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DRx Rheumatology Module
Rheumatology Module
255
Medical
Graduate
09/06/2013

Additional Medical Flashcards

 


 

Cards

Term
Pathologic Autoimmunity
Definition

1. Immune reaction specific for self antigen

2. Evidence that the reaction is not secondary to tissue damage

3. Absence of a well defined cause for the disease

Term
Antibody Mediated Autoimmune Diseases
Definition

1. Organ-specific autoimmune diseases

- Autoimmune hemolytic anemia

- Atuoimmune thrombocytopenia

- Myasthenia gravis

- Graves disease

- Goodpasture's syndrome

2. Systemic autoimmune diseases

- Systemic lupus erythematosus

3. Diseases due to autoimmunity or reactions to microbial antigens

- Polyarteritis nodosa

Term
T-cell Mediated Autoimmune Diseases
Definition

1. Organ-specific Autoimmune Diseases

- Type I diabetes mellitus

- Multiple sclerosis

2. Systemic diseases

- Rheumatoid arthritis

- Systemic sclerosis/Scleroderma

- Sjogren's syndrome

3. Diseases due to autoimmunity or reactions to microbial antigens

- Inflammatory bowel disease

- Inflammatory myopathies

Term
Self-Tolerance
Definition

- Unresponsive or absent lymphocytes as a result of prior exposure to the antigen

- Central: Develops in the thymus or bone marrow

- Peripheral: Develops in the periphery

- Alloantibody=Isoantibody --> Antibody produced by on individual that reacts with antigens from another individual of the same species

- Antibody-Antigen binding results in immune complex formation and agglutination

Term
Central Tolerance
Definition

- During development, lymphocytes are generated that react with multiple epitopes, even self-antigens

- Lymphocyte clones directed against self are deleted in the thymus

- At birth only lymphocytes and antibodies to non-self antigens remain

- Negative selection: Auto-reactive lymphocytes deleted in the thymus (T-cells) and bone marrow (B-cells)

- Presentation of peripheral antigens in the thymus: Through autoimmune regulator protein (AIRE) expression within cells in the thymus

- Mutated AIRE protein --> Autoimmune disease

- B-cells: Undergo a second session of re-arrangement after they first react with self-antigens

Term
Peripheral Tolerance
Definition

- Elimination of autoreactive T or B-cells in the periphery

1. T regulated cells: Normal, self-reactive T-cells that escape the thymus --> Normally act to suppress APCs in the periphery

- Requires IL-2 and FoxP3 expression

2. Activation Induced Cell Death --> Apoptosis

- Mitochondrial or Death Receptor Pathway activation

3. Anergy: Lymphocytes normally need 2 signals to become activated

- CD28 co-stimulatory molecule --> Activation

- CTLA4 co-stimulatory molecule --> Anergy

- Increased expression of CTLA4 in anergic lymphocytes

Term
Type II Hypersensitivity Reactions
Definition

- IgG and IgM mediated reaction

- Antibodies either block or improperly activate receptors throughout the body, causing disease

Term
Type II Hypersensitivity Autoimmune Diseases
Definition

- Autoimmune thrombocytopenic purpura: Targets platelet membrane proteins --> Opsonize and phagocytose platelets --> Bleeding

- Pemphigus vulgaris: Target intracellular junction proteins --> Activation of proteases and disruption of adhesions --> Skin flaccid vesicles

- ANCA pos. Vasculitis: Neutrophil granule proteins (target) --> Neutrophil degranulation and inflammation --> Vasculitis

- Goodpasture Syndrome: Non-collagenous proteins in BM --> Complement and Fc receptor mediated inflammation --> Nephritis and lung hemorrhage

- Insulin-resistant Diabetes: Insulin receptor inhibition --> Hyperglycemia and ketoacidosis

- Pernicious anemia: Intrinsic factor degeneration --> Abnormal erythropoiesis and anemia

Term
Type III Hypersensitivity Reaction
Definition

- Immune complex mediated

- IgG antibodies produced to self-antigens

Term
Type III Hypersensitivity Autoimmune Diseases
Definition

- SLE: Nuclear antigens (ANA) --> Nephritis, skin lesions, etc

- Post-streptococcal Glomerulonephritis: Streptococcal cell wall antigens --> Nephritis

- Polyarteritis nodosa: HBV antigens --> Systemic vasculitis

- Reactive arthritis: Bacterial antigens

- Serum sickness: Various proteins --> Arthritis, vasculitis, and nephritis

Term
Type IV Hypersensitivity Reaction
Definition

- Delayed type

- T-cell mediated

- Th1 and Th17 CD4 T- cells involved

- CD8 cytotoxic T-cells also involved

Term
Type IV Hypersensitivity Autoimmune Diseases
Definition

- Type I Diabetes: Antigens of pancreatic islet B cells --> Destruction of B cells and diabetes

- Multiple Sclerosis: Protein antigens in CNS myelin --> Demyelination in CNS, paralysis and ocular lesions

- Rheumatoid arthritis: Unknown antigen --> Chronic arthritis

- Crohn disease: Commensal bacteria?? --> Chronic intestinal inflammation and obstruction

- Peripheral neuropathy/Guillan-Barre: Protein antigens of peripheral nerve myelin --> Neuritis and paralysis

Term
Immune Privileged Sites
Definition

- Testes, brain, and eye

- No immune response because the antigens are never presented to the immune system

- If presented to immune system --> Can induce autoimmune disease

- Usually following traumatic injury to these sites

Term
Genetic Suspectibility to Autoimmune Disease
Definition

- Definite genetic component --> Unclear what exactly it is for all diseases

- Several HLA genes 

- Mutations may alter negative selection and central tolerance

Term
Infections and Autoimmunity
Definition

- Autoimmune diseases may have an icrease in symptoms after infections

1. Generalized increase in co-stimulatory molecules --> All lymphocytes in circulation are activated

2. Molecular mimicry: Immune response directed towards bacterial/microbial antigen cross-reacts with self antigen

3. Polyclonal B-cell activation

4. Infection induced cell damage and alteration of self antigens

5. Enhanced local recruitment of lymphocytes

Term
Progression of Autoimmune Diseases
Definition

- Normally the antigen is completely eliminated after immune response is mounted

- Antigen is never eliminated in autoimmune disease --> Negative feedback loops do not become activated and immune response never stops

- Cell and tissue damage may create or uncover antigens that are new to the immune system and may cross-react

- Epitope spreading: Spread of the immune response to these new antigens

- Lots of clinical overlap between autoimmune diseases supports the epitope spreading theory

Term
Rheumatoid Arthritis (RA)
Definition

- Chronic, destructive, inflammatory arthritis --> Commonly flares

- Joint involvement: Small joints of the hands and feet --> Symmetrically --> No DIP involvement

- Extra-articular features are common

- Prevalence: 0.4-1% worldwide, 2x more common in females

- Usually presents before age 45

- Smoking: 1.5x risk

- Genetics: HLA-DR1 and HLA-DR4

- Types: Flaring, relentlessly progressive (10%), episodic/palindromic rheumatism, and monophasic (10-20%)

Term
Rheumatoid Arthritis History and Exam
Definition

- Joint pain and swelling

- Morning stiffness usually lasting more than an hour, improves with movement and recurs with inactivity

- MCPs and PIPs often involved but NOT DIP joints

Term
Extra-Articular Features of RA
Definition

- Fatigue, weight loss, and rarely fever

- Rheumatoid nodules (10-20%) --> Commonly on elbows

- Pleuritis > Pericarditis > Peritonitis (>10%)

- Sjogrens (10%)

- Interstitial lung disease (9%, but now declining)

- Eye: Episcleritis, scleritis, uveitis, and keratitis

- Vasculitis

- Felty's syndrome --> Splenomegaly and leukopenia

- Amyloidosis: 1-5%

Term
Lab Tests for RA
Definition

1. Autoantibodies

- Rheumatoid Factor (RF): IgM/IgG antibodies binding the Fc portion of IgG antibodies --> Present in up to 90% of patients

- Anti-citrullinated-protein antibodies (ACPA): Binds protein epitopes that contain citrulline (60-75% of patients)

2. Non-specific tests

- High ESR and CRP

- Mild/moderate anemia, low iron and TIBC, and mildly low albumin

Term
Imaging for RA
Definition

- Early RA: X-rays often show only soft-tissue swelling so useless for early RA --> MRI or ultrasound will show synovitis that may not be present on exam

- Long-standing RA: Marginal erosions and joint space narrowing seen on X-rays

Term
Joint Damage in RA
Definition

- High risk of permanent joint damage --> Much more common in seropositive RA

- Ulnar deviation of MCPs with radial deviation of the wrist

- Joint subluxation at the MCPs, PIPs, and wrists

- Atlanto-axial instability --> Paraplegia possible

- High rate of occupational disability

- High rate of joint replacement surgery

- Boutonneire deformity: PIP flexion with DIP hyperextension

- Swan Neck Deformity: Hyperextension of PIP with flexion of DIP joint

Term
Treatment of RA
Definition

1. Disease-Modifying Anti-Rheumatic Drugs (DMARDs)

- Methotrexate: Weekly

- Leflunomid

- Azathioprine and cyclosporine

- Hydrochloroquine and sulfasalazine

- Gold, penicillamine and minocycline

2. Biologics

- Anti-TNF: Etanercept and infliximab

- Abatacept: CTLA-4-Ig

- Rituximab: Anti-CD20 --> Depletes B cells

- Tocilizumab: Anti-IL-6R

- Anakinra: Anti-IL-1

- Tofacitinib: JAK inhibitor

3. Corticosteroids

- Early in treatment course for rapid control or for flares

4. NSAIDs

Term
Juvenile Idiopathic Arthritis (JIA)
Definition

- Previously called Juvenile Rheumatoid Arthritis

- Chronic inflammatory arthritis beginning before age 6

- ~1:1000 --> Highest with European descent

- More likely to resolve than adult RA

- High rate of uveitis --> 3-16%

- Subtypes: Systemic onset, oligoarthritis, polyarthritis, and spondyloarthropathy

Term
Presentation of JIA
Definition

- Usually presents with dysfunction instead of pain --> Noticed by parents

- Differential diagnosis of arthritis in children is quite different for adults --> Periodic fever syndromes, leukemia, and congenital skeletal diseases

- Different metabolism of meds --> Must take into account

- Growing skeleton can change things

- Growth retardation from chronic inflammation or glucocorticoids --> Micrognathia

- Accelerated growth due to increased blood flow to the bone epiphysis --> Leg length discrepancy with the affected leg being longer

- C-spine or wrist fusion are possible

Term
Subtypes of JIA
Definition

1. Systemic onset: Fever and rash (salmon-colored)

- Macrophage activation syndrome: Hemophagocytic anemia --> Microangiopathy, low fibrinogen, platelets, leukopenia, anemia, high AST/ALT, and VERY high ferritin (>10,000)

- Treatment: Prednisone, IL-1 blocker, and IL-6 blocker

2. Oligoarthritis: 1-4 joints involved --> Especially knee

- Most common type

- Usual onset before age 5

- ANA+ in 40-80%

- Higher risk of uveitis

- Treatment: NSAIDs, intra-articular steroids, MTX, and biologics

3. Polyarthritis: >5 joints

- RF-neg: Knees, wrists, ankles, MCP, PIP, hip and shoulder

- RF-pos: Usually >12 years, often +ACPA, small joints, and persists into adulthood

- Treatment: DMARDs and biologics

4. Spondyloarthropathy: Psoriatic, enthesitis, and spondylitis

Term
Sjogren's Syndrome
Definition

- Autoimmune disease of salivary and lacrimal glands

- Associated with RA or lupus (Secondary)

- Extra-glandular manifestations common

- Prevalence: 0.6-3% --> 9x mroe females

- Genetics: HLA-DQA1, HLA-B8, and HLA-DR3

- Viral trigger?? --> HCV infection

- 50-80% ANA +

- 90% Ro and La +

- 75% RF+

Term
Presentation of Sjogren's
Definition

- Dry eyes: Lacrimal gland enlargement, conjunctival erythema, and corneal ulcerations

- Dry mouth: Salivary gland enlargement, reduced salivary pooling, and dental caries

- Dryness everywhere: Nose, upper airway, vagina, and skin

Term
Extraglandular Features of Sjogren's
Definition

- Arthralgias or arthritis (70-75%)

- Raynaud's (40-50%)

- Interstitial nephritis with renal tubular acidosis (7-9%)

- Liver, overlap with autoimmune hepatitis or primary biliary cirrhosis (4-5%)

- Neuropathy --> Cranial, peripheral, and small fiber

- CNS involvement --> Controversial

- Vasculitis --> Purpura (5%)

- Lymphoma (0.5-2%) --> 6-40x increased risk

Term
Diagnosis of Sjogren's
Definition

- Not everyone with dry eyes and/or dry mouth has Sjogren's

- Autoantibodies: Anti-SSA (Ro) in 40-60%, anti-SSB (La) in 50%, and RF

- Specialized exams: Schirmer test, rose bengal, lissamine green stain, sialometry, sialography, scintigraphy, and MRI

