative colitis

Autoimmunity in Lyme Autoimmunity in Lyme

DiseaseDisease

�� In addition to the inflammatory response, In addition to the inflammatory response,

the persistence of the Lyme bacteria can the persistence of the Lyme bacteria can

induce an autoimmune responseinduce an autoimmune response

�� The human lymphocyte function antigen The human lymphocyte function antigen

((hlFAhlFA 1 alpha) contains a peptide with 1 alpha) contains a peptide with

homolgyhomolgy to OSPA 165to OSPA 165--173,(Lyme vaccine)173,(Lyme vaccine)

�� AutoantibodiesAutoantibodies are produced as a secondary are produced as a secondary

process which further promotes a variety of process which further promotes a variety of

systemic responsessystemic responses

The Inflammatory The Inflammatory

ResponseResponse

�� SpirochetalSpirochetal lipoproteins are potent inducers lipoproteins are potent inducers of many of many proinflammatoryproinflammatory cytokines: TNF cytokines: TNF alpha & ILalpha & IL--6, 6,

�� TNF alpha & ILTNF alpha & IL--6 then stimulate T and B cell 6 then stimulate T and B cell production, which causes further tissue production, which causes further tissue destructiondestruction

�� PathophysiologyPathophysiology is most similar to is most similar to rheumatoid arthritis not osteoarthritisrheumatoid arthritis not osteoarthritis

�� The occurrence of this phenomena The occurrence of this phenomena correlates with the frequency of certain correlates with the frequency of certain MHC classes, HLA DR, HLA DBMHC classes, HLA DR, HLA DB

Management of Lyme Management of Lyme

Disease and Autoimmune Disease and Autoimmune

DisordersDisorders

Lyme Disease and Lyme Disease and

Rheumatoid ArthritisRheumatoid Arthritis

�� Treatments options:Treatments options:

�� NsaidsNsaids

�� PlacquinilPlacquinil

�� Biologics: Biologics: EnbrelEnbrel, , HumiraHumira, , Remicade,OrenciaRemicade,Orencia, , CimziaCimzia, etc., etc.

�� MethotrexateMethotrexate

�� ImuranImuran

�� steroidssteroids

Lyme Disease and Lyme Disease and

Generalized autoimmune Generalized autoimmune

disordersdisorders�� Lyme and SLE: antibiotics + Lyme and SLE: antibiotics + placquinilplacquinil

�� Lyme and Lyme and SjogrensSjogrens: antibiotics : antibiotics ++placquinilplacquinil

�� Lyme and Lyme and myositismyositis: antibiotics +lowest : antibiotics +lowest dose dose steroids,considersteroids,consider mtxmtx as steroid as steroid sparing agentsparing agent

�� Lyme and Lyme and antiphospholipidantiphospholipid disorders: disorders: antibiotics + aspirin, others as neededantibiotics + aspirin, others as needed

SynovectomySynovectomy

�� May be necessary if patient does not May be necessary if patient does not

respond to treatment.respond to treatment.

�� May also contribute to diagnosis in May also contribute to diagnosis in

seronegativeseronegative patientspatients

�� May temporize joint damage to avoid May temporize joint damage to avoid

replacement replacement

Case ReportsCase Reports

�� OsteoblasticOsteoblastic lesions secondary to ACAlesions secondary to ACA

�� BorrelialBorrelial LymphocytomaLymphocytoma

�� Nodular Nodular FascitisFascitis

�� WegnerWegner’’s s GranulomatosisGranulomatosis with AV with AV

blockblock

�� Lyme arthritis secondary to Lyme arthritis secondary to autologousautologous

chondrocytechondrocyte transplanationtransplanation

Lyme disease can manifest in a diverse Lyme disease can manifest in a diverse

array of inflammatory and autoimmune array of inflammatory and autoimmune

disorders. Most are triggered and driven disorders. Most are triggered and driven

by the persistence of bacterial proteins in by the persistence of bacterial proteins in

host tissue. The successful treatment of host tissue. The successful treatment of

the patient with Lyme disease involves the patient with Lyme disease involves

treating the primary infection as well as treating the primary infection as well as

identifying and treating the secondary identifying and treating the secondary

rheumatologic disorder if present.rheumatologic disorder if present.