Musculoskeletal Flashcards

Question

Rheumatology

Answer 1

``` Incorporates Inflammatory states: - Autoimmune (RA, SLE, Vasculitides) - Autoinflammatory (Gout, Juvenile RA, TRAPS, FMF) Non-inflammatory musculoskeletal states: - Degenerative disease (osteoarthritis) ```

Answer 2

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: 2. Phagocytes, NK-cells, dendritic cells, epithelial surfaces, non-antibody molecules (activated cells) 3. B cells (adaptive) and T cells (adaptive)

Answer 3

- Express Toll-like receptors (TLR) in their surface - Internalizes and presents antigens - Secrete co-stimulatory molecules (CD80, CD86) - Secrete cytokines: regulate process

Answer 4

- 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

Answer 5

- 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

Answer 6

``` 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 ```

Answer 7

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

Answer 8

1. Immunization with self-antigens in presence of adaptive immune system stimulants (adjuvants) 2. Etiology: Genetics, sex/sex hormones, environmental triggers See: 1. self-antigen recognition by lymphocytes 2. autoantibody production 3. tissue damage

Answer 9

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)

Answer 10

Strong female predominance in SLE (F:M 9:1 ratio) due to: 1. Dose effect of X chromosome: 2 X chromosomes confer higher risk than 1 X, independently of sex hormones 2. Hormone (estrogen and prolactin) effect on survival and activation of T and B lymphocytes antigen presentation and autoantibody production

Answer 11

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

Answer 12

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

Answer 13

Antibody-mediated: 1. Injury from anti-tissue antibody - Leads to tissue injury 2. Injury from immune complex deposition Cell-mediated tissue damage: 1. Central and peripheral T-cell tolerance defects 2. 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 3. 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)

Answer 14

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

Answer 15

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

Answer 16

- 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%

Answer 17

- 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

Answer 18

The most common non-neoplastic lesion of salivary glands - “Pooling of mucin in a cystic cavity” Types: 1. Retention type – mucin pooling confined within a dilated excretory duct 2. 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

Answer 19

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

Answer 20

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: 1. Systemic: collagen vascular disease 2. 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

Answer 21

1. Acute: - Haemophilus, Branchamella 2. Allergic: - Hypersensitivity reaction to fungal antigens (atopic patients), aspergillus 3. Fungus ball (mycetoma, aspergilloma) - Sinuses with poor drainage; fungi proliferate and form dense mass of hyphae - DO NOT invade mucosa/vessels 4. 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

Answer 22

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)

Answer 23

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

Answer 24

- 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

Answer 25

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

Answer 26

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

Answer 27

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

Answer 28

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

Answer 29

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)

Answer 30

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 (1-10 mg/dL) - Autoimmune diseases (Most connective tissue diseases, Rheumatoid arthritis) - Myocardial infarction - Malignancies - Pancreatitis - Mucosal infection (bronchitis, cystitis) Marked Elevation (>10 mg/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)

Answer 31

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

Answer 32

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)

Answer 33

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)

Answer 34

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)

Answer 35

1. 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 2. 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) 3. Anti-dsDNA: - Antibodies to nuclear, dsDNA - 60-70% specific to SLE 4. Anti-centromere antibodies: limited to scleroderma (CREST) 5. Anti-Scl-70 antibodies (topoisomerase I): 90% specific, not sensitive for scleroderma 6. Anti-histone antibodies: 95% specific for drug-induced lupus

Answer 36

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: 1. Anti-cariolipin antibodies (IgG, IgM, IgA) - Detected by ELISA 2. Beta 2 glycoprotein I (B2GPI) antibodies: - Directed against phospholipid-binding plasma protein - Detected by immunoassays 3. Lupus anticoagulant - Tests for Inhibitor of phospholipid-dependent clotting

Answer 37

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)

Answer 38

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.

Answer 39

Relatively common disorder - Affects >1% of the population of North America - Female:male 2.5:1 - Incidence increases with age (Peak: 4th-6th decade)

Answer 40

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

Answer 41

``` 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!

Answer 42

Joint involvement at time of onset: 1. Polyarticular (75%) - Small joints of hands and feet (DIP joints) - Large joints 2. 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

Answer 43

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)

Answer 44

``` 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)

Answer 45

- detectable already years before the first clinical symptoms - also predictive for the level of erosiveness APCA detection in clinical practice: 1. Effect of Smoking - Earlier, worse arthritis in ACPA+ smokers 2. Differentiate RA from arthritis in HCV infection - positive RF 12/14pt, negative aCCP--> probably arthritis, not RA 3. Predict erosive and progressive disease - Combination of anti-CCP and IgM RF

