Musculoskeletal Flashcards
Valgus
knock-kneed (2-5 degrees at baseline in normal knees)
Varus
Bow-legged
Patella baja
Abnormally low-lying patella
Patella alta
Abnormally high patella
Infrapatellar bursitis
“Roofer’s knees”
- Seen in someone on knees repeatedly
- Often bilateral (vs suprapatellar)
Knee movement: extension
Quadriceps muscle
L4 (Femoral nerve)
To -5 degrees
Knee movement: flexion
Four flexors, including hamstrings
Sciatic nerve L5-S1
To 130 degrees
Baker’s cyst
Extra-articular swelling mass with transillumination
Popliteal artery aneurysm
Pulsatile mass, nontransilluminable on auscultation
- Bruit
5 Features of ACL tear and assessment
- Acute pain
- Severe swelling
- Audible pop
- Inability to walk
- Clenched fist upon manipulation of knee
- Severe tear may show anterior sag of tibia
Assess for:
- Effusion
- Foot pulses
- Great toe extension= Deep peroneal nerve
- Great toe flexion= Tibial nerve
- Sensation on top of foot= deep peroneal
- Sensation on bottom of foot= tibial nerve
Lachman’s maneuver
To assess for ACL tear
- 80-85% sensitive
Knee stabilized at 25 degrees flexion
Tibia subluxed > 5 mm anteriorly on femur
Anterior drawer maneuver
To assess for ACL tear
- 40% sensitive
Knee stabilized at 90 degrees
Knee subluxed > 5mm anteriorly on femur
Passive crank maneuver
Stabilize humerus, upper extremity in “handshake”
- Palpate head of humerus
- Note pain or limitation of movement
1. Passively internally rotate to 30 degrees
2. “” external
3. “” abduct humerus
Auenbrugger’s maneuver
Auscultatory percurssion
- Stethoscope over AC joint, tap on olecranon
- Diminished sound= discontinuous structures (fractured humerus or scapula)
Abduction of humerus
170 degrees
- Baseline to 100 degrees intrinsic
- 100 to 170 degrees extrinsic
Apley scratch test
Infraspinatus: brush hair
Subscapularis: unhook bra
Yergason’s maneuver
Patient in neutral handshake position
- Examiner inspects anterior shoulder
- Patient supinates forearm, flex elbow against resistance
- Pain at bicipetal groove= bicipetal tendonitis
Elbow passive ROM
Passively flex to 130
asdf
Elbow active ROM
Active flexion= biceps brachiii C5 musculocutaneous
Active extension= trceps C7and radial nerve
Active pronation: pronator teres
Active supination: musculocutaneous
Medial epicondylitis
Pain with active flexion, pronation
Pronator syndrome
Pain, tingling on palm of forearm to digits 1, 2, 3
Postive Tinel’s test
- Entrapment of proximal medial and branch of anterior interosseous nerve
Cubital tunnel syndrome
Pain and tingling of ulnar forearm, hand
- Positive Tinel’s test
Severe:
- Weakness to finger 2-5 abduction/adduciton
- Weakness in flexion of digits 4, 5 when making a fist
- Atrophy of intraosseous muscles
Olecranon bursitis
Serous= cool, non-erythematous, fluctuant mass
- Transilluminable
- “Student’s elbow
Infected olecranon bursitis
- Fluctant warm, red, tender, non-transilluminable mass
Tophi= 1+ firm, nontender, gritty nodules
- Yellow-colored papules
Rheumatoid nodules
- Subcutaneous, firm nodules
- Aponeurosis of triceps muscle`
Radial tunnel syndrome
Pain and tingling of dorsal side of forearm–> digits 1, 2, 3 + anatomic snuffbox
- Positive Tinel’s over radial tunnel
- No motor deficits
Vs Radial head fracture=
- pain in lateral elbow to snuffbox with a “Squeeze sign” (pain on lateral, antecubital elbow)
- decrease in passive/active supination and pronation
Rheumatology
Incorporates Inflammatory states: - Autoimmune (RA, SLE, Vasculitides) - Autoinflammatory (Gout, Juvenile RA, TRAPS, FMF) Non-inflammatory musculoskeletal states: - Degenerative disease (osteoarthritis)
Autoimmune disease
Inflammatory state
= Immune system response against “self” antigens
- Characterized by B and T lymphocyte activation and autoantibody production
- Selection in Thymus destroys “self” reactive T-cells (needs low affinity for thymus cells to survive)
Innate system:
1. Antigen-presenting cells:
- Phagocytes, NK-cells, dendritic cells, epithelial surfaces, non-antibody molecules (activated cells)
- B cells (adaptive) and T cells (adaptive)
Antigen-presenting cells
- Express Toll-like receptors (TLR) in their surface
- Internalizes and presents antigens
- Secrete co-stimulatory molecules (CD80, CD86)
- Secrete cytokines: regulate process
B cells
- B cells also recognize antigens via surface receptors
- Antigens are internalized and processed into peptide fragments
- Fragments bind to MHC molecules (B cells are also APC) and are
- Recognized by T cells
- T cells become activated
T cells
- T cells mature in the thymus
- T cell activation requires recognition of MHC+peptide (signal 1) and
- Co-stimulation (signal 2). Ex CD28 (APC) by CD80/86 (T cells) or CD40 (APC) by CD40L (T cells)
- In the absence of signal 2, T cells undergo apoptotic death
T-cell types and stimulating interleukins: 1. APC presents native T cell with: Th-1: IL-12, IL-18 Th-2: IL-4 Th-17: IL-6, TGF-beta Treg: Il-2, TGH beta 2. Nucelated cell presents native T-cell: Forms Cytotoxic T-cell
T-cell goes to Thymus:
- Positive selection= low affinity for “self”
- Negative selection= high affinity for “self”–> destroyed in Thymus
Autoreactive T cells in periphery
May escape negative selection Inactivated in periphery by: - Immune ignorance (hidden in body in eye, brain, testes--> won't react) - Anergy - Suppression by regulatory T cells
Autoreactive B cells
Produce antibodies that recognize self antigens
Autoantibodies are randomly generated during B cell development
Mechanisms to prevent self-reactive B cells from maturing:
- clonal deletion (delete autoreactive B cell clones)
- anergy