- Biopsy of minor salivary gland --> Usually on the lip

Term
Treatment of Sjogren's Syndrome
Definition

1. Dryness

- Topical lubricants

- Good dental care

- Cyclosporine eyedrops

- Cholinergic agents: Pilocarpine and cevemiline

2. Extra-glandular disease

- Mild: Hydroxychloroquine and low-dose prednisone

- More severe: High-dose steroids, methotrexate, azathioprine, rituximab, and cyclophosphamide

Term
Systemic Lupus Erythematosus (SLE)
Definition

- Relapsing and remitting multi-system disease

- Associated with the formation of autoantibodies with multiple specificities

- Broad range of severity

- Prevalence: 1 in 2,000-2,500 --> 8x more females

- More common in African Americans

- Peak age of onset --> 20-40 years

- 10 year survival rate --> 93%

- Genetic predisposition --> 20x risk to close relatives

- Rare deficiencies in complement --> 20-90% risk of SLE with complement deficiencies

Term
Pathogenesis of SLE
Definition

1. Autoimmunity to multiple antigens

- Breakage of self-tolerance in T and B cells

- Role of innate immune cells --> Striking upregulation of IFN-a pathway and antigen presentation

2. Immunopathology

- Autoantibody-mediated damage --> Immune complexes and other mechanisms

- T-cell mediated damage --> Discoid lupus

Term
Clinical Features of SLE
Definition

- Photosensitivity (50%)

- Malar rash (71%) --> Flat or raised fixed erythema

- Discoid rash --> Raised with plugging/scarring/scaling

- Oral ulcers --> Painless

- Fever (48%)

- Arthritis (80%) --> Non-erosive, 2+ peripheral joints

- Serositis --> Pleural or cardiac (44%)

- Renal disorder --> Proteinuria or cellular casts

- Neurological disorder --> Convulsions or psychosis without other cause

- Hematological disorder --> Haemolysis and cytopenia

- Immunological disorder --> Anti-dsDNA, anti-Sm, and antiphospholipid antibodies

- Antinuclear antibody (ANA) (97%)

Term
Cutaneous SLE
Definition

- Malar rash

- Non-specific dermatitis in other locations

- Chronic cutaneous/discoid lupus (DLE)

- Subacute cutaneous lupus (SCLE)

- Cutaneous small-vessel vasculitis --> Palpable purpura, often on palms and soles with urticaria

- Raynaud's phenomenon

- Urticaria

- Alopecia --> common but non-specific to lupus

Term
SLE Malar Rash
Definition

- Erythematous rash of the malar folds

- Photo-exposed areas

- Nasolabial fold sparing --> Identifying feature

Term
SLE Discoid Lesions
Definition

- Hypopigmented, atrophic and scarring macules

- Usually on the hands and arms

Term
Subacute Cutaneous Lupus
Definition

- Raised and scaling rash

- Non-scarring but can become hyperpigmented after healing

- Located on the shoulders and back usually

Term
Vascular Signs of SLE
Definition

- Raynaud's phenomenon --> Usually not vasculitic

- Vasculitis --> Cutaneous small-vessel (common) with large vessels uncommon --> Can show up on the palms and soles

- Thromboembolic disease --> Can lead to ulcers and gangrenous lesions

Term
Musculoskeletal Features of SLE
Definition

1. Symmetric polyarthritis of small joints

- Usually not destructive

- 10% is destructive --> Rhupus

- Subluxation without cartilage loss or bone erosion --> Reducible deformities

- Jaccoud's arthropathy --> Reducible swan neck deformities

2. Myalgia or mysoitis

- Myalgia is common --> Unclear origin

- Myositis is uncommon --> weakness > pain

3. Osteonecrosis --> Avascular necrosis (common)

Term
Visceral Manifestations of SLE
Definition

1. Serositis: Common, painful and usually not dangerous

- Pleuritis > pericarditis > peritonitis

- Not always accompanied by effusion

2. Renal: Common and dangerous

- Asymptomatic --> Nephritic --> Nephrotic

- Class II: Mesangial proliferative

- Class III: Focal Proliferative nephritic syndrome (subendothelial)

- Class IV: Diffuse proliferative nephritic syndrome (subendothelial)

- Class V: Membranous nephrotic syndrome (subepithelial)

- Class VI: Advanced sclerosing of >90% of glomeruli

3. Neuropsychiatric

- CNS: Thromboembolic disease, cerebritis, vasculitis, transverse myelitis, headache, etc

- Neuropathy: Cranial and peripheral nerve distributed

4. Hematologic: Anemia, leukopenia (lymphopenia and neutropenia), thrombocytopenia, and anti-phospholipid antibody syndrome

Term
Anti-Phospholipid Antibody Syndrome
Definition

- Autoantibody-mediated coagulopathy: Large percentage of SLE patients have this but only a small number actually develop clots

- Manifestation: Venous clots > arterial clots, recurrent pregnancy loss (2nd tri), vasculitis-like skin disease, and cardiac valve nodules

- Libman-Sacks endocarditis --> Cardiac valve nodules

Term
Cardiac, Pulmonary, and GI Manifestations of SLE
Definition

1. Cardiac

- Libman-Sacks Endocarditis --> Anti-phospholipid Abs --> Asymptomatic

- Myocardial infarction: Anti-phospholipid Abs and accelerated atherosclerosis

- Pericarditis (common)

- Myocarditis (rare)

2. Pulmonary

- Pleuritis (common and not dangerous)

- Pulmonary embolism --> Anti-phospholipid Abs

- Pneumonitis, pulmonary hemorrhage, and pulmonary hypertension

3. Gastrointestinal

- Serositis --> Peritonitis or bowel serosa involvement

- Mesenteric vasculitis --> Lupus enteritis (small vessels), lager vessles (SMA/IMA/Celiac), and possible bowel infarction

- Glandular involvement (common and rarely dangerous) --> Salivary glands, hepatitis, and pancreatitis

Term
Drug-Induced Lupus
Definition

- Lupus-like syndrome caused by drugs

- Common meds: Procainamide and hydralazine

- Rare meds: B-blockers, D-penicillamine, isoniazid, quinidine, propylthiouracil, hydrantoins, trimethadione, and chlorpromazine

- Also now Anti-TNF meds

Term
Labs for SLE Diagnosis
Definition

- Based off CBC, renal function tests, urinalysis, and complement levels

- ANA, Anti-dsDNA, and Anti-Sm

- Low complement levels

- High titer of DNA antibodies

- Leukopenia

- Proteinuria

- Anemia

- Antibodies to cardiolipin

- High Ig levels

- Effusion

- Other autoantibodies: RBC, platelets, and anti-phospholipid are known --> Along with ANA --> Develop immune complexes

- LE cell: Macrophages or neutrophils phagocytose Ab-coated nuclei

- Possible confusion with syphilis due to false-positive VDRL test

Term
SLE Manifestations due to Autoantibodies
Definition

- Definite: Nephritis and dermatitis

- Probably: Serositis, arthritis, and vasculitis

- Nephritis: Anti-dsDNA

- GI involvement?: Anti-Sm

- ANA antibodies: IgG antibodies directed against nuclear antigens

- ~30% of healthy adults have 1:40 titer ANA

- ~5% of healthy adults have 1:160 titer ANA

Term
Conditions Associated with ANA
Definition

- SLE --> 95-99%

- MCTD --> 95-100%

- Systemic sclerosis --> 95%

- Sjogren's Syndrome --> 75-90%

Term
Treatment of SLE
Definition

- Sunscreen

- Education --> Pregnancy complications, etc

- Mild disease --> Corticosteroids, antimalarials, topicals, and belimumab

- Severe disease --> High-dose steroids, cyclophosphamide, mycophenolate, and azathioprine

- Anti-phospholipid Syndrome: Life-long anticoagulation if arterial or venous thrombosis occurs

Term
Low Back Pain
Definition

- 80% of patients will experience it

- 90% due to mechanical injury

- 90% do not seek medical attention

- 90% get better within 2 months

- 90% recur

- 3 joints between two vertebrae: Apophyseal joint, facet joint, and intervertebral discs

- Spine tilts forward while standing and backwards while sitting

Term
Low Back Pain in Pregnancy
Definition

- 1st trimester: Sacroiliac pain while walking

- 3rd trimester: Sway back (hyperlordosis) while standing

- 3rd trimester: IVC pressure nocturnally while sleeping

Term
Intervertebral Discs
Definition

- Largest avascular structure

- Hydorstatic load bearing structure

- Nucleus is 85% water and annulus is 75% water

- Lost 3/4 of an inch from AM to PM

- Nucleus will move anteriorly with extension

- Annulus: 20 concentric bands that criss cross to prevent rupture

- Most vertebrae will fracture before the disc will rupture

Term
Disc Tears
Definition

- Radial and concentric tears work together to allow the nucleus to bulge out through the annulus

- Bulging --> Protruding --> Herniated --> Sequestered

Term
Clinical Low Bain Pain
Definition

- Backache

- Referred pain to the lateral high and leg

- Radicular/Dermatomal pain --> Burning, sharp, lancinating, worse at night, more leg pain and increases with valsalva maneuver 

- Sclerotomal distribution of pain --> Referred pain

Term
Differential for Acute Back Pain
Definition

- Herniated Nucleus Pulposis: Radicular pain in 90% of patients --> L4/L5 (dorsiflex) > L5/S1 (plantarflex)

- Muscle spasm: Unusual to be primary --> Pain gets better while supine

- Fracture: Pain in any position but decreases with immobility, and secondary to trauma

- Osteoporosis: Higher risk of fractures --> Age, sex, FHx, and steroids

- Septic Disciitis/Spondylitis: Unrelieved even immobile and supine, progressive, fevers, and chills

Term
Clinical Presentation of Acute Low Back Pain
Definition

- Muscle spasm: Can't fully extend, pain relieved supine, and usually secondary

- Osteoporotic Fracture

- Chronic Disc Degeneration --> Disc atrophy and bone spur formation --> Bone spurs can push on the nerve roots

Term
Lumbar Spondylosis
Definition

- Chronic mechanical back injury

- Pain worsens with activity and at the end of the day

- Relieved by lying supine

- Unilateral or bilateral presentation

- Leg pain possible

- Risk factors: Sex, age, smoking, obesity, occupation, and psychological effect

Term
Complications of Spondylosis
Definition

1. Synovial cyst

2. Spondylolishtesis: Degenerative or isthmic --> Vertebral subluxation of two vertebral bodies

3. Scoliosis: Lateral curvature of the spine

- Idiopathic

- Degenerative

- Congenital, neuropathic, and functional

4. Spinal stenosis: Vertebral fusion of the spine over time

- Pain is worse when walking vs standing

- Relief with bending

- Neurogenic claudication --> Variable but possible, progression moves proximal to distal --> Relieved by sitting

Term
Differential for Chronic Low Back Pain
Definition

- Mechanical --> Relieved by rest

- Systemic polyarthritis: acute muscle spasm >1 hour, back pain relieved with activity and often involving other joints

- Visceral: GI, GU, and Aorta

- Tumors: Insidious, progressive pain --> Worse at night, often with weight loss and >50 years old

- Fibromyalgia: Generalized constant pain unrelated to time of day, position, or activity --> Sleep disturbance, etc

Term
Ankylosing Spondylitis
Definition

- GI involvement: Colitis, ileitis, colonic tumors

- GU involvement: Kidney, prostate, uterus and ovaries

- Aortic aneurysm

- 14.7 x more risk for cancer

Term
Pain Location and Diagnosis
Definition

- Low back pain --> Spine, SI joint, visceral pain, or short leg related pain

- Lateral hip pain --> Referred from spine, SI, greater trochanter, or tensor fascia lata

- Groin pain --> Hip joint, iliopectineal bursa, referred from spine, hernia, and adeopathy

- Lower extremity pain --> Sciatica, referred pain, and vascular insufficiency

Term
Position of Pain and Diagnosis
Definition

- Worse when sitting --> Degenerative Disc Disease

- Worse while standing --> Facet joint or listhesis

- Worse while walking --> Spinal stenosis, scoliosis, trochancteric bursitis, and hip joint

- Worse while walking up stairs --> SI joint

- Produced by valsalva maneuver --> Radiculopathy

Term
Step Off Test
Definition

- Tests for listhesis or subluxation

- Palpate the spinous processes of each vertebra down the spine

- Impression or divet will be felt if listhesis is present

Term
Flank Crease Test
Definition

- Due to scoliosis --> Thoracic or lumbar

- Pelvis on side of curve raises

- Flank crease appeares on the side of the curve

Term
Spinal Flexion Tests
Definition

1. Shober's test

- Find dimple of Venus --> Measure 10 cm above and below and mark

- Have patient bend over and touch toes

- Mark how much the dimple moves --> Should be >5 cm

2. Fingers to floor test

- Patient should be able to reach within 10 cm off the ground

3. Lateral flexion --> Should be 10% of height

4. Hyperextension

Term
Tests for Back Pain
Definition

- Straight leg raise --> Raise leg 30-60 degrees --> If pain between this range, then pain is disc related

