Download Presentation of gout

Inflammation, Crystalline Disorders, and Knee
Surgery: oh, my!
22-29 CLINICAL MEDICINE
Pearls
Lecture 22 – Inflammatory Arthritis
Evaluating and treating acute gout
Presentation of gout:
Exquisitely painful monoarthritis, self-limited, 50% of attacks occur in 1st MTP, 90% of patients
experience podagra (meaning they get gout in their big toe)
Gout is most common in the big toe, followed by: ankle, knee, finger, elbow=wrist, other joints…
Gout is worsened by behavior, especially binge drinking (his example was weekend fraternity parties)
EtOH supersaturates blood, so blood is now able to hold more uric acid but as your liver begins
metabolizing EtOH, the uric acid begins crystalizing in joints…
If you are thirsty, your body is 2L behind where your body should be to be properly hydrated
Tophus: large, asymmetric deposit of uric acid crystals at a joint with gout (worse if lead poisoning)
Overview of the pathogenesis of gout: Vast majority of gout cases are due to under-excretion of uric
acid crystals
5 cardinal signs of inflammation:
Redness, warmth, swelling, pain and loss of function
Treatment Goals:
End acute attack promptly and safely
Prevent recurrent attacks
Prevent or reverse complications
Prevent formation of kidney stones
Treat associated conditions (obesity, hypertriglyceridemia, HTN, EtOH excess)
Treatment: NSAIDS, Corticosteroids (systemic; be careful with gouty diabetics here!), local joint
aspiration & injection, oral colchicine, IV Colchicine (BAD!), parental and suppository
Circumstances associated with gout attacks:
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Trauma, EtOH ingestion, dietary excess, surgery, acute diverticulitis and other febrile illnesses
*note: Diuretics decrease uric acid excretion
For chronic gout:
Treatment: Allopurinol (self-induced pharmacokinetics), which reduces the build-up of uric acid by
inhibiting xanthine oxidase: max dose is 800mg
Allopurinol is preferred if:
Urolithiasis
Secondary gout with myeloproliferative disorders (cell lysis syndrome prophylaxis)
Renal insufficiency (adjust dose!)
Tophaceous gout
HPRT deficiency or PP-ribose-P synthetase overactivity
Allergy to uricosurics
Note: Aspirin reverses effect of Probenecid
Indications for Drug Treatment of Hyperuricemia:
2-3 gout attacks, tophaceous gout, chronic arthritis with erosions, renal stones, and asymptomatic
hyperuricemia (12mg/dL serum uric acid level; 1100mg of uric acid excretion/24h)
Diagnosing acute gout
Lab Tests have caveats and limits
1. *CBC with WBC, hematocrit, platelets, red cell distributive width (takes 1hr for results)
Provides you with an understanding of your patient’s metabolic health status
2. BUN & creatinine (takes 1hr for results)
Provides you with an better understanding of which drugs your patient can handle
3. Arthroscopy
look at color, measure volume, do “string test”, look for RBC and WBC, and look at crystals
under microscopy
[Use Ethyl Chloride numbs surface/cutaneous nerves before injection]
4. Uric acid (takes 24hrs for results)
No uric acid draw for acute gout presentation, especially for “virgin” case (meaning new patient
to you/ first presentation of gout) b/c it could be falsely high or low, so do uric acid labs when
you do a follow-up in 2 weeks
Target goal for uric acid: <6mg/dL
Joint aspiration in gout
Normal Joint Synovial fluid: clear, should “string”- have characteristic thickness that allows it to stretch
without breaking
Gout Joint Synovial fluid: Gout crystals under polarized light appear: yellow, needle-shaped, negatively
birefringent
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“YUPA”= yellow, urate, parallel to the axis- negatively birefringent
Diagnosing rheumatoid arthritis
Similar presentation to gout but presents as polyarthritis involving at least 3 joints
+ rheumatoid factor or anti-CCP
Rheumatoid factor (RF) is an IgM antibody against the Fc portion of IgG and is present in ~70% of
RA cases in the 1st 6 months and is present in ~85% of RA cases in the 1st 2 years; can be present without
the patient having symptoms of RA (FALSE POSITIVES!). +RF test can be indicative of other diseases like
bacterial endocarditis, Hepatitis B or Hepatitis C, tuberculosis, syphilis, leprosy infections or pulmonary
diseases or cancer malignancy.
Elevated CRP or ESR
Exclusion of diseases with similar clinical features
Duration of these symptoms >6 weeks
Erosive disease with typical features of rheumatoid arthritis as above
Inactive arthritis but with above criteria
Lecture 23 – Hip and Back Pain (Morris Solis)
Most common chronic pain
Most common chronic pain is back pain with 80% of the population having back pain at some point in
their lives. ~8million Americans suffer new back injuries every year with and 400,000 of those suffer
disabling back injuries. Twice as many back injuries occurring at home as in the workplace. Can appear
as bimodal distribution for hip pain. Elderly: double the risk of chronic back pain with each decade after
age 50. Young: chronic back pain occurs with high energy (impact?) sports.