- editing (rearrangement of B-cell receptor–> no longer self-reactive)
- apoptosis
Mechanisms inducing defects in “self” tolerance
- Immunization with self-antigens in presence of adaptive immune system stimulants (adjuvants)
- Etiology: Genetics, sex/sex hormones, environmental triggers
See:
- self-antigen recognition by lymphocytes
- autoantibody production
- tissue damage
Genetic predisposition to autoimmune disease
Studies of familial concordance for SLE and RA:
- 25-40% identical twin concordance for SLE or RA
- Inherited deficiencies of HLA class III genes encoding for C1q, C2 and C4A and C4B (1-2% of patients with SLE )
- Spontaneous polymorphisms of HLA class II genes (HLA DR2 and HLA DR3 among others) in SLE or association of HLA-DR genes with RA
- Mutations in non-HLA genes ( ex FCGR2A, FCGR3A, IRF5 association with SLE, or PTPN22 association with SLE and RA)
Sex/sex hormone effects on autoimmunity
Strong female predominance in SLE (F:M 9:1 ratio) due to:
- Dose effect of X chromosome: 2 X chromosomes confer higher risk than 1 X, independently of sex hormones
- Hormone (estrogen and prolactin) effect on survival and activation of T and B lymphocytes antigen presentation and autoantibody production
Environmental effects on autoimmunity
Examples of environmental triggers:
- UV exposure can cause disease exacerbation
- Medications can cause SLE-like syndrome
- Silica can cause Scleroderma-like disease
- DNA or RNA viruses can activate the immune system, however there is no clear association with specific autoimmune disease
- Smoking, viral and bacterial (P gingivalis) effect in RA
Molecular mimcry
B-cells cross-react against foreign and self-antigens
- Escape tolerance (allowed to survive)
- Stimulated by foreign antigen, become hyperactive against self-antigen
Example: Rheumatic heart disease:
- Antibodies to M protein of Group A strep cross-react with cardiac myosin
Effector mechanisms of autoimmune disease
Antibody-mediated:
- Injury from anti-tissue antibody
- Leads to tissue injury - Injury from immune complex deposition
Cell-mediated tissue damage:
1. Central and peripheral T-cell tolerance defects
- Cytokines released by T cells:
- Th1–> IFN-gamma–> cell-mediated immune responses
- Th2–> IL-4–> B-cell class-switching, Ig produciton
- Th17–> IL-17–> recruit neutrophils, macrophages to infected tissues
- Treg–> IL-10, TGF-beta–> regulate autoreactive cells, inhibit Th1 responses - RNA (virus)–> activates TLR7 on dendritic cells:
- IFN-alpha released:
- Promotes autoreactive T-cell survival; promotes B cell differentiation, plasma cell production; activates more dendritic cells (increased responsiveness to nucleic acids)
Actinomyces in oral cavity
Saprophitic, gram positive anaerobic bacteria
- Part of normal flora
- Colonize tonsillar reypts, dental plaque, ginigval sulci
- Acute form= painful abscesses
- Chronic form= granulomatous inflammation, abscesses that drain by fistula formation
Ameloblastoma
Tumor arises from enamel organ or progenitor cell lines
- Develop soft tissue components of odontogenic epithelial
- Benign, slow-growing, locally inasive
- Arise in mandibular ramus, maxilla, floor of nasal cavity
Histo:
- Islands of proliferating odontogenic epithelium reminiscent of enamel organ
- Basophilic columnar cells at periphery with reverse polarization (nuclei away from basement tissue)
- Edematomous cells in nests or cords
Treatment:
- Wide surgical ressection
- Long-term follow up due to 25-55% recurrence rate
Salivary gland benign neoplasm: Pleomorphic adenoma (benign mixed tumor)
- MOST COMMON salivary glands neoplasm
- Most commonly in the PAROTID followed by minor salivary glands
- Wide age at presentation
- PAINLESS, slowly growing mass, mobile
- Paresthesia due to nerve compression - rare
Histo:
- Well-circumscribed, variably encapsulated mass
- Multinodular (esp. in recurrent disease)
- Composed of three cell types:
1. Epithelial glandular ductal structures
2. Myoepithelial cells
3. Mesenchymal stroma: myxoid, chondroid, hyalinized, osseous
Treatment:
- Surgical excision
- Recurrence rate: 45% after simple enucleation (due to lack of encapsulation or incomplete removal)
- Recurrence rate: 2.5 % with superficial or total parotidectomy
- Malignant transformation – in 2-7%
Warthin’s tumor
- Second most common benign salivary gland tumor
- Characteristically presents in the parotid
- Bilaterality or multifocality occurs more frequently than any other tumor, and it is synchronously identified with other tumors more than any other tumor type
Histo:
- Circumscribed, solid/cystic. Cysts may contain yellow-brown fluid.
- Papillary fronds and cystic spaces lined by double layered oncocytic epithelium
- Dense lymphoid node-like stroma intimately associated with the epithelial component
Treatment:
- Surgical excision
- 4-25% recurrence due to multifocality or incomplete excision
Mucocele (salivary gland)
The most common non-neoplastic lesion of salivary glands
- “Pooling of mucin in a cystic cavity”
Types:
- Retention type – mucin pooling confined within a dilated excretory duct
- Extravasation type – escape of mucin from the duct system into connective tissue – most common type
Seen in: lower lip, tongue, floor of mouth, palate
Presentation: soft, fluctuant semitranslucent painless swelling that may occur after a traumatic event
Treatment - complete excision, including minor salivary gland
Sialolithiasis (salivary gland)
Collection of concretions which form a stone within the salivary gland excretory duct system (stone in duct)
- Most common involves the submandibular gland (Wharton’s duct) and may cause a chronic sialadenitis distal to the stone.