- Femoral stretch --> Patient supine, extend hip and flex knee --> Pain means disc problem

- FABER/Patrick Test: Have patient form the number 4 with their legs --> Pain in lower back or lateral hip --> SI joint or lumbar disease

Term
Sacroiliac Joint Pain
Definition

- Transmits forces from the spine to the lower extremity

- Causes butt and lateral hip pain

- Pain increases with asymetrical loading on affected side

- Present in ankylosing spondylitis and osteoarthritis

- Provocation tests: FABER, POSH and REAB test, Gaenslen test, SI tenderness, lateral pressure, and sacral thrust

Term
SI Joint Tests
Definition

- POSH test: Flex knee, place right hand under glut, hold on to shin and push down to illicit pain

- Gaenslen test: Have pt flex one knee while hanging and extending other hip off the edge of table to illicit pain

- Lateral compression: Have patient lie on side and compress hip

- Ilial distraction: Press down on lateral hips to illicit pain

- Range of Motion testing: IR >35, ABD 45, FL 115, and ER >45

Term
Imaging Low Back Pain
Definition

- No imaging early --> Low yield and confusing results

- Reasons not to image

1. Worsening pain

2. Pain > 1 month

3. Objective radiculopathy

- Consider red flags: Cancer, visceral pain, infection, spondylitis, and osteoporosis/fracture

Term
Seronegative Spondyloarthropathies
Definition

- RF-

- Ankylosing spondylitis

- Psoriatic arthritis

- Reactive arthritis/ Reiter's Syndrome

- Spondyloarthropathy associated with IBD

- Undifferentiated spondyloarthritis

- Axial SpA: Predominantly axial involvement

- Peripheral SpA: Predominantly peripheral disease

Term
Extra-articular Manifestations of Seronegative Spondyloarthropathies
Definition

- Eyes: Uveitis and conjunctivitis

- Nose/mouth: Ulcers

- Chest: Interstitial fibrosis --> Primarily in AS

- Cardiac: Aortic abnormalities

- IBD

- Musculoskeletal: Enthesitis and osteopenia

- Skin: Psoriasis, pyoderma gangrenosum, erythema nodosum, and dactylitis

- Neuro: Deficits related to spinal disease

- Renal: Amyloidosis or IgA nephropathy in late disease

Term
Inflammatory Enthesitis
Definition

- Periosteal new bone formation

- Subchondral bone inflammation and resorption

- Bony spurs

- Common sites: Achilles tendon, plantar fascia, patellar tendon, superior and inferior patella, and ischial tuberosity

Term
Classification of Axial Spondyloarthropathies
Definition

1. Sacroiliitis on imaging plus 1 SpA feature

2. HLA-B27 plus >2 SpA features

- SpA features --> Inflammatory back pain, arthritis, enthesis, uveitis, dactylitis, psoriasis, Chron's/Ulcerative colitis, good response to NSAIDs, FHx of SpA, HLA-B27, and elevated CRP

- Sacroiliitis on imaging: Active inflammation on MRI or definite radiographic sacroiliitis

Term
Classification of Peripheral Spondyloarthropathies
Definition

- Arthritis or enthesitis or dactylitis

- Psoriasis

- Inflammatory bowel disease

- Preceding infection

- HLA-B27

- Uveitis

- Sacroiliitis on imaging

Term
Ankylosing Spondylitis (AS)
Definition

- Chronic, systemic inflammatory disorder of the axial skeleton

- Affects the sacroiliac joints and the spine

- Can affect the peripheral joints (hips and small joints)

- Presents around mid 20's 

- 2x more common in men --> 30-900 per 100,000

- HLA-B27 --> 90-95% of AS patients are positive

- 5-10% of Caucasians are HLA-B27+

Term
Clinical Features of AS
Definition

Inflammatory back pain with sacroiliitis and inflammation at other axial skeleton sites

- Peripheral arthritis

- Enthesitis

- Anterior uveitis --> Usually unilateral

- Conjunctivitis in reactive spondyloarthropathy

Term
Articular Manifestations of AS
Definition

- Osteoproliferative --> Bone formation not osteodestruction

- Erosion then fusion of joints

- Spinal changes: Squaring, syndesmophyte, and shiny corners

- Inflammation: Sacroiliitis, spondylitis, and spondylodiscitis

- New bone formation --> Syndesmophytes and ankylosis

- Osteoporosis

- Peripheral arthritis: Mono or oligoarticular, predominantly in LE --> Hip and shoulder affected in ~20%

Term
Clinical Assessment of AS
Definition

- Assess pain, stiffness, and function

- Clinical measures: Tragus/occiput to wall, lumbar flexion (modified Schober and finger-to-floor), cervical rotation, lumbar side flexion, chest expansion, and intermalleolar distance

- Occiput-to-wall: normal is 0 cm

- Chest expansion: >5 cm is normal

- Intermalleolar distance: >100 cm is normal

Term
HLA-B27
Definition

- 70% in reactive arthritis

- 60-70% in spondylitic PsA

- 50-60% in spondylitis with IBD

Term
Pathogenic Role of HLA-B27 in Spondyloarthropathies
Definition

- HLA-B27 participates in antigen presentation --> Binds unique antigenic peptides in its groove

- Formation of heavy chain monodimers and misfolding B27 protein

- Accumulation of B27 within ER --> Pro-inflammatory stress response

- HLA-B27 on cell surface --> Binding to immunomodulatory receptors --> TNF-a release

- Alteration of intracellular invasion/killing of microbes --> Susceptible to Salmonella, Shigella, and Chlaymida infections

Term
Pathogenic Role of Bacteria in Spondyloarthropathies
Definition

1. Reactive Arthritis

- GU or GI infections precipitate reaction

- Persistence of microbial antigens in synovium

2. Gut flora interaction with B27??

- 55% of HLA-B27+ patients with Crohn's develop Ank. spond

- 2.5% of HLA-B27- patients with Crohn's develop Ank. spond

3. HLA-B27+ rats: Germ-free environment --> No disease

Term
Management of Ankylosing Spondylitis
Definition

- No cure --> Symptom control, prevent damage and bone fusion, etc

- Education

- Exercise and physiotherapy regimens

- 1st line: NSAIDs --> new trial of >2 NSAIDs over 4 weeks

- 2nd line: Anti-TNF --> Axial SpA without DMARDs

- Peripheral SpA --> Local glucocorticoid injection and DMARDs

Term
Psoriatic Arthritis (PsA)
Definition

- Prevalence is similar to RA

- 1:1 male: female prevalence

- Often HLA-B27+ also

- ~20-30% of psoriasis patients will develop PsA --> Can occur without obvious rash so check umbilicus, scalp, behind ears, and gluteal folds

- Skin disease predates in 60% but arthritis predates skin disease in 20%

- HLA-Cw6 is associated with skin disease with NO arthritis or nail disease

- Transient and migrating swelling and redness

Term
Assessment of PsA
Definition

- Determine patterns of peripheral arthritis --> Polyarticular and symmetric, oligoarthritic, DIP joints, ray of hand, and arthritis mutilans (telescoping digit)

- Examine skin and nails

- Determine if axial disease is present --> Spinal flexion tests

- Check for enthesitis and dactylitis

- Axial disease can be confused with AS with no visible rash and no other or minimal other joint involvement

Term
PsA Pathogenesis
Definition

- More similar to autoinflammatory conditions driven by the innate immune system

- Osteodestructive disease

- Skin lesions in intergluteal regions and scalp with nail lesions

- Post-streptococcal psoriasis can evolve into chronic psoriasis in 40% of cases

- Link between trauma and subsequent PsA of the same digit

- Subclinical enthesitis and osteitis is common at sites of PsA

Term
DMARDs for Skin and Peripheral PsA
Definition

- Skin --> Same for psoriasis

- Joints --> Methotrexate

- Combination of MTX and anti-TNF

- Leflunamide is effective too

- Sulfasalazine has been studied

Term
Biologics for PsA Treatment
Definition

1. TNF inhibitors --> Infliximab and etanercept

- Effective for arthritis, structural damage, skin, enthesitis, dactylitis, and nail involvement

2. Alefacept

3. Abatacept: CTLA4-Ig

4. Ustekinumab: IL-12/IL-23 inhibitor

5. Rituximab: CD20 antagonist --> Depletes B-cells

6. Apremilast: Oral PDE-4 Inhibitor

7. Tocilizumab: IL-6 receptor inhibitor

Term
Reactive Arthritis
Definition

- Aseptic peripheral arthritis

- One or more extra-articular manifestations

- Following certain GU or GI infections

- 9x more common in men for venereally acquired GU infections

- Equal prevalence for enteric infections

- Common in younger patients --> 30-40/100,000

- Disease course: Ave. duration 4-5 months but some have mild persistent symptoms for 1 year

Term
Bacterial Triggers of Reactive Arthritis
Definition

- Chlamydia trachomatis

- Shigella flexneri

- Salmonella spp.

- Yersinia enterocolitica

- Y. pseudotuberculosis

- Campylobacter fetus jejuni

- Clostridium difficile

- Chlamydia pneumonia

Term
Presentation of Reactive Arthritis
Definition

- NGU/persistent diarrhea is usually the first presentation

- Conjunctivitis follows several days later

- Articular features usually appear last

- Arthritis: Additive, asymmetrical, oligoarticular, and usually of the lower limbs

- Classic triad: Conjunctivitis, urethritis, and arthritis

- 25% of cases with unknown triggering organism

- Chronic when >6 months

Term
Clinical Manifestation of Reactive Arthritis
Definition

1. Articular manifestations

- Arthritis

- Enthesitis

- Tenosynovitis

- Low back pain

- Dactylitis (Sausage digits)

2. Non-articular manifestations

- Mucocutaneous: Keratoderma blennorhagica, circinate balantitis, stomatitis, and nail changes

- Aortitis

- Amyloidosis

- Uveitis

- Constitutional symptoms

Term
Diagnosis of Reactive Arthritis
Definition

- Lab findings: Anemia, leukocytosis, thrombocytosis, ESR, HLA-B27 (70-80%), bacterial cultures, and HIV test

- Radiography: Periosteal reaction and erosion at entheses

Term
Treatment of Reactive Arthritis
Definition

- NSAIDs

- Corticosteroids

- Sulphasalazine

- Methotrexate (no good data though)

- Antibiotics for infection if preceeded by infection --> Depends on the preceeding infection

Term
IBD-Associated Spondyloarthropathy
Definition

- Associated with Crohn's or UC

- 10-50% of IBD patients have peripheral arthritis

- Asymetrical oligoarthritis of lower limbs

- Acute and remitting: Pauciarticular and flares with IBD

- Chronic/frequent relapses: Polyarticular and may be migratory

- Rule out infectious etiology

- Increased prevalence in males

- Extra-articular features --> Erythema nodosum and pyoderma gangrenosum

- Treatment: NSAIDs, steroids, sulfasalazine, and biologics

Term
Amyloidosis
Definition

- Pathologic proteinaceous substance deposited cells in various tissues and organs of the body in a wide variety of clinical settings

- B-pleated sheet amyloid proteins --> Congo red molecules

- Tissue deposition: Myocardium, kidney, and any other organ involvement

- Classification: Localized vs. generalized, primary vs. secondary, and major fibril protein involved

Term
Amyloid
Definition

- Presence of protein deposits

- Protein deposits: Fibrillar ultrastructure, Congo red staining with green birefringence, and crossed B-pleated sheet

- Composition: Protein fibrils, P-component and proteoglycans

- P-component: Alpha-1 glycoprotein, normal serum component and doughnut shaped pentagonal structure on EM

- Transthyretin: Transports thyroxine and retinol --> Senile cardiac amyloid

- B2-microglobulin: Component of MHCI molecules --> presents in long term dialysis patients

- B2 Amyloid protein: A4 peptide --> Presents in Alzheimer's Disease

- Pro-calcitonin, proinsulin, and keratin amyloid

Term
AL/Primary Amyloid
Definition

- Amyloid of immune origin

- Plasma cell dyscrasia --> Fibril produced by monoclonal plasma cells

- Fibril: Whole or fragments of Ig light chains

- Light chain proteins of variable length --> 5,000-25,000 daltons

- More likely associated with lambda light chains (75%) and 25% with kappa light chains

