ILADS LD Conference 2012 Boston: Andrea Gaito, MD - Lyme Arthritis

ILADS Lyme Disease Conference 2012 Boston Notes

Clinical Evaluation and Treatment of Lyme Arthritis - An Autoimmune Perspective - Andrea Gaito, MD

This lecture was completely geared for doctors to help them differentiate between Arthritis and Lyme Disease in the diagnosis process.

However, it was a fascinating presentation and I learned so much from Dr. Gaito. This would be helpful information to take with you to your doctor, even if you already see an LLMD - if you are having joint pain and you haven't been tested for Lyme Arthritis, this information is important!

This can help determine if you need IV antibiotics or if going with orals or a natural route is possible.

This is long, but a lot of valuable information. I did my best to put it into an organized format.

Lyme Arthritis (LA)


- Occurs in 60% of untreated Lyme Disease (LD) and can start 2 weeks to 2 years into Lyme Disease infection

- 20% of children with Lyme Arthritis are actually missed

- LA can be one joint, 1-3 joints (most common in children), or many joints

- Bb rapidly disseminates to joints by inducing cytokines that induce vascular permeability

        > Causes swelling, inflammation

        >Autoimmune reaction

- The persistence of the organism stimulates both an inflammatory and an autoimmune response

- Three things happening with LA

        > Infection itself (Lyme)

        >Secondary manifestations of inflammation that can be extreme

        >Autoimmune reaction - where the body is actually attacking itself

- Persistence of Lyme drives the inflammation and autoimmunity

- Treatment controversies come up here

        >If still having LA pain - you need to keep treating

                 * In very few disorders does the autoimmune reaction and inflammation persist
                    unless the actual antigens of the bacteria are there

Diagnostic Evaluation - Patient History

- Complete Patient History

        >Tick exposure

                 * Your Backyard Bites - Article (I can't find it online)

        >  Sports injuries

                 * More vulnerable to getting LA in those joints

        > Osteoarthritis (OA), back problems

        > Osgood-Schlatter

                 *Very common in Boys and can cause LD to be missed

        >Chondromalacia Patella

                 *Very common in Girls - when knee cap rides a little high

        > Family history

                 *More vulnerable to Lyme Arthritis if any Autoimmune Disorders run in family

        >Medication history

                  *Antibiotics
                          ~If patient has taken any antibiotics in the last 6 months Lyme Disease
                    results can be skewed

                 *Anti-inflammatories
                           ~ANA tests can be off

 Diagnostic Evaluation - Physical Exam (PE)

        > The Physical Exam is the most important thing

                 * Must be a full exam, disrobed

        >  All joints must be examined and moved

        > Spine

                 *Alignment

                 *  Scoliosis

                                   ~ Patient may limp

                 *  Kyphosis

        > Joints - Range of motion

                 * Most important diagnostic criteria in peripheral joints exam

                 * Know standard values for each age group

        >Presence of Synovitis

                 *Differentiates Arthralgia from Arthritis, with or without joint effusion

                 *When the joint lining becomes thickened and inflamed

                 *The Hallmark of Lyme and Arthritis

                 *Presence of Synovitis on your PE is the differentiating factor between
                    Arthritis and Arthralgia

                                   ~Arthritis is when there is a physical change in the joint. Common
                                       in Late Stage and Chronic Lyme

                                   ~Arthralgia is just that the joint hurts but is structurally normal

        > Head and Neck

                 * Hair Loss

                 * Oral Ulcers

                                    ~ Part of low immune state of body

                 * Conjunctival Infection

                                   ~ Inflammatino

                 * Cranial nerve abnormalities

                                   ~ Bell's Palsy

                                   ~ Usually sensory components before Bell's Palsy: speech changes,
                                       taste changes, blurry vision

                 *Oral Thrush

                 *Enlarged Thyroid

                                   ~Fatigue in LD can be due to Secondary Thyroid problems associated
                                        with Lyme

                 * Submandibular Lymph Nodes (other Lymph nodes, as well)

        > Skin

                 * Vitiligo

                 * Hyperpigmentation

                 * Fibrosis

                 * Rashes

                 *Raynaud's Stigmata

                 * Spider angiomas

                 * Mottling

                 *Striae
                                    ~ Common in Bartonella

        > General Findings

                 * Dysrhythmias

                                    ~ Lyme, as opposed to RA, can cause many different problems with
                                        rhythm manifestations