- Always visible on radiographic examination
- Nidus of cellular debris in the center of concentric laminated calcium deposits
Sjogren Syndrome of salivary gland
Describes a characteristic lymphocytic infiltrate in salivary glands; doesn’t commit to an etiologic cause but describes histologic findings
Most cases – women in the 4th and 5th decades
- Associated with or is a precursor of Sjogren’s syndrome
Two types:
- Systemic: collagen vascular disease
- Localized to salivary and lacrimal glands
Pathology:
- Uni or bilateral enlargment of parotid glands with preserved lobulation
Histo:
- Periductal chronic inflammation extending into acini
- Glands replaced by polyclonal lymphocytes, germinal centers, plasma cells
- Lesion= lymphoepithelial sialadenitis (epimyoepithelial islands)
- Similar changes present in minor salivary glands in Sjogren syndrome (biopsy smaller glands first)- need clinical diagnosis and serologic specimen to confirm dx
Sinusitis
- Acute:
- Haemophilus, Branchamella - Allergic:
- Hypersensitivity reaction to fungal antigens (atopic patients), aspergillus - Fungus ball (mycetoma, aspergilloma)
- Sinuses with poor drainage; fungi proliferate and form dense mass of hyphae
- DO NOT invade mucosa/vessels - Invasive fungal sinusitis
- Seen in immunosuppressed patients
- Fungi invade sinus mucosa, vessels
- Can spread to venous sinuses, meninges, brain
- High mortality
- Mucormycosis: common in diabetic patients; can involve skin, bone, orbit, brain
Schneiderian Papilloma
Benign sinus papilloma
- Schneiderian membrane: the ciliated columnar epithelium of ectodermal origin that lines the nasal cavity (except the nasal vestibule and the superior wall of the nasal cavity)
- Papillomas derived from the schneiderian membrane:
1. Inverted (endophytic)- most common
2. Exophytic
3. Columnar cell (oncocytic)
Inverted Papilloma
Location: lateral nasal wall, middle meatus, paranasal sinuses, rarely in the nasopharynx or middle ear
Clinical presentation: nasal obstruction, epistaxis, rhinorrhea, facial pressure
CT, MRI – unilateral polypoid mass filling the nasal cavity, +/- displacement of nasal septum and opacification of sinuses
Histo:
- Markedly thick , inverted neoplastic proliferation replacing mucoserous glands and ducts
- Transitional/squamoid epithelium with numerous intraepithelial microcysts containing cellular debris
- Stroma: edematous, myxomatous, fibrous. No seromucinous glands in the stroma
Prognosis:
- Recurrence: up to 60% of cases (depending on type of surgery)
- Malignant transformation (squamous cell carcinoma): in 10% of cases
Nasopharyngeal angiofibroma
- Benign, highly cellular and richly vascularized mesenchymal neoplasms that arise in the roof of the nasopharynx
- Exclusively in YOUNG MALES (mean age 15yo)
- There is an association with FAP
Presentation:
- Nasal obstruction, spontaneous epistaxis, nasal drainage
- Endoscopy – mass involving the posterior nasal wall
Treatment:
- Preop angiography – identifies the feeding vessel and allows for presurgical embolization (reduces risk of surgical hemorrhage
Histo:
- Round, nodular nonencapsulated masses with a sessile or pedunculated base
- Tumor surface – covered by intact mucosa (+/- focal ulceration)
- Microscopic: 3 elements:
1. abnormal vascular network (lack muscular wall- can’t constrict, can cause hemorrhage),
2. connective tissue stroma (fine and coarse collagen)
3. stromal cells (cytologically bland spindle cells)
Treatment:
- Selective angiographic embolization, surgical excision
- Local aggressive growth, recurrences in 20% of patients, usually within the first 2 years after diagnosis
- Mortality – up to 9%, due to hemorrhage
Cholesteatoma (ear)
Destructive squamous epithelial cyst of middle ear or mastoid region
- usually secondary to chronic otitis media, but occasionally congenital
- Origin in superior posterior middle ear, may demonstrate locally aggressive growth into adjacent structures
Presentation:
- May lead to progressive conductive hearing loss
- Intracranial extension may lead to lethal complications: meningitis, epidural abscess, lateral sinus thrombosis
- Otorrhea, otalgia, tinnitus, vertigo;
- Otoscopic appearance: white-gray to yellow irregular mass associated with otitis media or perforated tympanic membrane
Treatment: surgical extirpation of the squamous epithelial lining is essential
Malignant External “Otitis” (MEO)
Infection of the external auditory canal which progresses to a highly aggressive, invasive osteomyelitis of the temporal bone and skull base, most often in immunocompromissed patients
> 90% of cases: in DIABETICS, most over 60 yo
- Initiated by minor trauma (cleaning ear) to the external auditory canal mucosa that allows entry of an opportunistic agent (Pseudomonas aeruginosa)
- Can lead to invasive osteomyelitis of skull base
Clinical presentation:
- Erythema of the auricle and ear canal, otalgia
- Severe headache, purulent otorrhea
- Clinical exam: granulation tissue on the floor of the external auditory canal
Histo:
- necrotic material and granulation tissue
- Culture of debridement specimen is crucial in the management of MEO
Treatment:
strict diabetes control, careful debridement and IV multidrug antibiotic treatment
Tumors of the ear:
Jugulotympanic paraganglioma and Schwannoma
Jugulotympanic paraganglioma:
- The most common benign tumor of the middle ear
- Slow growth (years)
- Cells with lobular arrangement; rich, vascular stroma
Schwannoma:
- The most common tumor of the inner ear
- Nearly all arise from vestibular nerves
- Bilateral Schwannomas are common in NF2
Branchial cleft anomalies
Lateral cervical cyst that results from congenital/developmental defects arising from the primitive 2nd branchial apparatus
- 80-90% of branchial anomalies are associated with the second apparatus
- Lateral neck, near the mandibular angle
- Equal gender distribution, 75% of patients between 20-40 yo
Clinical presentation
- Mass along the anterior border of the sternocleidomastoid muscle
- Painless, long duration
- May become secondarily infected
Prognosis, treatment:
- Complete excision
- Recurrence rate 2.7%
Histo:
- Unilocular cysts, 2-6 cm
- Lining: stratified squamous epithelium (90%), respiratory epithelium, or both
- Keratinaceous debris inside the cyst
- Lymphoid aggregates with or without germinal centers beneath the epithelial lining
- Acute and chronic inflammation, foreign body giant cell reaction and fibrosis
Erythrocyte sedimentation Rate
Detects rate erythrocytes fall in column
- Should fall at ~ 10 mm/hour
- Faster rate of fall= erythrocytes stick together (aggregation)
- Inflammatory proteins increased erythrocyte stickiness
Elevation of ESR caused by:
- Acute-phase reactants (fibrinogen)
- Monoclonal Ig
- Anemia
- Polycythemia
- Malignancy
- Inflammation secondary to infection
Affected by:
- Age
- Gender
- Race
** ESR and CRP can predict radiographic progression of disease (but markers may not be present)
C-reactive protein (CRP)
Produced in response to inflammatory cytokines (IL-1, IL-6, TNFa)
Increases rapidly for 2-3 days
Half-life is ~19 hours (unless there is continuous infection, inflammation, malignancy)
- Abnormal elevation can rapidly correct in non-chronic conditions
Activates the classic complement pathway
Binds to Fc gamma receptor
Normal/minor elevation ( < 1mg/dL):
- Vigorous exercise
- Common cold
- Pregnancy
- Gingivitis
- Seizures
- Depression
- Insulin resistance and diabetes
- Obesity
Moderate Elevation (1-10mg/dL)
- Autoimmune diseases (Most connective tissue diseases, Rheumatoid arthritis)
- Myocardial infarction
- Malignancies
- Pancreatitis
- Mucosal infection (bronchitis, cystitis)
Marked Elevation (>10mg/dL)
- Acute bacterial infection (80%-85%)
- Major trauma
- Systemic vasculitis
Affected by:
- Gender
- Race
** ESR and CRP can predict radiographic progression of disease (but markers may not be present)
Complement levels and assessment of inflammatory disease
Ex: C3, C4, CH50 levels decrease when disease is active (using up complement!)