Answer 46

1. Object is to confirm the presence of a systemic inflammatory process 2. Evaluate for serious major organ involvement 3. Check for pertinent but unusual causes of systemic polyarthritis Labs: 1. CBC: anemia, nL or slightly elevated WBC, and/or platelet 2. ESR elevation 3. CRP elevation 4. BUN, creatinine 5. Liver enzymes 6. ANA (not usually positive) 7. 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

Answer 47

``` 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

Answer 48

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

Answer 49

``` Subcutaneous Nodules Vasculitis - Arterioles, capillaries, venules - Mostly leukocytoclastic vasculitis - Skin ulcerations (necrotizing) ``` Nervous system: 1. Myelopathy 2. 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 3. 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

Answer 50

Goal is complete remission 1. Start with anti-inflammatory medications - NSAIDs - Corticosteroids 2. Add immunomodulators (DMARDs) early 3. If no significant improvement in first few months add “biologics” - Antibodies against inflammatory cytokines

Answer 51

Rheumatologic emergency: - Urgent- investigate thoroughly Diagnostic possibilities: 1. Infections - Bacterial (most destructive) - Viral - Fungal 2. Crystals - Monosodium urate (MSU) (Gout) - Calcium pyrophosphate (CPPD) - Apatite 3. Hemorrhagic 4. Tumors - Villonodular synovitis - Malignancy 5. Vascular - Sickle cell disease - Osteonecrosis 6. Other - Hemarthrosis - Systemic inflammatory arthritis Diagnostic techniques: 1. Aspirate Joint 2. Synovial fluid examination: - Cell count - Gram Stain - Culture and sensitivity - Light microscopy - Polarized microscopy

Answer 52

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

Answer 53

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: 1. Hematogenous spread (most common) 2. Contiguous spread 3. Soft tissue-skin infection 4. Penetrating trauma 5. Surgery 6. Adjacent osteomyelitis 7. 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

Answer 54

``` Acute severe pain Swelling Increase in joint temperature Fever (+/-) Systemic toxicity (chills etc +/-) ``` Site: 1. Knee > large diarthrodial joints 2. In children: knee and hip 3. IV drug users: axial (sternoclavicular, SIJ) - Methicillin resistant S. aureus - Serratia - Ps. aeruginosa

Answer 55

1. 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%) 2. Blood culture: 50% + in non-GC arthritis 3. Increased WBC with left shift 4. 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!

Answer 56

Cause: disseminated GC infection in immunocompetent 60,000/mm2 - Outcome: favorable

Answer 57

Very common type of arthritis - Starts monoarticular (Gout, pseudo-gout) Associated findings: 1. Gout: - HTN, - hyperuricemia, - EtOH, - male (post-menopausal females) 2. CPPD (pseudo-gout)= Calcium pyrophosphate dihydrate disease - Older age, - DJD (degenerative joint disease), - chondrocaclinosis (calcium in cartilage) on x-ray

Answer 58

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

Answer 59

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

Answer 60

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: 1. Acute phase - Soft tissue swelling 2. Chronic - Oval, round periarticular or intraarticular erosion (bite-out) - Sclerotic margin - Joint space is preserved until late

Answer 61

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: 1. chondrocalcinosis: Calcium deposition in cartilage (may be asymptomatic) 2. Pseudo-gout (symptomatic) 3. Pseudo-osteoarthritis 4. Pseudo-rheumatoid arthritis 5. 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.

Answer 62

- 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

Answer 63

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 ```

Answer 64

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.

Answer 65

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

Answer 66

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.

Answer 67

1. 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. 2. Gastric/esophageal dilation 3. Watermelon stomach= Gastric Antral Vascular Ectasia (GAVE) with painless severe GI bleeding 4. Disordered motility: - Gastric distension - Bacterial overgrowth, diarrhea, malabsorption, pseudo-obstruction - Colonic disease with wide-mouth sacculation (pseudodiverticula)

Answer 68

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.

Answer 69

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.

Answer 70

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.

Answer 71

``` 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.

Answer 72

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% 2. 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) 3. Anti-RNA polymerase III antibodies: less common - Seen in severe, diffuse disease, renal crisis

Answer 73

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%)

Answer 74

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.

Answer 75

Three outstanding features responsible for the clinical and pathologic manifestations of SSc: 1. 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. 2. 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. 3. 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.