Risk factors for back pain: increased caffeine intake, increased alcohol intake, small body size, smoking
Common causes of hip/back pain:
Anterior:
Osteoarthritis/ RA/Fractures
Iliopsoas Syndrome
Meralgia Paresthetica
Posterior:
Piriformis Syndrome
Spondylolysis
Spondylolisthesis
Gluteal medius tendonitis
Lateral:
IT Band Syndrome
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Greater trochanteric bursitis
Meralgia paresthetica
Diagnose meralgia paresthetica
Painful mononeuropathy of the lateral femoral cutaneous nerve coming off femoral nerve and causing
sharp, stabbing, burning pain to radiate down the anterior and lateral thigh. Symptoms are ONLY
SENSORY, NO MOTOR LOSS.
Causes: 1. Seat Belt Injury (or tight tool belts, body armor or duty belts worn by police, military or
carpenters) where seat belt pulls the inguinal ligament, entrapping the lateral femoral cutaneous nerve
as it passes through the inguinal ligament
2. Patient with Diabetes mellitus with peripheral neuropathy that presents as meralgia
paresthetica. Symptoms should be reproduced with deep palpation below ASIS and tapping over
inguinal ligament; worse with standing or walking but improved with sitting.
3. Pregnant patient with a gravid uterus (meaning you can feel she’s pregnant when you do an
abdominal exam) that is pushing down on her inguinal ligament, which pushes on her lateral cutaneous
nerve meralgia paresthetica.
Common in: obese patients, middle-age patients, diabetics, unilaterally in runners
Treatments: anti-neuropathic drugs such as Lyrica or Gabapentin (both of these are oral); inject
corticosteroids using Ultrasound guidance
Lumbar facet arthropathy symptoms
Lumbar spine disease that is degenerative arthritis affecting the facet joints in the spine
Characteristically presents as lumbar pain that shoots UP the back OR wraps around hip and shoots into
the groin/thigh
Does not present below the knee
Diagnosis: Rotation with extension or extension itself reproduces the pain
Medications for neuropathy
NO OPOIDS!!
Anti-neuropathic medications: Gabapentin, Lyrica…
Non-steroidal anti-inflammatories
Trineurosol injection?
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Distinguish snapping hip / IT band / greater trochanteric bursitis
Patient presents with “hip pain”
Snapping hip Syndrome/Psoas Syndrome
Normal: Psoas muscle originates at transverse processes of L1-L4, joins with iliacus muscle at inguinal
ligament and inserts on lesser trochanter of femur, acting as the primary hip flexor.
Syndrome: tendon or bursa between tendon and hip joint become inflamed and irritated.
Common in: Dancers, gymnasts, track and field athletes
Presentation: Anterior groin pain with stiffness; sometimes you hear snapping, clicking when hip is in
flexion
Exam: tight hip flexors and can palpate “snap” when the iliopsoas tendon slides over the iliopectineal
eminence
IT Band Sydrome
Normal: IT band is thick, fascial band formed proximally by confluence of fascia from glut max, glut med,
tensor fascia latae, and vastus lateralis; band originates at lateral iliac crest and interts on lateral
tubercle of tibia.
Syndrome: inflammation along IT band due to overuse
Common in: Cyclists and Runners
Presentation: lateral thigh and knee pain that worsens when they strike the ground while running, +
Ober’s Test
Testing: Ober’s test: Dr abducts and extends affected hip from behind patient, then allows hip to drop to
exam table gently. If test produces pain, it’s positive.
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Greater trochanteric bursitis
Disease: trochanteric bursa inflammation, specifically in the lubricating sac located between the greater
trochanter and gluteus medius tendon/IT band **one of the most common causes of hip pain
Presentation: lateral hip pain with possible radiation down the ipsilateral thigh; pain worse when
moving hip or laying on affected side
Common in: runners or other physically active persons
Treatment: NSAID’s and injection
Lecture 24 – Osteoarthritis (Warren)
Aspiration of a joint with OA
Used to obtain synovial fluid to analyze for infection, crystals, blood cell counts, etc. or pull excess fluid
out to decrease swelling
For more info: google joint aspiration by American College of Rheumatology
Imaging for OA – findings on x-ray
a
c
b
Radiographs of the knee shows
(a) joint space narrowing in the medial compartment
(b) with subchondral sclerosis
(c) osteophytes
1st line treatments
Reduction of joint loading
Weight reduction
Decrease in stressful activities,
learning to work smarter,
Using devices to help, especially: crutches, canes, walkers, braces
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Exercise, Physical therapy
Strength exercises especially with exercise bands
aerobic activities like swimming
ROM activities to keep joints limber
agility exercises to maintain daily living skills
neck and back strength exercises to keep spine strong and limber
Drug Therapy
Acetaminophen (dose-dependent drug)
Tramadol
NSAID’s, such as ibuprofen, naproxen, or celecoxib (cause GI ulceration and renal compromise)
Opoids
*Glucosamine & Chondroitin, homeopathic and herbals are useless according to Dr. Warren
Intra-articular therapy
Corticosteroids or Hyaluronic acid injected distal to patella
Surgery
Most commonly affected joint
Gouty arthritis: 1st MTP joint
Osteoarthritis: weight-bearing joints: knees, hips, C-spine, L-spine, and feet: 1st MTP joint
Other important joints involved: fingers: DIP and PIP; hands: thumb base: CMC; gleno-humeral
*Joints that are spared: wrist, elbow & ankle
Lecture 25 – Rheumatologic Disorders in Children – Stewart
Treatment options for JIA
NSAID’s: only for non-severe disease
DMARD’s: Methotrexate* safest beyond NSAID’s, Biological TNF inhibitors (etanercept,
infliximab), and Clyclophosphamide, Axathioprine
Glucocorticoids: reserve for periods of severe disease or overwhelming inflammatory or
systemic illness
*Note: the child taking immunosuppressive drugs, such as DMARD’s, biologics, or steroids is considered
immunocompromised and should not receive live vaccines (such as MMR, Rotavirus, Varicella, Intranasal
influenza).