- CH50= marker of complement activity (not as useful as C3, C4)
- Initial diagnosis of Systemic Lupus Erythematosus
- Assessing SLE activity
- Assessing response to treatment
- Diagnosing or assessing activity of cryogobulinemia
- Rheumatoid vasculitis
- Sjogren’s syndrome: normal C3, low C4
Rheumatoid Factor
IgM or IgG antibody against Fc portion of IgG
RF in Rheumatic/autoimmune disease:
- Rheumatoid Arthritis
- SLE
- Sjogren’s Syndrome
- Mixed Connective Tissue Disease
- Mixed Cryoglobulinemia
- Juvenile Chronic Arthritis
- Psoriatic Arthritis
RF in non-Rheumatic diseases:
- Lymphoproliferative Syndromes
- Other Malignancies
- Viral or parasitic Infection
- Hepatitis C
- Usually IgM of lower affinity, polyspecific (reacts to two unrelated antigens such as ssDNA, thyroglobulin, histone and other antigens)
CCP antibodies
Recognize enzymatic post-translational modification of Arg to Citrulline
- Citrullination (deimination) catalyzed by Peptidyl Arinine Deiminase (PAD1)
- Binds to citrullinated peptides (NOT similar peptides containing Arg)
Similar sensitivity (53-68%) but higher specificity (95-96%) than RF for diagnosis of Rheumatoid Arthritis
Associated with erosive and deforming potential.
Detectable early in the disease course (vs other autoantibodies which may not be detectable until well after symptoms start)
Protein products targeted by CCP autoantibodies:
- Collagen Type II
- Fibrinogen/fibrin
- Wimentin
- IgG (Fc)
ANA= Anti-nuclear antibodies
Antibodies that bind nuclear factors, including double stranded DNA, histone proteins, RNA/Protein nuclear complexes
Method:
- HEp-2 Cells in dish
- Add patient’s serum in serial dilutions
- Add fluorescent anti-human Antibodies
- Will fluoresce if patient’s Ab are targeting nuclear antibodies (fluoresces over nucleus)
ANA type= highest dilution (high titer) of serum where immunofluorescence visible
- Indicates high concentration of autoantibody if reaction occurs even with lots of dilutions
- Titer does not necessarily correlate with disease activity or prognosis
SLE: ANA is 95% sensitive, but lacks specificity. Could also be:
- Scleroderma
- Mixed connective tissue disease
- Polymyositis/dermatomyositis
- Rheumatoid arthritis
- Sjögren’s syndrome
- Hepatitis C (15%)
- HIV (15%)
- Subacute bacterial endocarditis
- Tuberculosis
- Malaria
- Multiple sclerosis (23-30%)
- Liver disease: Primary biliary cirrosis
- Graft Versus Host Disease
- General population ( 3-5%) with no autoimmune disease (autoreactive B cells present without disease)
** May be able to detect ANA years before SLE diagnosis (50% had positive test 5 years before diagnosis)
Subtypes of ANA
- Anti-Smith (SLE- 95% specific, 30% sensitive), Anti-RNP (SLE, mixed connective tissue disease): Antibodies to extractable nuclear antigens (ENA)
- Antibodies to nuclear, non-coding RNA-containing protein complexes
- Specific but not sensitive - Anti-SSA (40% SLE, Sjogren’s), Anti-SSB (40% SLE, 15% Primary Sjogren’s)
- Antibodies to nuclear, non-coding RNA-containing protein complexes
- Specific but not sensitive
* * Anti-SSA/Anti-Ro antibodies can cross placenta, can cause neonatal lupus (RARE). Can vary from facial rash, transient liver enzyme abnormalities to fetal cardiac disease (heart block) - Anti-dsDNA:
- Antibodies to nuclear, dsDNA
- 60-70% specific to SLE - Anti-centromere antibodies: limited to scleroderma (CREST)
- Anti-Scl-70 antibodies (topoisomerase I): 90% specific, not sensitive for scleroderma
- Anti-histone antibodies: 95% specific for drug-induced lupus
Antiphospholipid antibodies
Target cellular membranes
Confer increased risk for Antiphospholipid antibody syndromes (APS):
- Thrombosis
- Pregnancy morbidity
- Thrombocytopenia
** Can detect similar antibodies after infections like Lyme, Malaria
Types:
- Anti-cariolipin antibodies (IgG, IgM, IgA)
- Detected by ELISA - Beta 2 glycoprotein I (B2GPI) antibodies:
- Directed against phospholipid-binding plasma protein
- Detected by immunoassays - Lupus anticoagulant
- Tests for Inhibitor of phospholipid-dependent clotting
Anti-nuclear cytoplasmic antibodies (ANCA)
c-ANCA= target proteinase 3 (PR-3)
Associated with:
- Granulomatous polyangitis (GPA) also known as Wegener’s disease
- Churg Strauss (eosinophilicGPA?)
- Microscopic polyangiitis (MPA)
- Renal-limited vasculitis (ANCA-associated kidney disease)
p-ANCA= target myeloperoxidase (MPO) and elastase, cathepsin, lysosyme, lactoferrin
Associated with:
- Churg Strauss (eosinophilicGPA?)
- Microscopic polyangiitis (MPA)
- Renal-limited vasculitis (ANCA-associated kidney disease)
- Inflammatory bowel disease
c-ANCA OR p-ANCA seen in:
- Drug-induced
- CTDs (SLE, RA, Sjogren’s)
- Bacterial Endocarditis caused by S. Aureus or S. viridans (cANCA more common than pANCA)
- Paraneoplastic syndromes (lung, esophageal cancer, leukemia, lymphoma)
Inflammatory Myopathy Antibodies
Detected in 30-40% of inflammatory myopathies
Anti-synthetase (Jo-1): associated with interstitial lung disease (ILD), Raynaud’s, mechanics’ hands, in polymyositis or dermatomyositis and with moderate response to treatment.