- Light chains deposit in various tissues leading to organ dysfunction

- 20% associated with multiple myeloma

Term
AA/Secondary Amyloidosis
Definition

- SAA (acute phase protein) due to inflammatory liver conditions

- Increased chronic inflammation and some tumors

- Incomplete cleavage of SAA gives rise to insoluble AA intermediates

Term
AF/Fibril Amyloidosis
Definition

- Deposition of transthyretin (prealbumin) --> TTR

- Transthyretin: Serum carrier protein for thyroid hormones and vitamin A

Term
Symptoms and Presentation of AL Amyloid
Definition

- Symptoms: Fatigue, weight loss, CHF symptoms, nephrotic syndrome, malabsorption and neuropathy

- Physical Exam: Hepatomegaly (30%), purpura, edema, macroglossia (20%), enlarged spleen and nodes are less common

- Kidney: Glomerular deposits, renal tubules, and blood vessels --> Thickening of mesangial matrix early and obliteration of capillary lumina and glomeruli late

- Spleen: Deposits limited to white pulp (sago spleen) or extensive involvement of red and white pulp (lardaceous spleen)

- Liver: Deposits in the space of Disse early and total replacement of liver parenchyma late

- Heart: Restrictive cardiomyopathy

- Tongue: Macroglossia

- GI: Amyloid infiltration leading to dysmotility and malabsorption

Term
Diagnosis of Amyloidosis
Definition

- Abdominal fat pad aspirate --> Easiest to obtain

- Gingival or rectal biopsies

- Visceral organ biopsies --> Not the first choice

- Serum/urine electrophoresis and immunoelectrophoresis

- Bone marrow biopsy --> Amyloid deposits

- Congo red stain with apple green biorefringence

Term
Convential vs. New Treatment of AL
Definition

- Oral cyclic melphalan and prednisone

- Median survival of 16-18 months

- Hematologic complete response is rare

- Reversal of present organ dysfunction is also rare

- Stops progression of disease

- High-dose melphalan with stem cell transplant --> Median survival of 73 months and a 55% 5 year survival rate

Term
Types of Autoimmune Diseases
Definition

1. Localized: T-cells and autoantibodies directed against a single cell type or organ

- Hashimoto thyroiditis

- Autoimmune atrophic gastritis

- Autoimmune hemolytic anemia

2. Systemic: Autoimmune reaction directed against a broad array of antigens

- Systemic lupus erythematosus (SLE)

- Sjogren's syndrome

- Systemic sclerosis

- Rheumatoid arthritis

Term
Antinuclear Antibodies (ANA)
Definition

- Four general categories: Antibodies to DNA, histones, non-histone proteins bound to RNA, and nucleolar antigens

- Homogenous: Generic binding to chromatin, histones, and DNA --> Non-specific

- Speckled: Binding to non-DNA components

- Nucleolar: Nucleolar RNA binding --> Diffuse scleroderma

- Centromere: Limited scleroderma (CREST syndrome)

Term
Pathology of Sjogren's Syndrome
Definition

- Sicca syndrome: Dry eyes, dry mouth, etc

- Lymphocytic infiltration and fibrosis of the lacrimal/salivary glands

- CD4+ helper T-cell infiltration along with B-cells and plasma cells

- Acini are initially destructed by lymphocytes

- Duct involvement late in progression of disease

- Lung disease: Interstitial B-cell involvement and nodule formation --> Fibrosis late in disease

- ANA IF pattern: Speckled

Term
Pathology of Systemic Sclerosis (Scleroderma)
Definition

- 3x more common in women

- Excessive fibrosis throughout the body

- Skin is most affected but GI tract, kidneys, heart, muscle and lungs are involved

- T-cells elaborate cytokines stmulating fibroblasts to produced collagen

- Endothelial cell injury? --> Granzyme A exposure --> Intimal fibrosis and platelet activation

- Skin pathology: Perivascular lymphocytes (CD4+), edema, swelling and degeneration of collagen, thickening and occlusion of small dermal BVs, thinning of epidermis, loss of rete pegs, and atrophy of dermal appendages

- GI pathology (90%): Collagenous replacement of muscularis especially in the esophagus --> Stricture formation, dysmotility, and loss of villi

- Kidney pathology: Fibrosis of BV walls --> Hypertension and renal failure

- Lungs: ILD and PAH

- Heart: Pericarditis and myocardial fibrosis

- ANA IF pattern: Nucleolar --> Anti-topoisomerase (Anti-Scl-70) in diffuse and anti-centromere in LcSSc

Term
Pathology of Rheumatoid Arthritis
Definition

- Immune complex deposition of RF and IgG antibodies

- Complexes form in sera, synovial fluid, and synovial membranes

- Extra-articular manifestations due to immune complex circulation

- Rheumatoid nodules: Fibrinoid necrosis of collagen surrounded by inflammatory cells

- Blood vessels: Vasculitis with  tissue infarction

1. Synovial infiltration of CD+ T-cells, plasma cells, and macrophages

2. Synovial hyperplasia, edema, thickening, increased vascularity, and fibrin deposition results

3. Fibrovascular mass or pannus grows over the articular cartilage and erodes it --> Destroys the joint

 

Term
Differential of Myopathy
Definition

- Idiopathic inflammatory myositis

- CTD-associated myositis

- Endocrine

- Infections --> Viral, bacterial and trichinosis

- Metabolic/electrolyte

- Neurolgic --> ALS, myasthenia gravis, Eaton-Lambert, Guillan-Barre, and muscular dystrophies

- Toxin/Drugs

- Storage diseases

- Other inherited conditions

Term
Dermatomyositis
Definition

- Progressive condition

- Symmetrical proximal muscle weakness with elevated muscle enzyme levels --> Can lead to dysphagia, a hoarse voice, neck weakness and respiratory problems

- No distal muscle involvement

- Skin rash often involved but can be very subtle --> Often precedes weakness

- Myalgias in 25% of cases

- Higher risk of malignancy --> Lung, colon, stomach, ovarian, and breast cancer

Term
Dermatomyositis Rash Presentations
Definition

1. Gottron's sign: Erythematous/violaceous, scaly rash on the MCP, PIP and DIP joints

2. Gottron's Papules: Pink papules and scale over the PIP and MCP joints and extensor surfaces of the elbows

3. Heliotrope Rash: Lavender eruption of the upper eyelids with eyelid swelling

4. Shawl Sign and V-Sign: Diffuse, flat pink/red lesion occuring over the chest (v-sign) and shoulders (shawl)

- Exacerbated by UV light --> Associated with anti-Mi2 antibodies

5. Erythroderma: Red skin, possibly resembles the shawl sign but possible in other cutaneous areas

6. Mechanic's Hands: Palms and fingers appear rough and cracked with "dirty-appearing" lines --> Anti-synthetase syndrome

- Either DM or PM

7. Flagellate Erythema: Linear, violaceous streaks on the trunk

8. Calcinosis cutis: Calcium deposition within the skin

- Unusual in adult DM --> Juvenile DM

9. Periungual changes: Capillary dilation

Term
Polymyositis
Definition

- Proximal muscle weakness

- Can be associated with mechanic's hands finding

- Other rash findings are uncommon

- Myalgias present in 25%

- Lung disease: Diaphragm or intercostal muscle involvement or ILD (10%)

- Highest rates of ILD with anti-synthetase syndrome (Anti-Jo-1 antibodies)

- Anti-SRP antibodies more common than in DM

- Pathology: Intra-fascicular cellular infiltrate of CD8+ T-cells --> Abnormal muscle fibers are scattered throughout the fascicle

Term
Pathology of Dermatomyositis
Definition

- Muscle fiber necrosis

- Perifascicular distribution of inflammation

- Complement (C5-C9) deposits in vessel walls

- Cytotoxic lymphocytes (CD4+)

- Perivascular inflammation

Term
Diagnosis of Dermatomyositis
Definition

- Elevated CK, aldolase, AST/ALT, and lactate dehydrogenase (LD)

- Abnormal electromyogram --> Decreased muscle action potential amplitude, short duration, increased insertional action, fibrillations, and complex repetitive discharges

- MRI usueful to identify location for biopsy

- Biopsy necessary to diagnose

Term
Amylopathic Dermatomyositis
Definition

- Rash, auto-antibodies, and even muscle biopsy signs of DM

- No muscle weakness

- Usually develop full blown DM later in life

Term
Anti-Synthetase Syndrome
Definition

- Presenatation: Fever, non-erosive polyarthritis, Mechanic's Hands, Raynaud's Syndrome, and ILD

- ILD --> Anti-Jo-1 antibody --> Histidyl-tRNA synthetase antibody

- Unknown if this antibody actually has to do with pathogenesis 

Term
Drug-Induced Muscle Damage/Myopathy
Definition

- Colchicine

- Statins

- Hydroxychloroquine/Plaquinil and other anti-malarials

- Zidovudine

- Alcohol

- Cocaine

- Corticosteroids --> No CK elevation

- AZT

- Heroin

- Amiodarone

Term
Inclusion Body Myositis
Definition

- Previously considered a form of polymyositis

- Presents in an older age group and more common in men

- Weakness and atrophy generally of both proximal and distal muscles --> Hand flexors and quads most affected

- Gradual onset of weakness

- Very resistant to treatment, even IVIG

- Lower CK elevation

- No autoantibodies associated --> May be ANA+

- Pathology: CD8+ T-cell infiltrate with red-rimmed vacuoles contain B-amyloid --> Fatty infiltration and atrophy also present

Term
Muscle Damage Definitions
Definition

- Myopathy: Abnormal condition/disease involving the muscle

- Myositis: Inflammation of muscle

- Myalgias: Muscle pain

- Polymyalgia: Pain in several muscle groups

Term
Anti-SRP Syndrome
Definition

- Prominent Cardiac Involvement

- Distal muscle weakness may be present but still uncommon!!

- Resistant to therapy

- More similar to PM than DM

Term
Viral Myositis
Definition

- Echovirus, coxsackie virus, influenza A and B, parainfluenza, HIV, and others

- Biopsy: Normal or show muscle necrosis without typical inflammatory characteristics of DM or PM

- HIV-associated: EMG and biopsy findings similar to PM --> Treated with HAART therapy or corticosteroids

Term
Myopathies with Normal CPK Levels
Definition

1. Corticosteroid Induced Myopathy: EMG and biopsy findings are normal

2. Myasthenia Gravis: Antibodies to ACh receptors --> Muscle fatiguability and diffuse weakness

3. Musclar dystrophy and myotonic dystrophy: Inherited muscle disorders --> Prominent endomysial inflammatory cell infiltrates

4. Inherited Metabolic Myopathies: Disorders of carbohydrate and lipid metabolism --> intermittent episodes of acute muscle pain and tenderness on exertion

- Myoblobinuria and red/brown urine

- Can develop chronic weakness

Term
Hypothyroidism and Myositis
Definition

- Severe hypothyroidism

- Leads to weakness and elevated CPK

- Inflammatory changes are less severe

- Muscle biopsy: Non-specific or normal

Term
Fibromyalgia
Definition

- Chronic, widespread musculoskeletal pain syndrome

- Affects 2% of the population

- Associated symptoms: Fatigue, sleep disturbance, migraine, IBS, neuropathic symptoms, and mood problems

- No objective diagnostic tests or pathologic findings

Term
Pathogenesis of Fibromyalgia
Definition

- Unknown --> Theories include aberrant CNS functioning and hypersensitivity to stimuli that otherwise shouldn't cause pain

- Pain on both sides of the body, above and below the waist, and axial skeletal pain must be present

- 11/18 tender points must be present

- Must rule out other diseases before diagnosis

Term
Treatment of Fibromyalgia
Definition

- Education

- CBT, aerobic exercise, and sleep hygiene procedures

- Tricyclic antidepressants

- Pregabalin/Gabapentin

- Do NOT use opioids

Term
Vasculitis
Definition

- Rare diseases involving inflammation of blood vessels with resulting ischemia of tissues

- Inflammatory infiltrate of vessel wall

- Fibrinoid necrosis

- Extravasation of RBCs into connective tissue

- Strange diseases with wildly varied presentations

- Diagnostic delays

- Life and organ-threatening disease --> Can involve any organ

Term
Suspecting Vasculitis
Definition

- Unexplained prolonged constitutional illness

- Multi-system organ disease

- Recurrent upper respiratory disease

- Pulmonary-renal syndrome

- Peripheral vascular examination abnormalities

- Palpable purpura

- Inflammatory eye disease

Term
Diagnosis of Vasculitis
Definition

- Combination of clinical, serological, and pathological evidence

- Always need biopsy of tissue to diagnose

- Angiography can sometimes substitute for tissue

Term
Treatment of Vasculitis
Definition

- Glucocorticoids

- Cytotoxic/Immunosuppressive agents --> Cyclophosphamide , azothiaprine, and methotrexate

- Biologic agents --> Anti-TNF-a and Rituximab (B-cell depletion)