Differentiate septic v. RF v. JIA v. HSP
Septic arthritis: involves a single joint that is visibly red, swollen, warm and markedly tender
Presentation: fever, refusal to bear weight, elevated CRP and ESR
Testing: Arthrocentesis, Analysis of synovial fluid
*Urgent Diagnosis necessary to prevent complications
Reactive Arthritis/Reiter’s Disease/syndrome: joint involvement typically asymmetric peripheral
oligoarthritis of large joints (usually weight-bearing joints, like knees, hips, ankles, although shoulders,
wrists and elbows can be affected) as well as enthesitis, dactylitis, and inflammatory back pain. Extraarticular signs may or may not be present and are nonspecific: conjunctivitis or uveitis, constitutional
symptoms, nail changes, oral mucosal ulcers and balanitis.
Classic Triad: “you can’t see, you can’t pee, and you can’t climb a tree”
Conjunctivitis, urethritis, arthritis
Causes: follows an infection outside of the joint
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Enteric diarrhea
Causes: Salmonella, Shigella, Yersinia, Campylobacter jejuni, Giardia
Genitourinary Tract infections/ Urethritis
Causes: Chlamydia, Ureaplasma, N. gonorrhoeae, Reiter’s Syndrome
Presentation: onset of symptoms 1-4 weeks after initial infection
Lab findings: may or may not reveal initial organism
Elevated acute phase reactants
Inflammatory joint fluid without identifiable organism
Note: X-ray is not diagnostic
Treatment: address underlying infection, NSAID’s, supportive care
JIA: grouping of diseases that includes arthritis in at least 1 joint that persists for at least 6 weeks with an
age of onset younger than 16 Yo; most common rheumatic disease of children
Pathogenesis: Unknown: thought to be autoimmune or auto-inflammatory; presence of a dense
infiltration of mononuclear and plasma cells in the synovium
Increased cytokines (IL-6, IL-1, TNF) and inflammatory cells migrate into the synovial fluid, damaging
synovial tissue, cartilage and bone, causing abnormal bone mineralization and skeletal maturation that
is more prominent during pubertal growth spurts
Presentation:
Diagnostic Criteria: joint effusion OR 2 of the following criteria:
Stress pain
Limited ROM
Warmth
Erythema
Types of JIA:
1. Systemic JIA
Epidemiology: Peak age 2-4Yo; more common in girls than boys
Presentation: Daily fevers for at least 2 weeks accompanied by rash (faint, erythematous, salmoncolored, macular rash with discrete border) on the trunk and proximal extremities as well as visceral
involvement, particulary hepatospenomegaly, lymphadenopathy and serositis (pericarditis, myocarditis,
and pleuritis)
Lab findings: Negative RF, ANA rarely positive, high levels of ferritin, anemia of chronic disease, elevated
inflammatory markers (e.g. thrombocytosis >1million), and occasional leukemoid reaction
Prognosis: most difficult to control of the 3 types; 50% of arthritis cases remit within 1 year
Complications: severe destructive joint disease, growth abnormalities (leg length discrepancy),
macrophage activation syndrome (rare, fatal, involves persistent high fever, pancytopenia, low ESR,
abnormal liver function, encephalopathy, and disseminated intravascular coagulation)
2. Pauciarticular JIA
Epidemiology: 1-5 Yo; more common in girls than boys (4:1)
Presentation: <5 joints affected; knee and ankle most commonly affected, followed by elbows and wrists
Aysmptomatic uveitis in 30% of cases, causing characteristic yellow cataracts
Lab findings: nonspecific; 70% have positive ANA, which predicts a higher risk of developing uveitis
Types of Parciarticular JIA:
Persistent: involves 4 or fewer joints for at least 6 mo.
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Extended: extends to involve 5 or more joints after the 1st 6 mo.