Anti-Mi2: associated with dermatomyositis and may be indicators of good therapeutic response and prognosis
Anti-SRP: may be associated with cardiac disease and severe weakness.
Epidemiology of RA
Relatively common disorder
- Affects >1% of the population of North America
- Female:male 2.5:1
- Incidence increases with age (Peak: 4th-6th decade)
Pathogenesis of RA
Familial aggregation
Environmental or infectious factors
Chronic, systemic autoimmune disease
Primarily mediated by T lymphocytes
Primary target tissue: synovium
Synovial tissue is infiltrated by T lymphocytes
- Identified T-lymphocytes as culprit based on RA HIV patients who went into remission when CD4 lymphocyte count low
Imbalance in cytokines between:
- anti-inflammatory (IL-10, TGF-beta, IL-4, sTNFR, sIL-1R, IL-1Ra) and
- Inflammatory (TNF, IL-1, IL-6, LIF, LT-alpha, chemokines)
Genetic predisposition: MHC class II, non-MHC genes (HLA-DRB 0401,0404 in whites)
Shared epitope on the hypervariable region–> AG binding & presentation –> CD4+T cell activation –> non-T effector cells –> cytokine production
–> T-cell recruitment
–> chronic inflammation
—> Bone, cartilage, ligament, tendon damage
–> erosions, joint deformity
Synovial inflammation:
- Fluid filled with neutrophils
- Pannus infiltrated by T lymph, macrophages, fibroblasts, plasma cells, endothelial dendritic cells
Clinical presentation of RA
Bilateral, symmetrical Large and small joints Inflammation of the synovium Fluid accumulation in the joint Joint swelling and pain If not diagnosed and treated vigorously--> destruction, deformity, disability
Associated with shortened life expectancy
Constitutional symptoms: low grade fever, wt loss, anorexia, fatigue
Extra-articular involvement:
- Lungs, skin, heart, hematologic, eye, vessels
- Rarely: CNS (rheumatoid nodules), kidneys
- Differentiate from drug side effect!
Diagnosis of RA
Joint involvement at time of onset:
- Polyarticular (75%)
- Small joints of hands and feet (DIP joints)
- Large joints - Monarticular (25%)
- Knee, shoulder, wrist, hip, ankle, elbow
Need to examine joints:
- Should be soft, elicit tenderness
1. Psoriatic arthritis= inflammation of joint
2. Osteoarthritis= swelling of bone at joint
Bone scan: demonstrates inflammation of bone
X-ray: Protrusio acetabulum (hip protrudes into pelvis
Late RA:
- Atrophy, ulnar deviation of joints in hands
- Rheumatoid nodules (not inflammatory, mainly fibrotic)- seen outside joint space
- Loss of cartilage
- Pannus eats away at bone on edges of joints
Autoantibodies in RA
Two most important:
- Fc region of IgG= Rheumatoid factor (IgM- most common, or IgG)
- Citrullinated proteins (don’t bind arginine-containing peptides, do bind same proteins once converted to citrulline)
Diseases associated with Rheumatoid factor
RA (80%) Juvenile inflammatory arthritis (20%) Sjogren’s Syndrome (90%) Lupus (40%) Scleroderma Sarcoidosis Cryoglobulinemia Cirrhosis Post-vaccination Aging
Chronic Infections:
- Subacute bacterial endocarditis
- Hepatitis C
- TB
Overlap Syndromes:
- Ankylosing Spondylitis (< 15%)
- Cryoglobulinemia (> 90%)
- Psoriatic arthritis (negative)
- Reactive arthritis (negative)
APCA (anti-CCP)
- detectable already years before the first clinical symptoms
- also predictive for the level of erosiveness
APCA detection in clinical practice:
- Effect of Smoking
- Earlier, worse arthritis in ACPA+ smokers - Differentiate RA from arthritis in HCV infection
- positive RF 12/14pt, negative aCCP–> probably arthritis, not RA - Predict erosive and progressive disease
- Combination of anti-CCP and IgM RF
Testing for RA
- Object is to confirm the presence of a systemic inflammatory process
- Evaluate for serious major organ involvement
- Check for pertinent but unusual causes of systemic polyarthritis
Labs:
- CBC: anemia, nL or slightly elevated WBC, and/or platelet
- ESR elevation
- CRP elevation
- BUN, creatinine
- Liver enzymes
- ANA (not usually positive)
- Hepatitis C
Imaging:
- X-rays (only helpful with later damage)
- U/S: synovial swelling, hypertrophy; doppler to show increased blood flow in inflammatory state
- MRI
- Bone scan
- Arthrocentesis, synovial fluid analysis
Classification criteria for RA
DO NOT NEED TO MEMORIZE: Score of 6+ needed for classification of RA: A. Joint involvement: 1 large joint= 0 2-10 large joints= 1 1-3 small joints= 2 4-10 small joints= 3 > 10 joints (at least one small)= 5
B. Serology
Negative RF, negative CCP= 0
Low-positive RF, low-positive CCP= 2
High-positive RF, high positive CCP= 3
C. Acute-phase reactants:
Normal CRP and normal ESR= 0
Abnormal CRP, abnormal ESR= 1
D. Duration of symptoms
< 6 weeks= 0
6+ weeks= 1
Articular manifestations of RA
Hands:
- Ulnar deviation
- Swan-neck deformity
- Boutonnière deformity
- Tenosynovitis
- Extensor tendon rupture
- Carpal tunnel
Knee
- Synovitis causing Baker’s cyst (rupture-DVT)
Feet
- MTP joints cock-up deformity
- talonavicular joint-pronation
- eversion of the foot
- ankle joint-tarsal tunnel syndrome (burning paresthesia of the sole)
Spine
- Tenosynovitis of the C1 transverse ligament–> C1-C2 instability
- Erosion of odontoid process
- myelopathy
Extra-articular manifestations of RA
Subcutaneous Nodules Vasculitis - Arterioles, capillaries, venules - Mostly leukocytoclastic vasculitis - Skin ulcerations (necrotizing)
Nervous system:
- Myelopathy
- Mononeuritis multiplex:
- disorder characterized by simultaneous or sequential damage to more than one nerve group
- isolated damage to at least 2 separate nerve areas
- involves destruction of the axon
- interferes with nerve conduction at the location of the damage (see wrist, foot drop)
- causes include a lack of oxygen caused by decreased blood flow or inflammation of blood vessels. No cause is identified for about one-third of cases - Entrapment syndromes:
- Carpal Tunnel, Tarsal Tunnel etc.