Answer 76

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

Answer 77

Growth plate disorder - Vitamin C deficiency affecting collagen synthesis - Woven bone not formed - Prominent calcified cartilage

Answer 78

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

Answer 79

``` 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

Answer 80

1. Inflammatory phase: - 1-2 days: hemorrhage - 2-5 days: neovascularization at periphery - 7 days: early callus 2. 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

Answer 81

Most common form of joint disease - Slow, progressive - Seen in articular cartilage of weight bearing joints, fingers - Older patients (or young following trauma) 1. 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? 2. 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)

Answer 82

Pathophys: 1. Loss of ratio of short to long chains in aggrecan molecules - Short chain= Keratin sulfate - Long chain= chondroitin sulfate Aging= Increased keratin (short chain), decreased chondroitin (long chain) 2. Cellular changes: chondrocyte loss (apoptosis, necrosis)--> decrease in T2 cartilage 3. Develop osteophytes (outgrowth of edge of vertebrae), herniation of discs High risk populations: 1. Smoking 2. Obesity 3. Heavy laborers: repetitive axial loading, prolonged driving (vibration), repetitive bending, twisting

Answer 83

Presentation: 1. Axial or radicular pain 2. Neurologic impairment 3. Radiographic instability: scoliosis, spondylolisthesis

Answer 84

Constitutional symptoms 1. Progressive, unrelenting pain (non-mechanical) 2. Worse at night, at rest 3. Fever, chills, sweats 4. Anorexia with weight loss, fatigue Neurological symptoms: 1. Progressive weakness 2. Acute dexterity / balance changes 3. Bladder dysfunction 4. Cervical myelopathy: loss of dexterity, coordination; impaired balance/gait May indicate: - infection - Cancer - Myelopathy - Severe nerve compression

Answer 85

Clinical presentation: - Severe leg pain - Saddle anesthesia (perineum, perianal) - Altered bladder function (retention)

Answer 86

Exert tension on nerve roots to see where pain radiates Cervical radiculopathy: - Frozen shoulder - Carpal tunnel - Cubital tunnel - Subacromial bursitis - TOS Lumbar radiculopathy: - radiating pain; leg > back - motor / sensory - compressed nerve - depressed reflex - compressed nerve - no pathological reflexes

Answer 87

Pathological reflexes: 1. Babinski's sign 2. Hoffman's sign 3. Ankle clonus 4. Hyperreflexia

Answer 88

Confirms clinical impression - After failure of non-operative treatment - Setting of "red flags" 1. Plain radiographs (orthogonal views) - looking for issues with bones 2. MRI or CT scan/myelogram

Answer 89

Spinal fluid= white Dark= Low intensity - Spinal disc= dark, impinges on white spinal fluid - Should have some white in discs (fluid-filled)- degenerative disc disease may see loss of lightness

Answer 90

``` “Clinical Diagnosis” Most improve < 6 weeks Stepwise treatment algorithm Surgical treatment - rarely necessary - “last resort” when indicated ``` Natural history: 90% better < 6 weeks “other 10%” = 90% of costs Time dependent likelihood of improvement >6 weeks symptoms--> 20% improvement >12 weeks symptoms-->10% improvement Compensation > 6 months -->never return to work Medical managment: - Short course rest - Nonsteroidals and acetaminophen - Physical therapy - Oral steroids (prednisone taper)? - Muscle relaxants?? - AVOID NARCOTICS! Physical therapy, education, strengthening, conditioning - AVOID BEDREST!

Answer 91

1. Initial: - Collar/Brace - NSAIDS - Traction - Physical Therapy - Injections 2. Surgery: - For recalcitrant symptoms (4-6 weeks) - Neurologic deficit, correlative imaging - Signs of spinal cord compression

Answer 92

"shopping cart sign" - Pain relieved by leaning forward while walking Commonly seen in patients > 60 years - Bilateral - Structurally abnormal spine - "Claudication"- not enough room for nerves

Answer 93

``` “Slip of the vertebra” Isthmic (crack in ring) - 5% of population - not prognostic Degenerative - F > M, over 40 yrs - with spinal stenosis ```

Answer 94

Clinical syndrome Spinal cord problem with NO PAIN - 70% worsen with time - IF they have functional problem, get imaging ASAP See recurrent falls, ataxia Treatment: progressive worsening--> early surgery referral * Success of Surgical Decompression: - Length of symptoms - Age - Medical status

Answer 95

Neck Pain--> Degenerative Disk Disease 1. Try Exercise, Therapy, Chiro, Medications Arm Pain --> Pinched Nerve 1. Try Exercise, Therapy, Chiro, Medications 2. Surgeon If Not Improved, Worsening, Weakness Fine Finger Movement, Balance, Bladder --> Spinal Cord Compression 1. Speak With Surgeon Early

Answer 96

Back Pain --> Disk Degeneration 1. Try Nonsurgical Treatment Leg Pain --> Pinched Nerve 1. Try Exercise, Therapy, Chiro, Medications 2. Surgeon If Not Improved, Worsening, Weakness Bowel/Bladder Problem --> Cauda Equina Syndrome 1. Surgeon

Answer 97