- Surgery for ischemia

- Anticoagulation

Term
Small Vessel Vasculitis
Definition

- Granulomatosis with polyangiitis (Wegner's): ANCA

- Microscopic polyangiitis: ANCA

- Churg-Strauss Syndrome: ANCA

- Cryoglobulinemic vasculitis

- CTD-associated vasculitis

- Henoch-Schonlein pupura

- Drug-induced vasculitis

- Primary angiitis of CNS

- Lymphomatoid granulomatous

Term
Presentation of Small Vessel Vasculitis
Definition

- Involvement of arterioles, capillaries and venules

- Purpura

- Scleritis

- Glomerulonephritis

- Alveolar hemorrhage

Term
Medium Vessel Vasculitis
Definition

- Behcet's Disease

- Polyarteritis nodosa --> Aneurysms of arcuate renal arteries

- Kawasaki Disease --> Coronary aneurysm

- Thromboangiitis obliterans

Term
Large Vessel Vasculitis
Definition

- Takayasu's Arteritis

- Giant Cell Arteritis

- Relapsing Polychondritis

- Cogan's Syndrome

- Isolated aortitis

- Presents with stenosis, occlusion and aneurysms

Term
ANCA-Associated Vasculitis
Definition

- Small vessel vasculitis

- Differential: Granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), and Churg-Strauss Syndrome (CSS)

Term
Diagnosis of ANCA-Associated Vasculitis
Definition

- Immunoflourescence: C,P, and A patterns --> Non-specific

- Antigen-specific ELISA: Proteinase 3 (PR3) or myeloperoxidase (MPO) are diagnostic

- Granulomatosis with polyangiitis (GPA): 90% cANCA/PR3 and pANCA/MPO

- Microscopic polyangiitis (MPA): 70% pANCA/MPO

- Churg-Strauss Syndrome (CSS): 40-50% pANCA/MPO

Term
Granulomatosis with Polyangiitis (GPA)
Definition

- Upper airway disease: Nasal septum, sinuses, and subglottic stenosis

- Pulmonary disease: Nodules and alveolitis

- Glomerulonephritis

- Neuropathy

- Arthritis/arthralgias

- Malaise/fatigue

- Eye disease --> Scleritis/episcleritis and pseudotumor

- Skin/mucosa --> Purpura, nodules and oral ulcers

- Vascular --> Gangrene

- Cardiac disease

- GI disease

- Labs: ANCA and hematuria/proteinuria

- Pathology: Granulomas and vasculitis features

Term
Clinical Manifestations of GPA
Definition

- CXR: Pulmonary nodules

- LM: Pauci-immune GN

- Begins in airways --> Sinonasal disease (75% at presentation and 90% overall)

- Epistaxis, crusting, and rhinitis --> Recurrent sinus infections

Term
Churg-Strauss Syndrome
Definition

- Tissue eosinophilia, extra-vascular granuloma and necrotizing vasculitis

- Primary vasculitis with associated eosinophilia

- Asthma and allergies --> Hypereosinophilia --> Vasculitis

Term
Presentation of Churg-Strauss Syndrome
Definition

1. Prodromal phase

- Asthma --> Constant in (96-100%), latency of months/years, and severe and difficult to control

2. Hypereosinophilia

- Blood eosinophilia (100%) and lung infiltrate (27-72%)

3. Vasculitic Phase

- General symptoms, peripheral neuropathy, purpura, heart involvement, GI symptoms, arthralgia, myositis, and glomerulonephritis

Term
Takayasu's Arteritis
Definition

- Large vessel vasculitis --> Arterial stenoses, narrowing and occasional aneurysm formation

- 80-90% of patients female --> <40 years old

- Chronic and relapsing course 

- Mimics: Atherosclerosis, fibromuscular dysplasia, and congenital vascular abnormalities

- Presentation: Light-headedness, stroke, and severe hypertension (renal stenosis)

Term
Diagnosis and Treatment of Takayasu's Arteritis
Definition

- Diagnosis: Combining physical examination with angiographic evidence

- Treatment: Required high-dose glucocorticoids plus additional immunosuppressive agents

Term
Giant Cell/Temporal Arteritis
Definition

- Most common vasculitis --> Affects medium sized cranial arteries

- Classification: >50 years old, elevated ESR, temporal artery abnormality, new onset headache, and abnormal artery biopsy

- Symptoms: Jaw claudication (45%), headache (68%), vision loss (14-16%), other CNS problems (15%), tongue claudication (6%), peripheal extremity claudication (4%), and Raynaud's phenomenon (3%)

- Musculoskeletal Manifestations: Polymyalgia rheumatica (39%), Non-PMR MS symptoms (30%), and synovitis (15%)

- General symptoms: Fever, malaise, and arthralgias

- Diagnosis: Vasculitis of temporal artery, elevated acute phase reactions, anemia, and thrombocytosis

- Treatment: High-dose glucocorticoids and option use of immunosuppressive agents

Term
Polymyalgia Rheumatica (PMR)
Definition

- Elderly onset --> Typically presents with bilateral shoulder weakness

- Profound arthralgias and muscle weakness

- Shoulder and hip girdles, severe morning stiffness, and no true muscle weakness or myositis

- ESR >40 and often >100

- Treatment: Steroids --> VERY responsive

- Must be present to diagnose GCA

- Not a true vasculitis but highly associated with GCA

- 30% of patients will develop GCA --> Ask about jaw claudication, vision abnormalities, etc

Term
Polyarteritis Nodosa (PAN)
Definition

- Middle-vessel vasculitis

- Recently has become rarer due to decreased prevalence of HBV infection due to vaccines

- Involved organs: Nerves, skin, intestines, and others

- Manifestations: Intestinal ischemia, renal artery and renal parencymal involvement with microaneurisms, mononeuritis and skin lesions

- Types: Hepatitis-associated (HBV) PAN and idiopathic PAN --> Lower association with HCV

- Diagnosis: Clinical findings and angiographic testing

- Treatment: High-dose glucocorticoids

Term
Criteria for PAN Diagnosis
Definition

- Weight loss of >4 kg

- Livedo reticularis: Mottled reticular pattern over the skin of the extremities or torso

- Testicular pain or tenderness

- Myalgias, weakness, or leg tenderness

- Mononeuropathy or polyneuropathy

- Diastolic BP >90 mmHg

- Elevated BUN and Cr

- HBV infection

- Arteriographic abnormality

- Biopsy of small vessel showing vasculitis

Term
Behcet's Disease
Definition

- Medium vessel vasculitis

- Highest prevalence in populations surrounding the Mediterranean Sea --> Turkish population

- Treatment: Glucocorticoids and immunosuppressive theray

- Presentation: Painful oral or genital ulcers, ocular inflammation, skin lesions, arthralgias, and vasculitis of both arterial AND venous systems

- Skin lesions: Erythema nodosum, pseudofolliculitis, papulopustular lesions, and acneiform nodules

- Eye manifestations: Uveitis or retinal vasculitis --> Can lead to blindness

Term
Microscopic Polyangiitis (MPA)
Definition

- ANCA-Associated vasculitis

- Small vessel disease

- Predilection for rapidly progressive glomerulonephritis and alveolar hemorrhage

- Neuropathy is common

- Skin lesions also common

- Diagnosis: Combination of clinical findings, ANCA testings, and pathologic specimens (biopsy)

- Treatment: High-dose glucocorticoids with immunosuppressive therapy

Term
Drug-Induced Vasculitis
Definition

- Almost every class of medication has been associated with vasculitis

- Some drugs can result in ANCA-associated vasculitis

- Most common form seen

- Often self-limited to skin

- Very serious systemic forms are possible

Term
Scleroderma/Systemic Sclerosis
Definition

- Localized --> Morphea and linear scleroderma

- Systemic Sclerosis: Limited, diffuse, and sine scleroderma

Term
Limited Cutaneous Systemic Sclerosis (LcSSc)
Definition

- Formerly known as CREST --> Calcinosis, Raynaud's, Esophageal dysmotility, Sclerodactyly, and telangiectasias

- Involvement of acral skin --> Below elbows and knees and face

- Raynaud's phenomenon may preceed skin thickening by years

- Pulmonary HTN and ILD are most common systemic symptoms

- Anti-centromere antibodies --> 80-90%

- Nailfold capillaroscopy --> Dilated capillary loops

Term
Diffuse Cutaneous Systemic Sclerosis (DcSSc)
Definition

- Widespread skin thickening with early involvement of internal organs --> Progressive for the first 3 years

- Raynaud's phenomenon common too

- Anti-topoisomerase antibody (Anti-Scl-70)

- Nailfold capilaroscopy --> Capillary dilation and dropout

Term
Epidemiology of Scleroderma
Definition

- 75,000-100,000 cases in the US --> 20/1,000,000 new cases per year

- 4x more common in females --> 30-50 year olds

- Severe phenotype in young black women

Term
Clinical Features of SSc
Definition

- Raynaud's phenomenon

- Skin thickening and joint tightening

- GI dysmotility, stricture formation and malabsorption due to loss of villi

- Cardiovascular --> Pericarditis

- Pulmonary hypertension and ILD 

- Renal arterial stenosis

- Systemic features

- Myositis and arthritis

Term
Pathogenesis of SSc
Definition

- Immune dysregulation --> Specific autoantibodies, Th2 cells and B-cells

- Vascular abnormalities due to endothelial and vascular smooth muscle abnormalities --> ET-1, VCAM-1, and ECAM-1

- Fibrotic features due to myofibroblasts

- Immune cell activation, localization and vascular injury and proliferation

- Cytokines: IL-4, IL-13, CTGF, TGF-b, and PDGF

- TGF-b: Pro-fibrotic in SSc --> Binds receptors and activates SMADs

- TGF-b can produce many different responses depending on the other cytokines present

- PDGF: Overexpression in myocardium and lungs with pulmonary fibrosis

- Possible autoantibodies to PDGF receptor??

- Pro-fibrotic pathway via c-Abelson (c-Abl) Tyrosine Kinase --> Non-SMAD pathway

Term
Treatment for SSc
Definition

- Gleevac (Imatinib): Blocks intracellalar c-Abl --> Prevents dermal and pulmonary fibrosis --> Dual inhibitor of TGF-b and PDGF receptor pathways

- Ischemic digits: Prostanoids, sildenafil/revatio, sympathectomy, intraarterial vasodilatory, antibiotics, and bosentan (ET antagonist)

- PHTN: Ca channel blockers, anticoagulation, aerosolied PGI analogs, subcutaneous PGI analogs, inhaled NO, IV epoprostenol, and bosentan (ET antagonist)

- Autolagous Stem Cell Transplant: Harvest marrow, isolate CD34+ stem cells --> Irradiate marrow --> Inject harvested marrow --> Immune cell "reset"

Term
Vascular Disease in SSc
Definition

- Vasoconstriction --> Catecholamines, endothelin, and angiotensin overproduction with underproduction of NO and PGI

- Tissue damage due to overproduction of oxidation products, endothelin, TGF-b and genetic predisposition --> Leads to matrix proliferation

- Endothelin-1: Binds ET-1 --> Vasoconstriction, SMC proliferation, matrix biosynthesis, myofibroblasts, and inflammation

- Leads to ischemia in Raynaud's, etc

Term
Lung Disease in SSc
Definition

- Leading cause of death in both DcSSc and LcSSc

- 30-40% of DcSSc patients have ILD --> Anti-Scl-70 antibodies

- Primary and secondary PHT --> 5% with severe PHT, 25-50% with mild PHT

- Risk factors: Rapid disease progression, deep tendon friction rubs, pericardial effusion, dyspnea, fatigue, weight loss, elevated ESR, and anemia

- Progression: Alveolitis --> Interstitial fibrosis (NSID) --> "Ground Glass" on HRCT --> Pulmonary fibrosis

Term
Pulmonary Hypertension in SSc
Definition

- Late LcSSc disease --> CREST

- Normal lung exam

- Increased P2 sound

- RV heave

- Normal lung volumes with low DlCO or disproportionately decreased DlCO

Term
Hydroxychloroquine/Plaquinil
Definition

- Anti-malarial drugs --> Disease Modifying (DMARD)

- Unclear mechanism

- Lysosomal accumulation leading to increased permeability leading to pro-apoptotic cascade

- Fibroblast or B-cell effect

- Therapeutic use: Lupus and RA, less effective than other agents, slow onset, and used in combination

- Side effects: Retinopathy possible due to drug accumulation in the retina

- Safe during pregnancy

Term
Sulfasalazine
Definition

- 5-Aminosalicylates --> DMARD

- Unclear --> T or B cell effect?? 