3. Polyarticular
Epidemiology: bimodal: 1-3 Yo AND adolescents; more common in girls than boys
Presentation: Involves 5 or more joints in the 1st 6 mo., generally C spine, hips, shoulders,
tempomandibular joints; often accompanied by fatigue, fever, rheumatoid nodules
Types:
RF positive: most common presentation: symmetric in early adolescent girls with a high risk of severe
erosive joint disease and poorer functional outcomes
RF negative: fewer joints involved with 10% being destructive joint disease
Enthesitis-related Arthritis: arthritis accompanied by enthesitis/inflammation of tendon/ligament
insertion points OR arthritis PLUS 2 of the following criteria:
1. Sacroiliac joint tenderness OR inflammatory spinal pain
2. + HLA B27
3. + FH of uveitis with pain, IBD, or HLA B27 disease
4. Anterior uveitis with pain, erythema, or photophobia
Children may develop: Acute anterior uveitis, spondyloarthropathies (juvenile ankylosing spondylitis,
juvenile psoriatic arthritis, reactive arthritis or inflammatory bowel disease associated arthritis)
Epidemiology: 9-12Yo; more common in BOYS than girls (9:1)
Presentation: large or small joint involvement, specifically in lower limbs and spine (axial
involvement, symmetry); progression to polyarthritis
Psoriatic: Chronic arthritis and psoriasis OR arthritis with 1st degree family history of psoriasis plus
dactylitis or fingernail abnormalities
Presentation: peripheral and axial arthritis that presents asymmetrically in small and medium
joints, developing into juvenile spondyloarthropathies and may develop into uveitis
Lab findings: +/- HLA B27 and usually RF negative
Note: arthritis can precede psoriasis by many years
Henoch-Schonlein Purpura: IgA vasculitis (most common type of systemic vasculitis in children)
Presentation: 1. Palpable purpura without thrombocytopenia and coagulopathy
2. arthritis/arthralgia: oligoarticular, transient, present in lower extremities and buttocks; + periarticular
swelling/tenderness; no joint effusion, erythema or warmth; pain and limited ROM
3. Abdominal pain
4. Renal disease: hematuria/proteinuria/nephrotic syndrome, HTN, and renal insufficiency
5. Rarely: Cerebral disease
Complications: 1. Belly: primary initial morbidity
2. *Kidney (most serious/common late complication): nephrotic syndrome, HTN, renal insufficiency
3. Brain: hemorrhage
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4. Skin (purpura, hemorrhage/anemia)
5. Joints (acute arthritis without degeneration resolves with NSAID’s or steroids)
Testing: *Monitor BP and UA for renal complications weekly and then at longer intervals if normal
Prognosis: initial episode typically resolves within 1 month (67% don’t reoccur)
Symptoms of dermatomyositis
Epidemiology: peak age in children 4-10Yo
more common in girls than boys
more common in African Americans
Presentation:
1. Progressive symmetric proximal muscle weakness, generally present in the girdle and lower
extremities
2. Constitutional symptoms: anorexia, weight loss, malaise/fatigue (meaning general feelings of
unwellness and tiredness)
3. Classic Cutaneous findings:
1. Gottron Papules
Pathognomonic, shiny, erythematous: atrophic scaly plaques over extensor surfaces of the
joints
2. Heliotrope Rash!
Accompanied by: malar/facial erythema and photosensitivity
3. Others: periungal capillary changes (dilated capillaries in nail bed; tortuosity and dropout in
blood vessels),
calcinosis cutis, ulcerations (skin and organ), arthralgia/arthritis
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Diagnostic Criteria: Must have typical skin findings (heliotrope rash, Gottron’s papules, nailbed capillary
findings, dystrophic calcinosis) PLUS 2 of the following criteria:
Progressive symmetric weakness of limb-girdle muscles
Elevation of serum muscle enzymes (e.g. CPK, aldolase, LDH, AST, ALT)
Myopathy on electromyogram
Inflammatory myositis on muscle biopsy
Complications: Cutaneous: calcinosis, scarring or atrophy, or lipodystrophy; muscular: respiratory
failure; Skeletal: osteoporosis, joint contractures, avascular necrosis, arthropathic deformity; Pulmonary;
Infection; Gastrointestinal
Treatment: When in acute phase: high dose steroids (oral or IV); Immunosuppressive agents:
methotrexate, cyclosporine, cyclophosphamide (severe/life-threatening disease), biologic agents;
Supportive/Preventative: Sunscreen, topical skin care; Osteoporosis: calcium/Vitamin D; Physiotherapy
for aerobic endurance and contractures
Diagnosing pediatric SLE
Lab Findings:
HALLMARK: autoantibody production against self-antigens
Antinuclear antibodies (ANA) to DNA: most commonly positive in children with SLE
Anti-Smith- sensitivity> specificity
Anti-dsDNA- best combo of specificity and sensitivity
Complications of HSP
Severity typically correlates with initial presentation… <1% develop complications, not including those
who develop complications LATE
1. Belly: primary initial morbidity
2. *Kidney (most serious/common late complication): nephrotic syndrome, HTN, renal insufficiency
Refer to a nephrologist for: persistent proteinuria, HTN, renal insufficiency
3. Brain: hemorrhage
4. Skin (purpura, hemorrhage/anemia)
5. Joints (acute arthritis without degeneration resolves with NSAID’s or steroids)
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Lecture 26 – Rheumatic Disease (Berglind)
Reiter’s syndrome immunology
Involves: HLA-B27 and Molecular Mimicry
Pathogenesis: Pathogens, such as, Chlamydia, Yersinia, or Salmonella, mimic auto-antigen and bind to
HLA-B27, causing complement activation, inflammation, fibrosis and, ultimately,Ankylosing
Spondylitis/Reiter’s
RA Immunology
Lab findings/Testing:
1. CBC
2. ESR
3. X-ray
4. Rheumatoid factor (RF): IgM or IgG auto-antibody binding to self-IgG Fc
Cause: auto-antibody binding self-IgG Fc receptor: possibly genetic (HLA-DR4 alleles, PTPN-22, CTLA-4,
PAD14, cytokines) and/or environmental factors (viruses or bacteria) and/or personal health habits
(stress, smoking, diet)
Development of RA:
Molecular mimicry or other factors RA
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5 Stages of RA
Stage 1: healthy synovial joint
Stage 2: synovitis
Stage 3: Pannus development, destroying cartilage and bone
Stage 4: Fibrous Ankylosing (breakdown of bone resulting in a fibrous connective tissue, resulting in a
completely immobile joint)
Stage 5: no pain or swelling despite bone collapse into a single unit (rather than 2 separate bones).