Ocular
- Keratoconjunctivitis sicca (also seen in Sjogren’s)
- Episcleritis (more superficial than scleritis)
- Scleritis
- Scleromalacia perforans (rheumatoid nodule)
Cardiac
- Pericardial effusion
- Paricarditis
- Valve nodules
Pulmonary
- Pleural disease
- Interstitial lung disease
- Pulmonary nodules
Renal
- Amyloidosis (more common with early age of onset–> longer time to develop)
- Drug toxicity
- Papillary necrosis
RA treatment
Goal is complete remission
- Start with anti-inflammatory medications
- NSAIDs
- Corticosteroids - Add immunomodulators (DMARDs) early
- If no significant improvement in first few months add “biologics”
- Antibodies against inflammatory cytokines
Acute monoarthritis: Diagnostic possibilities
Rheumatologic emergency:
- Urgent- investigate thoroughly
Diagnostic possibilities:
- Infections
- Bacterial (most destructive)
- Viral
- Fungal - Crystals
- Monosodium urate (MSU) (Gout)
- Calcium pyrophosphate (CPPD)
- Apatite - Hemorrhagic
- Tumors
- Villonodular synovitis
- Malignancy - Vascular
- Sickle cell disease
- Osteonecrosis - Other
- Hemarthrosis
- Systemic inflammatory arthritis
Diagnostic techniques:
- Aspirate Joint
- Synovial fluid examination:
- Cell count
- Gram Stain
- Culture and sensitivity
- Light microscopy
- Polarized microscopy
Synovial fluid cell count
Normal: Clear, colorless, viscous
- < 200 leukocytes, < 25% PMNs
Non-inflammatory: clear, yellow, viscous
- 200-2000 leukocytes, < 25% PMNs
Inflammatory: cloudy, yellow, watery, low glucose
- 2000-100,000 leukocytes, > 50% PMNs
Septic: Purulent, very low glucose
- > 80,000 leukocytes, > 75% PMNs
Bacterial arthritis: causes
Non-gonococcal bacterial infection: Most serious
- S. aureus: most common
- Streptococcus species
- Gr- and fungi: increasing in frequency; seen in Immunocompromised or debilitated host
Pathomechanism:
- Hematogenous spread (most common)
- Contiguous spread
- Soft tissue-skin infection
- Penetrating trauma
- Surgery
- Adjacent osteomyelitis
- Intraarticular injection (1:500-1:5,000)
Predisposing factors:
- Systemic connective tissue disorders
- OA of the joint
- Diabetes mellitus
- Immunocompromised patients
- Advanced age
- Alcoholism
- Prosthesis or foreign body in the joint
Bacterial arthritis: presentation
Acute severe pain Swelling Increase in joint temperature Fever (+/-) Systemic toxicity (chills etc +/-)
Site:
- Knee > large diarthrodial joints
- In children: knee and hip
- IV drug users: axial (sternoclavicular, SIJ)
- Methicillin resistant S. aureus
- Serratia
- Ps. aeruginosa
Bacterial arthritis: diagnosis and treatment
- Joint aspiration (needle or open)
- WBC: >10,000/mm2 (>50,000/mm2 in 70%)
- Neutrophils: >80%
- Gram stain (+ in 50%, + in 75% for gram+ cocci)
- Culture (+ in >90%) - Blood culture: 50% + in non-GC arthritis
- Increased WBC with left shift
- X-ray findings
- Get a baseline and also to Dx osteomyelitis
- No initial changes, except for effusion
- Osteomyelitis findings (10-20 days to develop)
- Radionucleide imaging, gallium scanning
- CT scan
Tx: start empiric antibiotic!
Gonococcal arthritis
Cause: disseminated GC infection in immunocompetent 60,000/mm2
- Outcome: favorable
Crystalline arthritis
Very common type of arthritis
- Starts monoarticular (Gout, pseudo-gout)
Associated findings:
- Gout:
- HTN,
- hyperuricemia,
- EtOH,
- male (post-menopausal females) - CPPD (pseudo-gout)= Calcium pyrophosphate dihydrate disease
- Older age,
- DJD (degenerative joint disease),
- chondrocaclinosis (calcium in cartilage) on x-ray
Gout: pathophys
Acute arthritis; inflammatory response to MSU (urate) crystals in joints
- Generally starts in 1st MTP joint (big toe)
- Peripheral joints, tendons, any tissue
- Recurent
- Chronic, deforming
- Males/post-menopausal women
- Associated with Lesch-Nyhan syndrome: mutations in the HPRT gene located on X chromosome–> HGPRT enzyme defect–> uric acid buildup
Pathophys:
- Sodium urate triggers immediate immune response (potent trigger)
- Leads to production of IL-1–> inflammatory cascade
- Cells move to site of urate deposition
- Cannot remove urate
- Eventually immune response tapers
Gout: clinical features
Acute attack
- Abrupt, monoarticular
- Involves MTP –> ankle, tarsal joint, knee, wrist, elbow
- Exquisite tenderness, swelling, warmth
- Fever, leukocytosis may occur
- Overlying skin desquamates
- Lasts 3-10 days w/o treatment
Precipitating event of acute attack:
- Trauma, surgery, stress, infection, food (red meat, shellfish), alcohol (beer)
- Diuretics, low dose aspirin
Interval gout:
- Asymptomatic periods shorten
- Attacks increase in frequency
- 10-20 years until chronic phase
Chronic gout (tophaceous gout): Result of: - Years of persistent hyperuricemia - Frequent attacks - Inadequate therapy
Features of chronic gout:
- Joint destruction
- Tophi: subcutaneous tissue, tendons, IP-MCP joints, pinna of ear
- Extra-articular: myocardium, pericardium, aortic valves, extra-dural spinal, kidneys
- May mimic RA but less symmetrical
Gout: diagnosis
Diagnosis
- Crystal in the aspirate:
- Monosodium urate monohydrate= needle shaped
- Differentiate from calcium pyrophosphate dihydrate (pseudo-gout)- NOT needle shaped
- Crystal aligned with polarizer= yellow
- Perpendicular to polarizer= blue
- Negative birefringence (vs CPP= positive birefringence)
- Crystal inside neutrophils= acute gout attack
SF WBC 2,000-100,000/mm3
Other clinical features:
- Serum uric acid may be normal during acute attack
- Urine excretion over 1,000 mg/d is suggestive
X-ray:
- Acute phase
- Soft tissue swelling - Chronic
- Oval, round periarticular or intraarticular erosion (bite-out)
- Sclerotic margin
- Joint space is preserved until late
Chondrocalcinosis
Pseudo-Gout= Degenerative Joint Disease (DJD)
- calcium pyrophosphate crystals in articular, peri-articular tissue
- Idiopathic or associated with certain metabolic diseases
Five types of clinical features:
- chondrocalcinosis: Calcium deposition in cartilage (may be asymptomatic)
- Pseudo-gout (symptomatic)
- Pseudo-osteoarthritis
- Pseudo-rheumatoid arthritis
- Pseudo-Charcot (neuropathic bone destruction
Laboratory Findings
- rod shaped, often intracellular crystals
- positively birefringent (blue, when parallel to the axis of a polarizing microscope compensator)
Evaluation:
serum Ca, Mg, phosphorus, PTH, alkaline phosphatase, ferritin, iron, iron binding capacity, glucose, (TSH), uric acid
Radiologic findings:
- punctate and linear densities in articular cartilage
- Site: knee, acetabular labrum, symphysis pubis, articular disk of the wrist, and annulus fibrosus of the intervertebral discs
X-ray screening:
- AP views of both knees, pelvis, hips, symphysis pubis,
PA view of both hands.