- Inhibits NFkB signaling --> Induces T-cell apoptosis

- Side Effects: Hemolytic anemia (especially in G6PD deficiency), rash, leukopenia, hypersensitivity, and oligospermia

- G6PD: Inadequate production of antioxidant GSH leads to RBC lysis with exposure to oxidizing drugs

- Therapeutic use: RA and spondyloarthropathies

Term
Methotrexate
Definition

- DMARD --> Purine/Pyrimidine Synthesis inhibitor

- Structure very similar to tetrahydrofolic Acid (THF) --> Blocks folic acid by inhibiting IMP synthesis

- Developed to treat cancer

- Lower doses for arthritis --> 1/100th taken once a week

- Administration: Oral and parenteral formulation

- First line therapy as monotherapy or combination therapy

- Side effects: Mucositis, liver damage, and teratogenicity

- Dose adjustment: Renal impairment or concomitant use of OATp inhibitors --> Blocks MTX renal secretion

- Therapeutic Use: Mild to moderate arthritis, myositis, vasculitis, lupus, and SSc

Term
Azathioprine
Definition

- DMARD --> Purine/Pyrimidine Synthesis Inhibitor

- Pro-drug --> 6-mercaptopurine (6-MP) --> Nucleotides

- Converted to nucleotides by HGPRT (salvage pathway)

- Mechanism: Inhibits B and T cell replication by stopping DNA replication and selective initiation of apoptosis of T-cells

- 6-Mp inhibits Rac-1 signaling --> Induction of apoptosis

- Side effects: Bone marrow suppression, infection and malignancy (lymphomas)

- Dose Reduction: Thiopurine methyltransferase (TPMT) deficiency --> TPMT inactivates 6MP

- Therapeutic Use: SLE, myositis, and vasculitis

Term
Leflunomide
Definition

- DMARD --> Purine/pyrimidine synthesis inhibitors

- Converted to active metabolite with VERY long half-life

- Enterohepatic re-circulation --> Enterohepatic circulation

- Inhibits dihydroorotate dehydrogenase

- Inhibits T-cell proliferation and antibody production by B-cells

- Side effects: Dose-dependent diarrhea and elevation of liver enzymes

- Therapeutic use: Rheumatoid arthritis, psoriatic arthritis, and vasculitis

- Loading dose generally not recommended due to extremely long half-life

Term
Mycophenolate
Definition

- DMARD --> Purine/Pyrimidine

- Pro-drug --> Inhibits inosine monophosphate dehydrogenase

- Depletes purine synthesis

- Blocks B and T-cell replication

- Side effects: Gastrointestinal and hematologic toxicities

- Therapeutic use: SLE, vasculitis, and transplant rejection

Term
Cyclophosphamide
Definition

- Biotransformed in the liver by P450 enzymes --> Crosslinking/alkylation of DNA

- Suppression of T-cell function

- Administration: Oral or IV with high hepatic clearance

- Therapeutic use: Vasculitis (with glucocorticoid), SLE, SSc pulmonary fibrosis, malignancies --> NOT for RA

- Side effects: Bone marrow suppression, infertility, infection and alopecia

Term
Glucocorticoids
Definition

- Mechanisms: Multiple anti-inflammatory and immunsuppressant effects --> NF-kB inhibition, blocks transcriptional activity, inhibition of cytokine secretion, and inhibition of T and B-cell replication

- Administration: Short course of PO or intra-articular injection

- Side effects: Cushing's syndrome with long term PO use, osteoporosis, and osteonecrosis

- Therapeutic use: Many inflammatory and autoimmune diseases

Term
TNF-a Antagonists
Definition

- Etanercept: Fusion protein of IgG with extraceullar domain of the TNFa receptor

- Infliximab: Chimeric mouse/human IgG with high affinity for TNFa

- Adalimumab: Fully humanized IgG

- Certolizumab

- Golimumab

- Mechanism: Bind the pro-inflammatory mediator with high affinity and block its interaction with p75 membrane receptors

- Side effects: Infusion reactions, bruising, respiratory and other infections, reactivation of latent TB, aggravation of CHF, increased risk of malignancies (children,) development of auto-antibodies, and lupus-like syndrome

- Therapeutic use: RA, AS, PsA, and IBD

- Contraindications: PPD+ patients --> Reactivation of TB possible

Term
APC/T-cell Co-Stimulation Inhibitors
Definition

- Abatacept --> Fc portion of IgG fused to extracellular binding domain of CTLA-4

- Mechanisms: Binds CTLA4 receptor and inhibits T-cells

- Side effects: Infusion-related reactions, infections, and antagonism of immunizations

- Contraindications: TNF-a antagonist use and recent live vaccine injection

- Do NOT use in combination with TNF-a antagonists

- Therapeutic use: RA

- Along with other DMARDs

- Dosing: 30-min IV injection --> First dose, 2 weeks, 4 weeks, then monthly

- Very expensive --> $20,000 per year

Term
Rituximab
Definition

- Chimeric mouse/human IgG antibody --> Depletes B cells

- Mechanism: Binds CD20+ B cells --> Opsonization and phagocytosis by macrophages or neutrophils

- Approved initially for non-Hodgkins lymphoma treatment

- Side effects: Infusion reactions, development of antibodies, severe mucocutaneous reacitons and reactivation of viral infections

- Pre-treatment with antihistamines and glucocorticoids can reduce infusion reactions

Term
Recommended DMARD Therapy
Definition

- RA: Non-biologics (MTX with or without hydroxychloroquine or sulfasalazine) then biologics with MTX

- AS: NSAIDs then TNFa antagonists

- SLE: NSAIDs, glucocorticoids, and hydroxychloroquine --> MTX/azathioprine, etc, mycophenolate, rituximab, and belimumab as second line agents

Term
Gout
Definition

- Most common inflammatory arthritis in the US

- Inflammatory reaction to uric acid crystals

- Results from hyperuricemia

- Acute gout flare: Episodic arthritis with severe pain and swelling -->Usually in the great toe --> Usually resolves within a couple days

- Chronic tophaceous gout: Chronic deformity and disability due to uric acid crystal deposition --> DIP, PIP, MCP, wrist, ear lobes, etc. 

Term
Prevalence and Development of Gout
Definition

- More common in the elderly

- More common in men than women

- Risk increases exponentially with a serum uric acid level >8 mg/dL

- Uric acid Synthesis: Hypoxanthine --> Xanthine --> uric acid all via xanthine oxidase

- Gout appears in patients who have reduced uric acid excretion or increased uric acid production

- >90% due to decreased excretion

- ~40% of patients with gout have a FHx

Term
Clinical Features of Acute Gout Flare
Definition

- 75% in great toe and monarticular and ~50% of initial attacks

- Begins over hours

- Attacks may be accompanied by fever and other systemic symptoms

- Triggers: Minor joint trauma, alcohol, purine-rich foods, acute medical illness, diuretics, and dehydration --> Most leading to reduced excretion

- Untreated attacks tend to resolve in over a week

Term
Comorbiditis with Gout
Definition

- Metabolic syndrome: 63%

- Hypertension: 74%

- Obesity: 53%

- Type II diabetes: 26%

- Coronary Artery Disease: 25 or 18%

- Chronic kidney disease: 20%

- Kidney stones: 14-15%

Term
Drinks Associated with Gout Flares
Definition

- Alcohol and sugar-sweetened drinks --> Raises uric acid level in serum and increases gout risk

- Alcohol and fructose --> Increases breakdown of intracellular ATP --> Increased uric acid production

- Alcohol --> Dehydration and increased lactic acid levels

- Fructose --> Insulin resistance

- Beer contains large quantities of guanosine --> Purines

- Moonshine can be tainted with lead --> Renal tubular damage and hyperuricemia due to decreased excretion

Term
Diagnosis of Gout
Definition

- Synovial fluid analysis

- Monosodium urate crystals in joint --> Appear yellow with polarized light parallel to crystal --> Negative biorefringence

- Crystals are needle like in shape

- When light is perpendicular --> Blue color

Term
Treatment of Gout
Definition

1. Treatment for Acute --> Aimed at reducing inflammation and pain

- NSAIDs, colchicine, intra-articular steroids, systemic steroids, resting, and ice packs

2. Maintenance --> Aimed at actually lowering uric acid levels in the blood

- Allopurinol (XO inhibitor): Treat patients with tophaceous gout, >2 gout attacks per year, gout with CKD > stage 2 or urolithiasis

- Probenecid (Uricosuric Agents): For urate underexcretors

- Aim to get uric acid levels down to <6 mg or <5 in advanced disease

- Uric acid lowering therapies will actually help break up tophi already present in the joints

Term
Allopurinol Dosing
Definition

- Most commonly used urate lowering therapy --> ~95%

- Start at 100 mg/day but lower to 50 mg/day in CKD >4

- Titrate dose every 2-5 weeks to achieve target range

- Dosing: 100-800 mg daily

- Minor side effects: Skin rash (~2%) --> Mostly in the elderly with renal insufficiency --> Drug renally cleared

- Major side effects: Fever, eosinophilia, severe dermatitis hepatitis, interstitial nephritis with renal failure and vasculitis

- Risk of vasculitis goes up 80-97 times in HLA-B5801 patients --> 25% of vasculitis in these patients

Term
Mobilization Gout
Definition

- Paradoxical flares

- Occurs right after starting urate lowering therapy

- Results after any fast change in sUA levels

- Decreased levels --> Stable urate deposits begin to break up and provides fresh exposure of the crystals to the immune system --> Flare

- Prophylaxis: NSAID or colchicine to prevent this

Term
Calcium Pyrophosphate Dihydrate (CPPD) Crystal Deposition Disease/Pseudogout
Definition

- AKA pseudogout, pseudorheumatoid arthritis, and pseudoosteoarthritis

- Crystals are rhomboid shaped and blue with polarized light is parallel --> Positive biorefringence

- Perpendicular --> Yellow color

Term
Clinical Presentation of Pseudogout
Definition

- Primarily a disease of the elderly

- Acute self-limiting synovitis

- Fever and leukocytosis are possible

- Strong association and overlap with OA presentation

- Common joints: MCPs, wrists, elbows, shoulders, ankles, knees, and hips

Term
Associated Diseases with Pseudogout
Definition

- Aging and osteoarthritis

- Metabolic disorders: Hyperparathyroidism, hemochromatosis, hypothyroidism, hypomagnesemia, and hypophosphatemia

- Hemosiderosis

- Disease can be either sporadic or familial in nature

Term
Treatment for Pseudogout
Definition

- Correct any underlying metabolic disorder or associated disorder if possible

- No specific therapy for removing CPPD deposits

- Treatment of acute attacks and prophylaxis is similar to gout --> NSAIDs, colchicine, ice, rest, steroid injections, etc

Term
Acute Bacterial Arthritis
Definition

- Transmission to joint: Hematogenous spread

- Risk factors: Age, pre-existing joint disease, prosthetic joint, diabetes, immune disorders and IV drug use

- Pathogenesis: Bacteria gain quick access due to the fact that the synovial tissue doesn't have a limiting BM --> Inflammatory cells release cytokines leading to cartilage degradation

- Bacterial pathogens: Staph. aureus, Strep pneumoniae, and Gram negatives

- Diagnosis: Culture, gram stain of synovial fluid, blood, urine, and sputum to identify pathogen

Term
Clinical Manifesations of Acute Bacterial Arthritis
Definition

- Rapid onset of a single swollen and painful joint --> Monoarticular in 80-90% of cases

- Restricted ROM of affected joint

- Fever and leukocytosis --> Not in immunocompromised patients though!!

- Location: knee>hip>shoulder>small joints

Term
Diagnosis of Acute Bacterial Arthritis
Definition

- Synovial Fluid Analysis

- Color: Opaque, yellow/green

- WBC: >20K --> Up to 100K

- Neutrophils/PMNs: >75% of WBCs

- Gram stain --> 70% are positive

- Culture --> 90% are positive

- CPPD and MSU crystal analysis --> Presence does NOT exclude concomitant infection

Term
Complications of Septic Joint
Definition

- Osteomyelitis --> Infection migrates to the bone

- Joint destruction due to inflammation and cytokines

- Ankylosis --> Fusion of joints

Term
Treatment of Septic Joints
Definition

- Intravenous antibiotics for 2-6 weeks depending on pathogen and host --> May need longer course in immunocompromised patients

- Needle aspiration: Initially for analysis but can be done daiy if needed

- Arthoscopic drainage or arthrotomy --> Most common way to clean out joint

- Prosthetic joint: Joint removed and antibiotic impregnanted spacer placed --> Prophylaxis with antibiotics for invasive dental procedures to reduce the likelihood of developing a septic joint

Term
Disseminated Gonococcal Infection (DGI)
Definition

- Should be considered in all sexually active individuals with acute arthritis

- 0.5-3% of patients infected with N. gonorrhoeae

- Risk factors: Women, homosexual and bisexual men, and complement deficiency (C5-C9)

- Can occur in otherwise healthy patients

- Women --> May occur after recent menstrual period or pregnancy/post-partum

Term
Clinical Features of Disseminated Gonococcal Infection
Definition

- Migratory tenosynovitis --> Asymmetric arthritis involving the wrist, knee, ankle and toes