Results in advanced osteoporosis, making joint extension impossible
Pathogenesis:
EARLY RA: movement of immune cells (T cells, B cells, and PMN’s)= synovitis
Edges become hypertrophic
3 Phases of Early RA:
1. Initiation: RF made in normal antibody making process
T cells are KEY initiators of RA pathogenesis, activate B cells and macrophages, which make TNF-α and
IL-1
Types of T cells involved:
Normal: Synovial naïve T cell activates Th17, Th1 cells, which help to regulate other immune
cells/immune response
RA: impaired production/binding of IL-10, TGF-β to Th17 cell and Regulatory T cell so NO DOWNREGULATION of immune response in synovium autoimmunity. PMN’s are activated to release
contents: reactive oxygen species and NO into synovial space.
Autoantibodies: RF
Potential autoantigens: cartilage Ag, Type II collagen, gp39, cartilage link protein, proteoglycans,
aggrecan, Citrullinated peptides (ANTI-CCP: marker of RA), Glucose-6-phosphoisomerase, HLA-DR, Heatshock proteins, heavy-chain binding protein, hnRNP-A2, Immunoglobulins (IgG)
2. Propagation: Immune complex binds Fc receptor on mast cells, leading to mast cell production
of *TNF-α*, IL-1, etc. which leads to tissue damage to bone and cartilage, pannus formation, and
B cell stimulation to produce autoantibodies
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1. Breakdown of immune system tolerance (see Initiation step above)
2. Type III Hypersensitivity: autoantibody binds surface of cell/joint surface
3. Complement activation and recruitment of immune cells: PMN’s, macrophages, and mast cells
through C5aR but there’s a problem with phagocytosis= frustrated phagocytosis!!
4. Pannus formation, production of MMP’s, cytokines and angiogenic factors
3. Tissue Damage to Bone and Cartilage: Osteoclasts activated, Synovial fibroblasts produce MMP,
PGE2, CCL5 and IL-18
Key cytokines in inflammatory arthritis:
TNF-α, IL-1, IFN-γ, IL-6, OPGL/RANKL, IL-17
ESTABLISHED RA: arthritis with formation of pannus (when cells of synovium divide and grow)
Treatment: must account for autoimmunity + inflammation: Anti-TNF drugs= some success in treating
autoimmunity part
SLE immunology
Deficiency in Complement proteins 2 and 4
HLA-DR2 & HLA-DR3 susceptibilities
Pathogenesis
Genes/environmental factors Abnormal immune response Autoantibodies Inflammation
Damage
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Cellular Markers
Lupus Erythematous cell= PMN-ingested nuclear material
Types of Autoantibodies
Anti-nuclear Antibodies
DNA antibodies
DNA-histone complex Antibodies
Non-histone protein Antibodies
Cardiolipin and Phospholipid Antibodies
Pathogenesis Overview:
Genes/Environmental Factors Regulatory T cell not turning off autoimmune response and/or APC’s
antigen presenting to T cells, which activate B cells to make autoantibodies
Triggers: Genetics (C1q, C2, C4 deficiency or IRF5, STAT4 transcription factor deficiency so no
appropriate cytokine production to make correct antibody or to shut down immune response)
environmental factors (including medications/drugs like procainamide)
infections (EBV)
hormones (stress-related, sex steroids)
drugs
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Errors in Immune System:
If deficiency in Fas can’t destroy cells/ lack of normal immune response/ regulation
Role of B cells in SLE:
Become hyperactive and continuously secrete auto-antibody
Role of T cells in SLE:
T regulatory cells aren’t shutting down the autoimmune response and becomes immunogenic and
causes production of pro-inflammatory cytokines
Role of Macrophages in SLE:
Defect in clearance, overproduce interferons, IL-10, ROS
Drug Targets:
Cytokine inhibitors (anti-IL-1, anti-IL-6, etc.)
Inhibition of B cell survival
Other targeted therapies (JAK3 inhibition)
Plus Some other Stuff
Arthralgia
Joint pain
vs
Arthritis
joint inflammation
Pain, redness, swelling, increased
warmth, fluid accumulation, stiffness
Why does [central and/or peripheral] tolerance fail?