Pseudo-gout
- Acute inflammatory process
- 1 or more joints
- Lasts for several days
- Similar to gout, not as severe
- Smaller, less painful attacks between flares
- Any joints, but knee most often
- Crystal deposition in tendon, ligaments, synovium, cartilage
- More common in elderly, women
Systemic Sclerosis
Systemic autoimmune disease of unknown etiology.
- Autoimmune activation, activation of fibroblasts and deposition of collagen
The third most common systemic autoimmune disease.
More common in females (4-8:1 female to male) and affects all racial groups and all ages.
Peak of disease onset in the fourth and fifth decades.
Familial SSc is rare. There is no evidence of genetic inheritance.
Organ system involvement: Skin 100% Raynaud's phenomena 89 GI tract 87 Lungs 64 Bones/joints 45 Muscles 35 Heart 24 Kidneys 15
Systemic sclerosis: cutaneous involvement
Skin sclerosis in 95% of patients. In 5% there is typical visceral involvement in the absence of skin sclerosis (Scleroderma sine Scleroderma).
Thickened and hidebound skin first appears distally (Sclerodactyly) and progresses proximally.
- Flexion contractures at joints
- Shiny, taut skin
1. Limited cutaneous involvement: - hands, feet, face, forearms and legs.
2. Diffuse cutaneous involvement: - upper arms, thighs, chest, abdomen and back in addition to above.
The face is expressionless with loss of wrinkles, beaked nose, thin lips with radial furrowing, and microstomia.
Diffuse hyperpigmentation or hyperpigmented hair follicles surrounded by depigmented areas (“salt-and-pepper” pattern).
Telangiectasia on the hands, face, lips and tongue.
- Mucosal telangiectasia (gastric, small intestinal or colonic, implicated as a source of gastrointestinal bleeding).
Painful ulcerations at the fingertips and other areas where the skin is tightly stretched.
Cutaneous calcifications at the fingertips, along the extensor surface of the forearms, and periarticular areas.
Raynaud’s phenomenon
Raynaud’s phenomenon is the initial symptom of systemic sclerosis in a majority of patients.
- Often precedes the onset of other SSc features.
- Ultimately develops in virtually all SSc patients.
Is common among premenopausal women, only a minority of whom develop a connective tissue disease, most commonly SSc.
Characterized by abrupt, temporary occlusion of peripheral arteries.
- Triggered by cold exposure, tobacco smoke or emotional stress.
- Typical findings are the waxy blanching of fingers followed by numbness, tingling and paresthesias.
- Restoration of blood flow causes cyanotic discoloration followed by erythema of affected regions.
Irregular capillary beds in Systemic sclerosis exacerbate phenomenon
Systemic Sclerosis: skeletal involvement
X-rays show resorption and often complete dissolution of the distal end of the phalanx (acro-osteolysis).
Indolent myopathy with minimal elevation in serum muscle enzymes (focal muscle fibrosis and fiber atrophy).
Some patients develop typical inflammatory myopathy (polymyositis) with elevation in muscle enzymes and EMG changes.
Systemic sclerosis: GI tract involvement
- Esophageal abnormalities in up to 90% of patients:
- Incompetence of the lower esophageal sphincter and decreased or absent peristalsis in the lower two-thirds (smooth muscle involvement- NOT striated) cause dysphagia and odynophagia.
- Chronic reflux and esophageal stasis cause esophagitis, Barrett`s esophagus and lower esophageal stricture.
- Increased frequency of esophageal cancer in SSc.
- Reflux of gastric contents causes hoarseness, cough and aspiration pneumonitis. - Gastric/esophageal dilation
- Watermelon stomach= Gastric Antral Vascular Ectasia (GAVE) with painless severe GI bleeding
- Disordered motility:
- Gastric distension
- Bacterial overgrowth, diarrhea, malabsorption, pseudo-obstruction
- Colonic disease with wide-mouth sacculation (pseudodiverticula)
Systemic Sclerosis: Respiratory system involvement
Lung involvement is the leading cause of morbidity and mortality in SSc.
Lung involvement results in pulmonary fibrosis (ILD) or pulmonary hypertension.
Pulmonary fibrosis in SSc is insidious at onset and progressive.
Physical exam discloses fine inspiratory crackles at the lung bases.
Pulmonary hypertension and cor pulmonale may develop in patients with limited SSc, even in the absence of pulmonary parenchymal involvement.
Diagnosis:
- Chest roentgenograms are insensitive for detection of early lesions.
- Pulmonary function studies are more sensitive (decreased DLCO, decreased TLC).
- Isolated reduction of DLCO (TLC/DLCO ratio > 1.5) suggests pulmonary hypertension.
- High resolution CAT scan is highly sensitivity and allows the detection of alveolitis (ground glass appearance) in early stages.
- Late CAT scan changes include severe fibrosis and traction bronchiectasis.
Systemic sclerosis: renal involvement
Renal involvement is considered to be the most deadly complication of SSc.
Renal crisis= develops in 15-20 percent of patients and usually occurs with an abrupt onset (within hours)
Malignant hypertension, acute cardiac failure, myocardial infarction, stroke, and rapidly progressive renal insufficiency characterize scleroderma renal crisis.
Progression to renal failure and death occurs rapidly unless the diagnosis of renal crisis is established and aggressive treatment instituted promptly.