- Pustular rash on erythematous base --> Palms and soles

- Fevers and malaise

Term
Diagnosis of DGI
Definition

- Difficult to culture from synovial fluid --> Only positive in 50% of cases

- Skin lesions are usually sterile

- Blood cultures are also often negative

- Check GU, throat, and rectal culture --> Most likely to be positive

Term
Pathogenesis of DGI
Definition

- Direct joint infection

- Immune-mediated complement fixing arthritis and dermatitis

- Gonococcal cell-wall components, antibody, and complement --> Skin lesions

Term
DGI Treatment
Definition

- IV ceftriaxone --> Within 24-72 hours

- Purulent arthritis --> Drainage and longer course of antibiotics

Term
Viral Arthritis
Definition

1. Parvovirus B19: Fifth disease/erythema infectiosum --> Slapped cheek rash (children), 5% of children and 70% of adults get arthritis

- Diagnosis: Clinical features and IgM serology

- Resolves spontaneously over weeks to months --> Can use NSAIDs

2. HBV: Arthritis before onset of jaundice

- Abrupt, symmetric polyarthritis and tenosynovitis

- 10% of acute HBV infections

- Association with fever and urticaria in 50% 

- Diagnosis: Modest or marked inflammation in synovial fluid

3. HCV: 20% of HCV get arthritis, arthralgias even more common --> 50% of HCV patients develop RF, immun complex formation, and cryoglobulinemia

- Treatment: Antiviral therapy

4. Rubella: Arthritis in 30% --> Maculopapular rash on trunk

- Joint symptoms can preceed the rash and mimic RA

- 15% of patients develop arthritis 2 weeks after vaccination

5. Others: HIV, CMV, HAV, Adenovirus, Coxsackie, EBV, and Mumps

- Pathogenesis: Direct invasion, immune complex or molecular mimicry

Term
Tuberculous Arthritis
Definition

- Chronic monoarthritis of the knees or hips

- Insidious onset without signs of inflammation

- Delayed diagnosis is pretty common

- Musculoskeletal TB in <5% of all TB cases

- AFB+ in 20%

- Diagnosis: AFB, culture, and synovial histology

- Treatment: Multi-drug treatment --> TB treatment for 9-12 months

Term
Fungal Arthritis
Definition

1. Candida: Chronic monoarthritis

2. Coccidiomycosis: Chronic monoarthritis --> Common in the Southwest

3. Sporotrichosis: Chronic monoarthritis

4. Histoplasmosis: Mostly self-limited, immune based and polyarticular

5. Blastomycosis: Acute and septic joint picture --> Common in the Ohio River Valley

Term
Acute Rheumatic Fever (ARF) and Arthritis
Definition

- Systemic immune response to Group A Strep antigens --> Cross reaction and molecular mimicry

- Up to 3% of untreated strep pharyngitis and possible in skin Strep too

- Genetic factors predispose risk

- Patients rarely present over the age of 30

- JONES Criteria: Joints, Carditis, Nodule, Erythema marginatum, and Sydenham's chorea/St. Vitus Dance

Term
Presentation of ARF
Definition

- Minor Criteria: Fever, elevated ESR/CRP, and prolonged PR interval

- JONES Criteria: Joints, cardiac, nodules, erythema marginatum, and Sydenham's chorea

- Evidence of antecedent Strep infection with throat culture, rapid strep test or elevated antistreptolysin-O titer

Term
Clinical Features of ARF
Definition

- Migratory polyarthritis --> Each joint inflamed up to 1 week, then moves --> Knees, ankles, elbows and wrists

- Carditis: Pericarditis, myocarditis or valvulitis --> Aschoff body within myocardium

- Erythema marginatum: Only in 2%, non-pruritic, trunk and proximal extremities, and may be induced by heat applicaiton

- Nodules: Firm, non-tender nodules --> 1% of cases

- Sydenham's Chorea: Random tic and jerk-like movements --> 10% of cases

Term
Treatment of ARF
Definition

- Penicillin for 10 days

- High dose NSAIDs or aspirin

- Prednisone for severe carditis/CHF

- Prophylaxis: Continuous penicillin prophylaxis to prevent futher carditis or valvulitis

Term
Lyme Disease and Arthritis
Definition

- Borrella burgdorferi infection via Ixodes scapularis tick

- Early (<1 month): Erythema migrans and migratory polyarthralgias

- Disseminated (<3 months): Meningitis, cranial neuropathy, radiculopathy, heart block and myopericarditis

- Persistent (>2 months): Encephalitis, peripheral neuropathy, and inflammatory monoarthritis of the knee

Term
Diagnosis of Lyme Disease
Definition

- Clinical presentation plus serologic testing

- ELISA initially

- Western blot --> >5 bands present

- False negatives are rare but false positives are common

- PCR of synovial or CSF fluid

Term
Treatment of Lyme Disease
Definition

- Early and late: Doxycyline for 1 month

- CNS disease: IV ceftriaxone --> Crosses BBB

Term
Synovial Fluid Analysis
Definition

- Normal: Clear/yellow, <200-2,000 WBCs, <25% of PMNs, negative gram stain and no crystals

- Non-Inflammatory: Clear, <2,000 WBCs, <25% PMNs, negative gram stain and no crystals present

- Inflammatory: Variable, cloudy, yellow, >2,000-100K WBCs, >50% of PMNs, negative gram stain, and MSU or CPPD crystals

- Septic: Opaque, yellow/green, >20K up to 100K WBCs, >95% PMNs, often positive gram stain, and occassionally crystals present

- Hemorrhagic: Bloody, <200-2,000 WBCs, and varies 25-50% PMNs

- Bursitis: Septic state even with <1,000 WBCs

Term
Aspirin-Like Drugs
Definition

- Non-opioid and non-narcotic analgesics

- Antipyretic analgesics

- NSAIDs

- Cyclooxygenase inhibitors --> COX1 vs. COX2 inhibitors

- COX Conversion: AAs to thromboxanes and prostaglandins

- COX1 is constitutively expressed --> Thromboxane production

- COX2 is expressed only during times of inflammation --> Prostaglandin production

- Varying specificity for COX1 and COX2 between NSAIDs

- Rofecoxib: >50x COX2 selectivity and Celecoxib: 5-50x COX2 selectivity

Term
Acetaminophen
Definition

- Uses: Mild to moderate pain and fever

- Effects: Less effective analgesic and no inflammatory effect

- Preferable antipyretic-analgesics for patients at increased risk of NSAID toxicity

- Biotransformation: P450 transformation --> Toxic intermediate --> Centrilobular necrosis and hepatotoxicity

- Increased hepatotoxicity when glutathione is reduced

- Alcohol reduces glutathione --> Higher quinone detoxified

- Antidotal therapy: N-acetylcysteine --> Repletes hepatic glutathione

Term
Acetaminophen Renal Toxicity
Definition

- Analgesic nephropathy --> Papillary necrosis and interstitial nephritis

- Caused by phenacetin, acetaminophen and NSAIDs

- Phenacetin is biotransformed into acetaminophen

Term
Traditional NSAIDs
Definition

- Aspirin --> Salicylates

- Non-acetylated salicylates

- Ibuprofen and naproxen

- Diflunisal

- Diclofenac

- Meroxicam

- Nabumetone

- Indomethacin --> COX1 and COX2 selectivity

Term
NSAIDs with COX2 Selectivity
Definition

- Celecoxib: 5-50x more COX2 selectivity

- Rofecoxib: >50x more COX2 selectivity --> Not on the market

- Significantly lower GI toxicity due to COX2 selectivity and lack of anti-prostaglandin effect in the GI tract

- Significantly higher risk of MI and stroke --> Depletion of prostacyclin within the endothelium

Term
NSAID Indications
Definition

- Pain relief

- Suppression of inflammatory response

- Functional improvement in RA, spondyloarthropathies, OA, localized musculoskeletal injuries and gout

Term
Salicyates
Definition

- Aspirin

- 81 mg/day --> Anti-platelet effect

- 650-1000 mg/day --> Analgesic effect

- 3 g/day --> Anti-inflammatory effect

- Toxicity: Hyperuricemia, tinnitus, respiratory alkalosis, respiratory and metabolic acidosis, and coma

- GI toxicity: Due to depletion of prostaglandins in stomach wall --> Risk increases with age, Hx, drug abuse, smoking, and slow release tablets --> Managed by adding a PPI or in some cases a prostaglandin analogue

Term
NSAID Renal Toxicity
Definition

- Sodium retention and edema

- COX2 inhibition --> Prostaglandin inhibition

- Increased renin release

- Risk is greater in patients with renal and cardiovascular disease

Term
NSAIDs for OA Treatment
Definition

- Acetaminophen initially

- Can patient tolerate NSAIDs? --> Aspirin intolerance?

- What are the GI, CV and renal risk for the patient?

- Use with PPI with GI history and avoid COX2 drug with CV history

- Does patient achieve a therapeutic effect with maximal NSAID dose?

- Other approaches --> Steroids, opioids, and duloxetine

Term
History and Physical for Musculoskeletal Problems
Definition

- History: Chief complaint, age, gender, duration of pain, location and description of pain, stiffness, swelling, weakness, constitutional symptoms, and sleep disturbance

- Review of Systems: Raynaud's, Skin, sicca syndrome, eye, chest, GI, and urogenital symptoms

- FHx: Spondyloarthropathy, OA, fibromyalgia, RA, gout, psoriasis, and SLE

- SHx: Day to day activities, ability to work, home life, exercise, education, and support systems

- PE: Skin, nodes, eyes, nose, throat, lung, heart, abdomen, and neurological findings

- Joint Exam: Swelling, warmth, redness, ROM, and periarticular tenderness

Term
Distal Interphalangeal Joints
Definition

- Flexes ~80 degrees

- Extends 10 degrees

- OA --> Bony enlargement and loss of motion --> Heberden nodes

- Psoriatic Arthritis --> Boggy synovitis and associated nail pitting

Term
Proximal Interphalangeal Joints
Definition

- Flexes ~100 degrees

- Extends 0 degrees

- OA --> Bony enlargement with loss of flexing --> Bouchard node

- Rheumatoid arthritis --> Boggy synovial thickening, loss of motion, warm and tender

- Combined DIP/PIP Deformities: Swan neck and Boutonniere Deformity

- Swan Neck Deformity: PIP joint slips down below the tendon

- Boutonniere Deformity: PIP pops up between two heads of the tendon

Term
Metacarpophalangeal Joint
Definition

- Flexes ~90 degrees

- Extends ~45 degrees

- Rheumatoid arthritis --> Boggy synovitis --> Ulnar drift due to interossei being stronger on the ulnar side

- Joints can become permanently subluxed as ulnar deviation continues

Term
Carpometacarpal Joint
Definition

- Abduction ~50 degrees

- Extension ~80 degrees

- Adduction 40 degrees

- Flexion 70 degrees

- OA: Grind test --> Pushing metacarpal into joint reproduces pain --> Squaring of the CMC joints

- DeQuervain's tendonitis: Abductor pollicus longus and/or extensor pollicis brevis tendon inflammation --> Tested via Finklestein Test

Term
Radiocarpal/Wrist Joint
Definition

- Flexion ~80 degrees

- Extension ~70 degrees

- Ulnar deviation ~45 degrees

- Radial deviation ~20 degrees

- Pronation ~90 degrees

- Supination ~60 degrees

- RA: Boggy, swollen (usually ulnar), subluxation and radial deviation late

- Carpal Tunnel: Median nerve entrapment --> Pain, dysesthesia, and numbness --> Tinel and Phalen's Sign

Term
Elbow Joint
Definition

- Flexion ~145 degrees

- Supination ~90 degrees

- Pronate ~60 degrees

- Lateral epicondylitis (tennis elbow) --> Extensor carpi radialis brevis pain --> Pain on resisted wrist extension

- Olecranon bursitis --> Fluid filled due to trauma, septic joint, or crystal --> Septic even with WBC <1,000

- RA: Loss of motion and synovitis

Term
Shoulder Joint
Definition

- Flexion 180

- Abduction 180

- Extension 45

- Internal rotation ~80

- External rotation ~80

1. Rotator Cuff Tendonitis: Supraspinatus, infraspinatus, teres minor, and subscapularis

- Empty can test --> Try to push your had towards the ceiling

- Most commonly in supraspinatus muscle

2. Bursitis with a component of tendonitis

3. Frozen shoulder: Loss of most motions

4. RA

Term
Cervical Spine
Definition

- Chin to chest, chin to shouler, and lateral bending with ear to shoulder

- OA: Commonly 40-50 year olds --> May lead to cervical radiculopathy

- RA: ~50% of RA patients --> Atlantoaxial subluxation (C1-C2) and any level can sublux

Term
Lumbar Spine
Definition

- Flexion ~60, extend ~25, and lateral ~25

- OA: Very common --> ~80% of population

- Ankylosing spondylitis: ~1-3% of the population --> Positive Shober test, chest expansion, finger-to-toe, and occiput to wall tests

Term
Hip Joint
Definition

- Flexion 120, extension 15, abduction 45, and adduction 30 degrees

- OA: Loss of extension and internal rotation --> Flexion is last to go --> Presents as groin pain