CTLA-4, apoptosis processes
Principal fate of lymphocytes that recognize self-antigens in the generative organs is death (deletion)
BUT: some B cells may initiate T cells’ specificity into regulatory (suppressive) T lymphocytes
Lecture 27 – Immune Mediated Musco… (Kilgore)
Reiters etiology
Classic Triad: “you can’t see, you can’t pee, and you can’t climb a tree”
Conjunctivitis: may see anterior uveitis
Arthritis: asymmetric and additive/mostly lower extremities
Urethritis: urogenital lesions/cervicitis/prostatitis
Symptoms start 1-4 weeks after infection and may include: fever, fatigue, malaise, weight loss,
musculocutaneous lesions, oral ulcers, and vesicles on palms and soles
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Acute episode of arthritis that follows an episode of enteric or urogenital infection
Epidemiology: more common in HLA-B27 positive patients
Causes: enteric pathogens: specifically Salmonella, Shigella, Yersinia, and Campylobacter jejunii
OR non-enteric/genitourinary pathogens: Chlamydia
Treatment:
NSAID’s for acute arthritis
antibiotics for treatment of acute non-gonococcal urethritis
intralesional glucocorticoid injections for severe tendonitis
glucocorticoids to prevent blindness from uveitis
SLE epidemiology and diagnostic criteria
Systemic Lupus Erythematous: multisystem, autoimmune disorder of unknown etiology that is strongly
associated with various autoantibodies
Epidemiology: women to men (7-15:1)
Causes: genetic, immunologic, hormonal and possibly environmental factors
Presentation: Cutaneous: facial “butterfly” rash, discoid lesions, oral and nasal mucosa ulcers, alopecia;
Renal: lupus nephritis (most serious finding): classified from I-IV and is the leading cause of mortality in
the 1st decade of diagnosis. If untreated, lupus nephritis will develop into end-stage renal disease and
require dialysis or transplant
CNS: headache, seizure, psychosis, Transischemic attack/Cerebral vascular attack (both are types of
stroke)
Vascular: Raynaud’s (excessively reduced blood flow in response to emotional stress), hypercoagulable
state (due to anticardiolipin antibodies, lupus anticoagulant and antiphospholipid antibodies), deep vein
thrombosis, vasculitis, and peripheral emboli
Cardiac: pericarditis, pericardial effusions, Libman-Sacks endocarditis, myocardial infarction
Lab findings: + ANA in >95% of SLE patients, high titers of dsDNA antibodies, anticardiolipin antibody,
lupus anticoagulant CBC: low WBC, low platelets and NCNC anemia
UA: elevated protein
Criteria: Any combination of 4+ of the below criteria whether documented contemporaneously or not,
indicates a diagnosis of SLE (specificity: 95%, sensitivity: 75%)
1. Malar Rash: fixed erythema, flat or raised, over the malar eminences
2. Discoid Rash: erythematous circular, raised patches with adherent keratotic scaling and follicular
plugging; possible atrophic scarring
3. Photosensitivity: exposure to UV light causes rash
4. Oral ulcers: oral and nasopharyngeal ulcers (must be observed by physician)
5. Arthritis: nonerosive arthritis of 2+ peripheral joints accompanied by tenderness, swelling or
effusion
6. Serositis: pleuritic or pericarditis documented with ECG or heart rub or effusion
7. Renal Disorder: proteinuria >0.5g/d or 3+ or cellular casts
8. Neurologic disorder: seizures of psychosis without other causes
9. Hematologic disorder: hemolytic anemia or leukopenia (<4000/L) or lymphopenia (<1500/L) or
thrombocytopenia (<100,000/L) in the absence of offending drugs
10. Immunologic disorder: Anti-dsDNA, anti-Sm and/or anti-phospholipid
11. Antinuclear antibodies: abnormal titer of ANA by immunofluorescence or an equivalent assay at
any point in time in the absence of drugs known to induce ANA’s
Treatment: NSAID’s, topical steroids, IV/oral steroids, Hydroxychloroquine, Cyclophosphamide,
Azathioprine
Prognosis: ~25% of cases may have remissions; 5-10 years: 90% survival rate; 20 years: 78% survival rate
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Leading cause of death: renal failure, infections and thromboembolic events
Diagnosing Sjogrens
Slowly progressive autoimmune disorder caused by lymphocyte infiltration of exocrine glands.
Types:
Primary Sjogren’s: Sicca syndrome (dry eyes, dry mouth) and parotid enlargement
Secondary Sjogren’s: result of ~30% of other rheumatic diseases
Epidemiology: more common in middle-aged women than men (9:1)
Presentation: Extra-glandular: arthralgia/myalgia, Raynaud’s, GI- low grade pancreatitis/atrophic
gastritis, lymphoma
Lab Findings: elevated ESR, anti-Ro/SS-A and Anti-La/SS-b, mild normochromic normocytic anemia
Labial biopsy with focal lymphocyte infiltration
Abnormal tear flow by Schirmer’s test (<5mm in 5 min)
CREST syndrome
Type of systemic sclerosis (chronic systemic disorder characterized by skin thickening and variable
visceral vasculitis and/or fibrosis)
Characteristics:
C-Calcinosis cutis
R- Raynaud’s
E- esophageal dysmotility
S-sclerodactylyl
T-telangiectasias
Ankylosing spondylitis epidemiology
Type of spondyloarthropathy, which are a related group of inflammatory disorders with clinical features
unique among rheumatic diseases.
4 Cardinal Features of spondyloarthropathy:
1.
2.
3.
4.
Sacroilitis: inflammation of SI joints
Spondylitis: inflammation of the spine
Enthesitis: inflammation of tendon insertion sites
Uveitis: inflammation of anterior chamber of the eye
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4 Types: Ankylosing spondylitis, Reactive arthritis, Enteropathic arthritis, Psoriatic arthritis
Epidemiology: more common in adolescent boys and young men than girls (2-3:1)
Strong association with Human Leukocyte Antigen (HLA-B27), especially among Caucasions with
Ankylosing Spondylitis (~90%)
Prevalence: 4-5% in working adults with chronic low back pain
Classic Feature: bamboo spine (fusion between vertebral bodies)
Treatment: NO cure.