Patients with diffuse and rapidly progressive skin involvement are at the highest risk.
Systemic sclerosis: Cardiac involvement
Heart involvement: 80% of patients
- clinically significant primary cardiac dysfunction is less common.
- Tachyarrythmias and cardiac conduction disturbances are frequent.
- Pericardial effusion is found by echocardiography in many patients, but symptomatic pericarditis is rare.
- Right heart strain in cases of pulmonary hypertension.
Systemic sclerosis: other visceral involvement
Peripheral neuropathy (trigeminal neuralgia and carpal tunnel syndrome) can occur but the CNS is spared. - Can cause some pain
Erectile dysfunction develops in many male patients, and can precede other SSc manifestations.
The sicca syndrome is frequently found (Secondary Sjögren’s Syndrome).
- Replacement of exocrine glands by fibrotic tissue
Hypothyroidism is detected in a third of the patients.
Primary biliary cirrhosis has been documented in a number of cases.
Laboratory findings in Systemic Sclerosis
The diagnosis is generally made on clinical grounds.
Laboratory data help in defining the type and extent of visceral involvement:
- ESR is usually normal.
- ANA test is positive in greater than 90% of patients and most characteristically speckled or nucleolar in diffuse form and anticentromere in limited form.
- No antibodies to native DNA, Sm and RNP
SSc-specific antibodies:
1. Anti-centromere antibodies > 80%
- Anti-Scl-70 antibody (anti-topoisomerase 1)= specific for SSc, present in 30-40% of patients
- Seen more commonly in severe interstitial lung disease
** Both anti-centromere and anti-Scl-70 antibodies helpful in classification of SSc subset (anti-centromere= limited disease, Anti-Scl-70= diffuse)
- Anti-RNA polymerase III antibodies: less common
- Seen in severe, diffuse disease, renal crisis
Diffuse vs Limited Cutaneous Systemic Sclerosis
Diffuse:
- Higher mortality
- Raynaud’s= earlier onset
- Truncal, acral skin sclerosis
- Early lung invovlement
- Renal crisis
- Cardiac fibrosis
- Anti-topoisomerase antibodies (Speckled/nucleolar (anti-Scl-70) antibodies)
- RARE to see anti-centromere antibodies
Limited Cutaneous Raynauds:
- Lower mortality,
- > 1 year to Raynaud’s onset
- Acral skin sclerosis
- Late lung involvement (pulmonary hypertension)
- Rare renal crisis
- Rare cardiac fibrosis
- Pattern of antibodies= anti-centromere (90%)
Course and prognosis of Systemic Sclerosis
The course of SSc is often characterized by progression.
- The highest mortality is seen in the first two-five years of the disease.
- The prognosis of SSc is related to the extent of visceral involvement:
- Limited SSc has low overall mortality.
- Diffuse SSc has a 50-60% mortality at 5 years.
A grave prognosis is closely correlated with the presence of renal, pulmonary and cardiac involvement.
Systemic Sclerosis: Pathogenesis
Three outstanding features responsible for the clinical and pathologic manifestations of SSc:
- Excessive deposition of collagen and other connective tissue macromolecules in skin and internal organs.
- The most prominent clinical manifestations and high mortality of SSc are caused by tissue fibrosis of the affected organs.
- The excessive collagen deposition in SSc is due to overproduction of this protein by fibroblasts.
- Alterations in the regulation of collagen gene expression may be induced by cytokines and growth factors released from the tissue-infiltrating inflammatory cells.
- Prominent role of TGF-b and SMAD pathway. - Vascular lesions of capillaries and small arteries.
- Endothelial cell dysfunction may be the initial event in SSc pathogenesis.
- The vascular abnormalities become apparent prior to the onset of tissue fibrosis.
- Severe fibroproliferative vasculopathy.
- Perivascular cellular infiltration with activated T-cells and macrophages. - Alterations of humoral and cellular immunity.
- Almost universal occurrence of anti-nuclear antibodies.
- Mononuclear cell infiltrates in affected tissues.
- Activation of innate immune response and Interferon signature.
- The mononuclear infiltrates are predominantly activated lymphocytes (helper T-cells) and macrophages.
- There is no evidence of autoantibody - mediated tissue injury in SSc.
Achondroplasia
Growth plate disorder
- Most common disease of growth plate
- Failure of norrmal epiphyseal plate cartilage
- Autosomal dominant; MOST are new mutations in: FGFR-3, CHR 4
Scurvy
Growth plate disorder
- Vitamin C deficiency affecting collagen synthesis
- Woven bone not formed
- Prominent calcified cartilage
Osteochondroma
Developmental defect (hamartoma) at epiphyseal plate
- “Ring of Ranvier”
- Cartilage capped growth growing away from joint
Hereditary multiple osteochondromatosis:
- Extra genes on Chromosomes 8, 11, 19–> chondrocyte proliferation and differentiation
Bone Fracture
Most common bone lesion. Types: 1. Spiral 2. Transverse 3. Compression Primary vs Secondary (due to tumor)
Complications:
- Soft tissue and nerve damage
- non-union
Fracture healing
- Inflammatory phase:
- 1-2 days: hemorrhage
- 2-5 days: neovascularization at periphery
- 7 days: early callus - Fracture healing:
- After 1st week: Reparative phase (repair from periphery to center of fracture)
- Weeks later: remodeling phase (cortex restore, callus ingrowth seals ends)–> can take years
Osteoarthritis
Most common form of joint disease
- Slow, progressive
- Seen in articular cartilage of weight bearing joints, fingers
- Older patients (or young following trauma)
- Primary osteoarthritis:
Unknown etiology; several postulated factors:
- increases with age
- 85% of patients age 75-79
- < 45 years= male predominant; > 55 years= females
- Hereditary factors? - Secondary osteoarthritis:
Known etiology
Clinical: See joint space narrowing, subchondral bone thickening, painful joint - Pain follows activity - Restriction of motion - Lab findings unhelpful - Supportive therapy
Pathology:
- Seen at DIP, PIP of upper extremity; knees, hips, cervical and lumbar spin
- Narrowing of joint space on x-ray
- Increased subcondral bone, bone cysts
- Osteophyte formation
Histology:
- Earliest= death of articular cartilage
- Cracking, fibrillation
- Reactive bone/cartilage–> fibrocartilage plug
- Eburnation (loss of articular cartilage), subchondral bone cyst (decreased density on x-ray), osteophyte (dense bone formation with cartilage cap, continuous marrow)