- Trochanteric bursitis: Pain on lateral trochanter bursae (3 of them)

Term
Knee Joint
Definition

- Flex 130 and extend 0 degrees

- Examine for fluid, synovial thickening, laxity, and contracture

- Also observe valgus and varus deviation of the legs

- OA: Loss of range of motion, fluid, and pain --> Increased risk with age, overweight, loss of muscle strength, joint abnormality, and trauma

- RA: Boggy and warm joint with fluid build up

Term
Other Causes of Knee Pain
Definition

1. Chondromalacia patella: Patellofemoral syndrome

- Pain, especially when going up and down stairs

- Common sport injury and joint is commonly hypermobile

2. Baker's cyst: Fluid in popliteal fossa

3. Anserina bursitis: Tender below and medial to the knee

4. Internal derangment: Injury to medial meniscus, lateral meniscus and ACL --> Knee locks and gives out

5. Crystals: Gout and pseudogout inflammation

6. Lyme: Huge effusion but relatively asymptomatic

7. Septic Joint: More common in diabetics, elderly, and immunocompromised patients

Term
Ankle Joints
Definition

- Tibiotalar joint: Flexion ~50 and dorsiflexion ~20 degrees

- Subtalar joint: Inversion ~30 and eversion 25 degrees

- RA and reactive arthritis: Lover's heel --> Achilles and plantar fasciitis leading to enthesopathy

- Crystal: Gout and pseudogout

- Tendinitis: Especially in hypermobile patients

Term
Metatarsal Phalangeal Joint
Definition

- OA: Bunion of 1st MTP

- Inflammatory joint disease: RA, psoriatic arthritis, and reactive arthritis

- Crystal: Gout(podagra) and pseudogout

- Dactylitis: PsA and reactive arthritis

Term
Types of Synovial Fluid Causes
Definition

- Non-inflammatory Synovial Fluid: Osteoarthritis, trauma, and Charcot joint

- Inflammatory Synovial Fluid: rheumatoid arthritis, reactive arthritis, gout, pseudogout, lupus, ankylosing spondylitis, psoriatic arthritis, inflammatory bowel arthropathy, juvenile idiopathic arthritis, Lyme, and acute rheumatic fever

- Septic synovial fluid: Staph aureus, Strep, G- species, fungal, and mycobacterial species

Term
Types of Soft Tissue Rheumatism
Definition

- Tendonosis: Trigger finger, lateral epicondylitis, and rotator cuff syndrome

- Bursitis: Subacromial, trochanteric, olecranon, and pes anserine bursitis

- Nerve entrapment: Carpal tunnel, tarsal tunnel, etc

- Hypersensitivity: Fibromyalgia syndrome

Term
Trigger Finger
Definition

- Result of fibrosis and cartilaginous change of the A1 pulley

- Causes stenosis of the flexor tendon

1. Locking with flexion --> Loss of normal gliding with finger motion

2. Tender tendon

3. A1 thickening --> Chondroid metaplasia

- Treatment: Corticosteroid injection and surgical A1 pulley release

Term
DeQuervain's Tenosynovitis
Definition

- Pain over radial styloid with soft tissue swelling

- Pain due to tunnel narrowing at the distal radius

- Presents with a big painful lump right on the radial head

- Treatment: Wrist splint, local steroid injection and surfical release

Term
Carpal Tunnel Syndrome
Definition

- Pain, parasthesia or sensory loss in the distribution of the median nerve --> 1st, 2nd, 3rd, and half of the 4th fingers

- Diagnosis: Tinel's, Phalen's, nocturnal exacerbation, wasting of abductor pollicis brevis

- Treatment: Neutral night time wrist splints, corticosteroid injections, and surgical retinacular release

- >60% of patients had 70% increase with both corticosteroid injections and surgical release

Term
Olecranon Bursitis
Definition

- Due to local trauma, gout, infection, and RA

- Must differentiate between bursitis and elbow joint swelling/arthritis

- Lack of discomfort with full elbow extensions or supination/pronation

- Arthritis: Pain with extension and supination/pronation

- Fluid >1,000 WBCs is compatible with septic bursitis --> Most commonly due to Staph infection

Term
Lateral Epicondylitis
Definition

- Epicondylar pain and tenderness

- Pain on resistive extension of the wrist, fingers, or hand supination

- Treatment: Corticosteroid injection and rest

Term
Shoulder Pain
Definition

- Rotator cuff > Impingement > Acromioclavicular disease > Adhesive capsulitis > Referred pain from the spine

- Referred from cervical spine --> Reproduction of pain on the same side with rotation

- Red flags: Hx of cancer, trauma, loss of rotation, abnormal joint shape, sensory or motor deficit, red skin, fever, and inflammatory symptoms

Term
Common Symptoms of Shoulder Pain
Definition

1. Radicular Neck pain

- Radiating past elbow, worse with neck rotation, "shooting" or "burning" pain, and arm numbness

2. Adhesive Capsulitis: Fibrosis of joint capsule

- History of diabetes

- Shoulder immobilization

3. Rotator Cuff Syndrome: Presents with repeated over head activity --> Empty can test

Term
Physical Exam of Shoulder
Definition

- Supra or infrascapular scalloping and atrophy --> Chronic tendon tear

- Erythema or bulging in the anterior shoulder --> Inflammatory bursitis

- Palpation: AC joint, antero-lateral shoulder, antero-medial shoulder, and anterior shoulder

- Adhesive capsulitis: Loss of motion in all planes

- Glenohumoral joint pathology: Loss of internal rotation

- Osteoarthritis or subacromial calcification: Crepitus

- Remember that the direction for resistive and passive motion is opposite for each muscle group

- Pain on resistance --> Strain>tear

- Weakness --> tear>strain

- External rotation (infraspinatus), internal rotation (subscapularis), abduction (supraspinatus), and hand supination (biceps)

Term
Shoulder Motion Mechanics
Definition

- Deltoids pull the humerus and shoulder joint up

- Supraspinatus, infraspinatus, and subscapularis all keep the humeral head down and in place

- Supraspinatus weakness or tearing --> Superior displacement of the joint due to overcompensated deltoid pulling

- PT for rotator cuff injuries: Strengthens the surrounding muscles (subscapularis) to help keep the humerus down, strengthen rhomboids to decrease impingement, and modify daily routine to avoid repetitive overhead arm use

Term
Subacromial Bursitis
Definition

- Can be confused with GH arthritis --> No passive motion

- Fullness of passive ROM --> bursitis

- Lack of crepitus

- Tear of rotator cuff alongside --> GH effusion will leak into subacromial bursa

- Treatment: Corticosteroid injection

Term
Acromioclavicular Joint Abnormalities
Definition

- Maximal pain with direct palpation of AC joint

- Pain with passive cross body adduction

- DDx: Degenerative joint disease, gout, pseudogout, and infection

- Treatment: Corticosteroid injection or distal clavicle resection

Term
Adhesive Capsulitis
Definition

- Maximal tenderness just lateral to coracoid

- Equal restriction of acute and passive motion --> Lack of motion in all four planes

- Minimal to no crepitus

- Tight posterior capsule --> Diabetes and immobilization may be cause

- Treatment: Passive stretching, corticosteroid injection and surgical capsular release

Term
Radicular Neck Pain
Definition

- Referred shoulder pain

- Flexion and extension --> Normally pt can touch chin to chest and look directly at ceiling

- Pt should be able to move the head to both sides so that the chin is in line with the shoulder

- Lateral bending: 45 degree bend

- Spurling's Maneuver: Extension and ipsilateral rotation followed by downward pressure --> Reproduces pain --> VERY few false positives

Term
Bicipital Tendon Disease
Definition

- Tenderness over the bicipital groove

- Hard to interpret due to its close proximity to greater and lesser tuberosity

- Diagnosis: Maximal pain to resisted forward flexion and hand supination

- Treatment: Corticosteroid injection --> Tendon rupture risk

Term
Trochanteric Bursitis
Definition

- Not a true bursitis

- Tenderness over the greater trochanter: Gluteus medius tendenosis or referred pain from the back

- Trochanteric pain with resistive external rotation: Gluteus medius tendonosis

- Trochanteric pain to resisitive leg abduction: Gluteus medius tendonosis

- Groin pain: Hip arthritis

- Pain to the foot: Lumbar radiculopathy

- Associations: Leg length discrepancy, IT band tightness, gluteal muscle weakness, or back OA

- Treatment: Stretching and conditioning (PT), analgesics, corticosteroid injection, and treat associated disorders

- Corticosteroids help the pain but PT actually deals with the problem

Term
Pes Anserine Bursitis
Definition

- Pain over the pes anserine tendon insertions

- Can be either tendinitis or bursitis

- Treatment: Corticosteroids

Term
Plantar Fasciitis
Definition

- Tightening or fibrosis causing pain of the plantar aponeurosis

- Due to microtrauma but less frequently can be a sign of inflammatory arthritis or enthesitis

- Treatment: heel cup/arch support, stretching/massage, night time splint to stretch out, weight loss, NSAIDs, and occasionally corticosteroid injection

- Negative heel shoes --> Forefoot has more padding than heel --> Stretches out the fascia every time you step down

Term
Osteoarthritis
Definition

- Most common joint disorder: >65 years old, 11% with knee and 5% with hip OA

- Common joints: DIPs, first MCP, cervical spine, lumbar spine, hip, knee, and first MTP

- >30 years old: 6% with knee OA and 2% with hip OA

1. Hyaline cartilage loss and fibrocartilage degeneration/loss --> Cartilage is 70% water, type II collagen, and proteoglycan

2. Bone remodelling and sclerosis

3. Chondro-osteophytes

4. Capsular thickening and distension

5. Synovial inflammation

6. Muscle atrophy and weakness

- Most important metalloproteinases in cartilage degradation --> MMP-13, ADAM-TS4, and ADAM-TS5

Term
Pathogenesis of Osteoarthritis
Definition

- Excessive loading leads to destruction and degradation

- Chemokines and cytokines are involved too

1. Leads to increased MMP activation, cartilage degradation, bone sclerosis, osteophyte production, and overall joint destruction

2. Chondrocytes undergo mitosis and begin to cluster

3. Cartilage cannot be repaired due to its lack of vascular and nervous input

4. Loss of normal cross-linking and weave of normal cartilage --> Reduced compressive rebound of the cartilage

5. Synovial hypertrophy

Term
Major Joint Protectors
Definition

- Muscle and tendon strength and tightness

- Subchondral bone

- Ligaments and joint capsule

- mechanoreceptors

- All of these help to distribute load, absorb load and slow impulses to the joint --> Protect joint cartilage and joint integrity

- Malfunction due to unexpected steps off the curb, neuropathy, repeated impact load and muscle fatigue, and ligamentous disruption

Term
Predisposition to OA
Definition

1. Cartilage unable to respond to repair needs due to excess IL-1 and low IGF-1 levels

2. Cartilage structurally abnormal --> Genetic factors

3. Misshapen or misaligned joint (increased local stress) --> Trauma, developmental, avascular necrosis, and genetic factors

- Stress=load/unit area

- Risk factors: Age, gender, race, genetics, nutritional factors, previous trauma, bridging muscle weakness, bone density, neuropathy, obesity, and injurious physical activities

- More prevalent in women --> Women have weaker muscles 

Term
Occupations and OA Prevalence
Definition

- Cotton workers --> Fingers

- Miners --> Knees and spine

- Jackhammer operators --> Elbows, wrists, and MCPs --> Tools immobilize PNS

- Farmers --> Hips

- Shipyard and Dockyard Workers --> Knees and fingers

Term
Genetics of OA
Definition

- 11-50% of OA may be inherited --> Joint specific

- One gene --> GDF5 --> Especially knee OA

- GDF5 affects the structure of the joint

Term
OA and Running
Definition

- Increased risk of hip OA in elite runners

- Moderate increase in hip OA in casual runners

- No increased likelihood of knee OA with running

Term
Presentation of OA Pain
Definition

- Pain with use

- Relieved with rest

- AM stiffness <30 minutes

- Can present at night if severe

- Joint instability --> Buckling or giving way

- Exam: Tender at joint, effusions possible, bony enlargement (Heberden's nodes), and joint laxity

- Ankylosis also possible over time

Term
Treatment of OA
Definition

- Exercise --> Helps strengthen surrounding muscles, etc

- Biomechanical treatments --> PT

- Drugs --> Acetaminophen, NSAIDs, local steroid injections, COX 2 inhibitors, capsicin, hyaluronic acid injections, and glucosamine

- Weight loss

- Heat/cold application

- Surgery: Knee or hip replacements are very successful for severe OA --> Unresponsive night pain, major immobilty, and unacceptable reduction in ability to walk or work

- Assistive devices: Canes, crutches, and walkers

- Orthotics: Braces, splints, collars, corsets --> Stabilize joint

- Neoprene sleeve to support joint --> Fitted brace to realign joint and reduce OA caused by misaligment or misshapen joints

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