Early Disease: NSAID’s and PT
Severe flares: IV Corticosteroids or immunosuppressants
(e.g. infliximab, TNF-antibody)
Lecture 28 – Nonsurgical knee (Jacobus)
Diagnosing gout
Aspiration: exam microscopically for crystals
Synovial fluid testing:
1. Uric acid crystals are needle-like crystals with strong negative birefringence under polarized light
2. Cell count: WBC >50,000 is strongly indicative of infection
3. Gram Stain and culture
Regular CBC, ESR, and CRP from blood
Refer for surgical I&D (incision & drainage): to release pus or pressure build-up under the skin; basically,
a minor procedure to clean out infected area and promote healing
Prepatellar cellulitis vs. septic knee
Knee infections: 90% of the time, knee joint should be opened and cleaned out to prevent re-infection
Prepatellar cellulitis
Bacterial infection of the deep layers of the skin- subcutaneous and dermis- and generally caused by
Staph or Strep
Presentation: Erythema, warmth, NO effusion, tenderness with superficial palpation, painless ROM
Testing: NO aspiration.
Regular CBC, may or may not see an elevated WBC
Treatment: antibiotics and observation
Septic knee
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MCL strain vs. ACL tear vs. meniscal tears
Medial views
MCL strain
Generally due to valgus stress
http://www.sportsinjuryclinic.net/sport-injuries/knee-pain/mcl-sprain
Testing: Valgus stress applied while knee in 30° of flexion: + if pain when stress applied to outside of
knee
Grading:
Grade 1: no opening, just pain
Grade 2: some opening with endpoint
Grade 3: no endpoint
Treatment: if an isolated MCL injury, use a brace. Non-arthroscopic surgery only if the MCL has been
torn from its insertion on the femur or tibia using large stitches, metal screws, or bone staples OR if MCL
tear in the middle, in which case the surgeon will sew the torn ends together.
ACL tear: when you plant your foot and then twist knee
Presentation: unsteadiness in climbing and descending stairs
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Meniscal Tear
Meniscus only has blood supply only on the periphery
Locking or catching of knee with movement
Treatment: scope surgery remove portion of meniscus with tear; rarely attempt to repair due to lack of
blood supply to the meniscus
#1 reason for hemarthroses/bleeding occurring in a joint
ACL injury causes acute swelling of the knee joint and indicates serious injury
Location and anatomic relationship of pes anserine bursa
Normal: The pes anserinus (anserine) bursa, along with its associated tendons, is located along the
proximomedial aspect of the tibia. –Medscape
Disorder (Pes Anserine Bursitis): tendon insertion along proximal tibia gets pulled out, causing swelling of
pes anserine bursa
Common in: mid-teens
Treatment: Conservative; if needed, injection therapy of platelet rich plasma; no surgery unless significant
instability with varus stress causing wide opening of that side of the patella
Lecture 29 – Surgical Treatment of Knee Injuries (Jacobus)
Why women have more ACL tears than men
Normal: Intercondylar notch of femur in women is ½ as thick as it is in men and it has been noted that
their smaller notch is correlated with a thinner ACL.
Disorder: ACL tear due to #1 narrower width of intercondylar notches of femur and possibly other
factors, including limb alignment, muscle imbalance, and ACL width
Note: Shoe type (such as high heels and flip-flops) changes the ligamentous structure of your leg
Prevention: Brace often used in contact sports for knee injury prevention
Note: spontaneous healing of ACL since blood supply is generally disrupted
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Treatment:
Don’t operate if: no meniscus tear. No cartilage injury. Low activity level prior to injury.
Operate if: Delays in surgery lead to additional injuries. Additional injuries lead to worse outcomes.
Delayed surgery leads to inferior outcome. Recommend that reconstruction be performed without
undue delay once swelling has subsided and ROM is restored.
Partial Tear:
In asymptomatic patients: non-operative management like bracing
In symptomatic patients or patients progressing to complete tear: reconstructive surgery
Complications: 1. meniscus injury 2. chondral injury 3. Development of Osteoarthritis as a later
complication of ACL deficient knees.
OA Preventative Treatment: HA or PRP injection to replace viscosity of fluid and lubricate joint
Surgical treatment of ACL injuries (see slide 47)
Operate if: Delays in surgery lead to additional injuries (e.g. meniscus tears, degenerative changes)
Additional injuries lead to worse outcomes (e.g. intra-articular joint damage or meniscal injury)
Delayed surgery leads to inferior outcome
Recommend that reconstruction be performed without undue delay once swelling has subsided and
ROM is restored.
Principles of ACL Reconstruction:
1. Harvest of autograft (from patient- different area of body) /Prep of allograft (usually from cadaver
or synthetic)
Must be contoured to fit tibial tunnel ~10mm
Suture placed in both ends of graft
2. Diagnostic arthroscopy
Typical entries/portals: lateral to medial parapatellar
OR superomedial
Once inside, use scope to look for meniscal pathology,
Chondral injury, and loos bodies
3. Address meniscal pathology
If meniscal pathology present, address by debridement
and repair
Evaluate ACL tear
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4. Debridement/Notchplasty
Debride ACL stump and fibrous tissue from wall of lateral femoral condyle
Notchplasty: removal of 3-5mm of bone from femoral condyle, preventing impingment of graft
when knee is in full extension.