                 * Hepatomegaly

                 * Splenomegaly

                 * Lympadenopathy

                 * Hypereflexia

                                    ~ Neurological signs

                                    ~ RA patients rarely have changes to their reflexes

        > Gait Evaluation - make the patient walk

                 * Limping

                 * Ataxia

                 * Disequilibrium

                 * Ataxia and Disequilibrium are more neurological and common with Neuro Lyme,
                     not an Autoimmune patient

Basic Lab Tests - Lyme Related

        > Western Blot

        > PCR

        > C6 Peptide

        > Co-infections

        > Viruses

                 * Parvo, Hepatitis

        > Bacterial Diseases

                 * Staph, Strep, Proteus, Mycoplasma

                 * Bacterial Diseases are commonly seen in Lyme

Basic Lab Tests - Basic Autoimmune Disease Labs

         > ANA (with titer)

                 *A low value: 1-40 positive ANA is not a big deal

                 *Pattern of ANA is more helpful than the number

                 *Order the Pattern NOT the Number

                 *Lyme stimulates ANA so can be used to follow recovery

        > Sedimentation Rate

                 *If Dr. Gaito could pick one test, this would be it

                 *Elderly people normally tend to have a sed-rate of 30-40

                 *Sed-rate is significant at 50-80

        > RF (with titer)

        > CPK

                 *Very important to have tested

                 *Myocitis is very common in Lyme Disease

                 *Always check in children with Lyme Disease

                        ~ Myocitis in children from any other disorder (except Polymyocitis)
                                        almost never happens except in Lyme Disease

                 *Very unused helpful test

        > CRP - same as Sedimentation Rate

        > Anti-dsDNA

                 *Extremely sensitive for Lupus

                 *If worried patient has LD and Lupus - do this test

        > Anti-CCP antibody

                 *This is a test for Early RA

                 *Poor prognostic value for RA

                 *Rarely is positive with Lyme Disease

                 *Rarely elevated in an infectious process except TB

                 *If it is around 250 you have a patient with just RA or a patient
                     who's Lyme has caused RA

        > Anti-RNP ab

        > Anti-Smith ab

        > SSA, SSB ab

                 *Does see a lot with Lyme

        > Anticardiolipin ab, IgM, IgG, IgA

                 *Very important with Lyme Disease Patients

                 *Lyme and Co-infections can trigger a hypo-coagulate state

                 *Very important to test any patient with Lyme before doing IV to prevent
                    problems (clotting)

        > IL-6

        > Tissue transglutaminase ab

                 *Celiac, Gluten senstivity, and the Colitis's

                 *Important to know because these patients have hardest time taking oral
                    antibiotics due to GI sensitivity


Vectra Panel - New Panel available in the USA

         >Very specific for RA

                 * So for patient that you can't tell if it is RA or Lyme (or RA caused by Lyme)

                 * Very cost effective for looking at markers more specific to RA

         > Panel:

                 *VCAM-1 vascular cell adhesion molecule-1
                 * EGF epidermal growth factor
                 *VEGF Vascular endothelial growth FactorA
                 *TNF-R1 Tumor necrosis factor recpror1
                 *YKL-40 matric metalloproteinase-1
                 *MMP-3
                 *Leptin
                 *  Resistin
                 * SAA serum amyloid A

Other Tests: X-Rays

         > Wonderful diagnostic tool and is extremely cost effective

         > Only do 1-2 joints

         > Look at bones

         > Look for soft tissue swelling

         > Joint space narrowing is the Hallmark for Osteoarthritis (OA)

                 *Never see it in anything but OA

                 *But remember - Ticks can bite people with OA!

                 *So don't let it be your diagnostic end point

                 *Lyme can stimulate a vigorous response in OA patients

         > Sclerosis often seen in patients with RA

         > Erosion can be seen in RA and LD

         > Dr. Gaito showed a "classic" Lyme X-Ray of a knee joint

                 *Bones look good

                 *Common in LD: fluid in the supra patella area

                 *LD rarely has fluid in the sub patella area

         > Septic Arthritis

                 *Requires surgical drainage even if caused by Lyme

                 *Large erosions in bone

Other Tests: MRI

          >If you can do it, not always possible due to cost

         > Highly effective in differentiating from Septic Arthritis or structural damage

         > Can distinguish:

                 *Joint effusions

                 *Synovial Thickness

                 *Marrow Edema

                        ~ Hallmark of Osteomyolitis NOT Lyme Disease

                 *Muscle Edema

                        ~ Often seen in Lyme Disease

                 *Meniscal Tears

                        ~ Often seen in Lyme Disease

         >  Three features highly suggestive of Lyme Disaese

                 *Myositis

                 *Adenopathy

                        ~ Specifically in the popliteal space

                 *Lack of subcutaneous edema

                        ~ Subcutaneous edema is classic in Septic Arthritis

Other Tests: Synovial Fluid Analysis

         > Very useful test

         > Use an 18 gauge needle

         > Normal joint fluid
                 *Amber colored
                 *Thick viscosity
                 *Clear
                 *WBC is < 2,000
                 *Mononuclear cells

         > Lyme Disease Arthritis fluid
                 *Yellow
                 *Thin viscosity
                 *Turbid
                 *WBC between 5,000 - 50,000
                 *Leukocytes

         > Order Lyme C6 Peptide, ELISA, WB, PCR with fluid

Treatment of Lyme Arthritis

         > Very important to treat Lyme Arthritis with IV Antibiotics

                 *Permanent damage can occur, and treatment will not be successful

         > IV Rocephin

                 *2 grams daily until resolution of the effusion

         > NSAIDS for pain

                 *Topical Voltaren Gel

         > Avoid steroids

         > Physical Therapy is important

                 *Especially for Shoulders, Hips, and Hand joints

         > Plaquenil

                 *Very important for LA treatment and LD treatment in general

                 *Accumulates in the lysosomes

                 *Helps de-stimulate the immune reaction and relieve inflammation

                 *Toll-like receptors (TLR) - proteins that hep facilitate the binding
                    and recognition of the proteins in Lyme bacteria

Treatment of Lyme with Arthralgia

         > Different than treatment of LA

         > Oral antibiotics are okay

         >Treat fully until patient is asymptomatic

         > Treat co-infections simultaneously

         >  Plaquenil

Common Rheumatoid Diseases with Lyme Disease

         > Rheumatoid Arthritis
                 *There are 7 criteria for RA - need 4 out of 7 for diagnosis

         > Systemic Lupus Erythematosus
                 *Very common Lyme Disease overlap

         > Polymyositis and Dermatomyositis
                 *More in pediatric Lyme population

         >Statin Educed Myocitis
                 *Patients on Lipitor, Crestor

                 *Muscle Weakness

         > Polymyalgia Rheumatica
                 *Inflammatory condition
                 *Stiffness

         > Antiphospholipid Antibody Disorders
                 *Hypo-coagulate States

         > Celiac Disease

         > Crohns Disease and Ulcerative Colitis

Autoimmunity in Lyme Disease

         >  In addition to the inflammatory response, the persistence of the Lyme bacteria can induce an autoimmune response

         > The human lymphocyte function antigen (hlFA1 alpha) contains a peptide with homology to OSPA 165-173 (part of Lyme Vaccine)

                *This is called a Shared epitope - so the body tries to fight that and ends up
                     fighting itself

                *Kicks in autoimmunity

         > Autoantibodies are produced as a secondary process which further promotes a variety of systemic responses

         >Inflammation ensues
                * There are Lipoproteins not Lipopoly saccharides on the spirochete that are
                    very potent inducers of inflammation

The Inflammatory Response in Lyme Disease

         >Spirochetal lipoproteins inducers of many pro and anti-inflammatory cytokines: TNF alpha & IL-6, IL-10, G-CSF, GMCSF

         >TNF alpha & IL-6 then stimulate T and B cell production
                * Causes further tissue destruction

         > Pathophysiology is most similar to RA not OA

         > The occurance of this phenomena correlates with the frequency of certain MHC classes, HLA DR, HLA DB, and Bb strain (BbRST1)
                * "Treatment resistant arthritis"

Treatment Options for patients who have Lyme WITH Rheumatoid Arthritis (not LA, but LD and RA)

         > NSAIDS

         > Plaquenil

         > Biologics

         > Methotrexate

         > Imuran

         > Steroids - only if absolutely necessary

Lyme Disease and Generalized AI Disorders

         > Lyme and SLE: Antibiotics + Plaquenil

         > Lyme and Sjogrens : Antibiotics + Plaquenil

         > Lyme and myositis: Antibiotics + Lowest dose steroids, cosider MTX as steroid sparing agent

         > Lyme and antiphospholipid disorders: Antibiotics + Aspirin or other anticoagulants as needed

Synovectomy

         > May be necessary if patient does not respond to treatement

         > May also contribute to diagnosis in seronegative patient

         > Success of synovectomy may be related to removal of antigenic material

         > Hard to get test done - need Ortho

         > Most literature is European, uncommonly done in the US