Resident’s Ridge: ridge of bone on lateral wall of the notch can be mistaken for the posterior
border of the notch. True posterior wall of intercondylar notch lies ~1cm posterior to Resident’s
Ridge.
5. Tunnel preparation
Tibial tunnel will be found posteromedial aspect of the tibial footprint, centered ~7mm anterior
to PCL. Externally, guide is placed midway between tibial tubercle and periormedial aspect of tibia.
Use guide wire drilled
**Slide 47: Femoral Tunnel Placement
Offset guide should be placed on “over the top” position, engaging the posterior cortex
Graft should be placed as far posterior as possible; anterior placement is a common cause of failure
6. Graft placement and fixation
Once tunnels are drilled, Beath needle passed through both tunnels, exiting the anterolateral
thigh
Sutures tied to graft are attached to Beath needle.
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Graft is pulled through both tunnels into position by pulling on needle
Femoral bone block is fixed with a cannulated interference screw placed anterior to the bone
block.
Tibial side of graft is secured with interference screw.
OVERALL: reliably restores stability and allows individual to return to high (impact?) activity
Options for Graft Fixation:
Crosspin fixation: soft tissue graft is looped around metal pin inside femoral tunnel.
Endobutton fixation: graft is brought through femur and fixed at lateral cortex.
Autograft
BPTB (bone-patella tendon-bone grafts)
Hamstrings
Quadriceps
vs
Allograft
BPTB
Achilles
Quadriceps
Tibialis Anterior/Posterior
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Autograft
Pros
vs
Low risk of inflammatory reaction
No risk of disease transmission
Potentially more rapid incorporation
Potentially less expensive
Complications: OA after ACL Reconstruction
Cons
donor site morbidity
MCL strain vs. ACL tear vs. meniscal tears
MCL strain
Generally due to valgus stress
http://www.sportsinjuryclinic.net/sport-injuries/knee-pain/mcl-sprain
Testing: Valgus stress applied while knee in 30° of flexion: + if pain when stress applied to outside of
knee
Grading:
Grade 1: no opening, just pain
Grade 2: some opening with endpoint
Grade 3: no endpoint
Treatment: if an isolated MCL injury, use a brace. Non-arthroscopic surgery only if the MCL has been
torn from its insertion on the femur or tibia using large stitches, metal screws, or bone staples OR if MCL
tear in the middle, in which case the surgeon will sew the torn ends together.
ACL tear
Cause: ACL tear/rupture typically occurs during a noncontact deceleration event that produces a valgus
twisting injury. E.g. basketball player lands on one leg and quickly pivots in opposite direction ACL
tear, usually due to hyperflexion injury (sometimes hyperextension but hyperextension often causes PCL
injury)
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Presentation: hemarthrosis within a few hours of injury b/c blood to knee runs through ACL (as well as
PCL and peripheral meniscus). Patient often describes injury similar to above and states they hear or feel
a “pop” and patient is unable to resume normal activities.
Testing: + Lachman’s (most sensitive) and + Anterior Drawer
**Most important test: MRI (95-100% accuracy) for diagnosing ACL tear
Complications:
Magnetic resonance images of bone bruise patterns (lateral femoral condyle and posterolateral tibial plateau)
associated with acute anterior cruciate ligament (ACL) injury. A: Sagittal plane view shows the more posterior location
of the tibial bruise relative to the femoral bruise. Arrows point to the hyperintense signals associated with bone
bruises. B: Frontal plane view shows lateral compression of the femur and tibia
From: http://lermagazine.com/article/bone-bruises-and-risk-of-knee-osteoarthritis
1. Bone bruise is a hidden fracture of the bone that involves the middle portion of the lateral femoral
condyle (valgus stress on knee) and posterior lateral tibial plateau (anterior translation of tibia)
Diagnosis: visible on MRI that you already ordered for the suspected ACL tear
Note: bone bruising occurs in 85% of acute ACL injuries
2. Associated Meniscus Injury: MCL, LCL, or meniscus;
Note: Meniscus tears occur with 50-75% of acute ACL tears
3. Lateral Meniscus Triad: ACL, MCL and lateral meniscus (more common of the two triads)
4. Classic Triad of O’Donoghue: ACL, MCL and medial meniscus
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Meniscal tear
Treatment: SURGERY unless tear is on periphery b/c central meniscus is naturally avascular and cannot
repair on its own
Indications for total knee arthroplasty
Limited walking tolerance less than 1 block
Attempted physical therapy, tried NSAID’s, injections, walker…. To no avail….
Limitations of activities of daily living (ADL)
Acceptable medical risk
Surgical meniscal tear repairs
Red zone is vascularized; white
zone is avascular
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Presentation: often atraumatic or chronic cause with pain, swelling and catching feel. Joint line
tenderness
Testing: MRI, + McMurray’s
Most tears need to be debrided
Repairs have a higher complication and failure rate
Repairs are most often successful when paired with an ACL reconstruction
*Peripheral tears can be repaired because their blood supply is from the periphery while central repairs
should be debrided/ removed because they will not heal as they are naturally avascular
Meniscal allografts relieve pain and may not affect arthritis risk
Meniscal Surgery Types
Resection
Repair
Replacement
Allograft
Scaffolding
Limitations: longer recovery, poor vascularity with significant re-tear rate, higher complication rate
(nerve, vessel, device) and adjuncts to improve success (e.g. fibrin clot, enriched plasma, growth factors)
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