``` Female with age > 65 (vertebral fracture 8:1 F:M ratio; hip 2:1) - 15% hip fractured by 80, 25% by 90 years Previous fracture Family history of hip fracture Low body weight (less than 125 lbs) Cigarette smoking Excess alcohol intake Non-Hispanic white women and Asian women ```

Answer 98

``` Prolonged immobilization Low dietary intake of calcium, phosphorus, and Vitamin D Late menarche Early menopause High levels of caffeine ingestion Obesity Low level of physical activity ```

Answer 99

Endocrine disorders: - Acromegaly, Cushing’s syndrome, Eating disorders, Hyperparathyroidism, Hyperthyroidism, Hypogonadism, Hyperprolactinemia Gastrointestinal disease - Celiac disease, Gastrectomy, Inflammatory bowel disease, Jejunoileal bypass, Gastric bypass surgery, malabsorption, pancreatic insufficiency, TPN Marrow related disorders Organ transplantation Idiopathic hypercalciuria, hypophosphatasia… Renal dysfunction

Answer 100

``` Anti-convulsants (Dilantin) Certain cancer chemotherapy medications Glucocorticoids Lithium Cyclosporine Heparin Thyroxine ```

Answer 101

National Osteoporosis Foundation: 1. History of hip or vertebral fracture 2. T score less than -2.5 w/o secondary cause 3. T score between -1 and -2.5 at femoral neck, hip, and spine with a high risk factor FRAX assessment tool (WHO) - Integrates clinical risk factors and BMD

Answer 102

Diet replete with calcium and vitamin D: 1. Premenopausal women should consume ~1000 mg of calcium daily (total diet plus supplement) 2. Postmenopausal women should consume ~1200 mg of calcium daily (total diet plus supplement) 3. 800 international units of Vitamin D per day

Answer 103

Diet replete with calcium and vitamin D: 1. Premenopausal women should consume ~1000 mg of calcium daily (total diet plus supplement) 2. Postmenopausal women should consume ~1200 mg of calcium daily (total diet plus supplement) 3. 800 international units of Vitamin D per day

Answer 104

Bohan and Peter classification (4/5 criteria) 1. Symmetric proximal muscle weakness 2. Elevated serum levels of muscle enzymes 3. Myopathic changes on electromyography 4. Characteristic muscle biopsy findings 5. Appearance of a distinct rash * Can also have myositis as part of other connective tissue disease/overlap syndrome Demographics: - Can be found in children and adults - Incidence is higher in African-Americans (3:1) and females (2:1) - Is rare with 2 to 10 new cases per million per year - Patients report a symmetric proximal limb weakness that is often painless and has a subacute onset - Patients may have trouble combing hair, rising from a chair - May be associated with malignancy (DM>PM) - Dermatomyositis has pathognomic skin rashes Diagnosis: - Elevated muscle enzyme levels such as: Creatinine Kinase (CPK), Aldolase, Lactate Dehydrogenase (LDH), Aspartate Aminotransferase (AST) and/or Alanine Aminotransferase (ALT) Autoantibodies are detected in ~50% of patients 1. Myositis specific antibodies directed against amino-acyl tRNA synthetases (Jo-1, EJ, OJ…) often associated with Anti-synthetase syndrome 2. Myositis specific antibodies such as SRP, Mi-2 3. Myositis associated antibodies (PM-scl, SSA) Treatment: - Corticosteroids - Methotrexate, azathioprine, IVIG, mycophenylate mofetil

Answer 105

Infiltrate of CD8+ cells around normal myofiber - Inflammation localized to endomysium - Anti-Ro Jo-1, PMScl

Answer 106

Infiltrate of CD4+ cells in myofiber - Inflammation in perivascular areas of perimysium - Atrophy of fascicles

Answer 107

Is classified under inflammatory myopathies but it is unknown if it is auto-immune Demographics: Patients > 50 years, M > F Symptoms: Weakness is distal and can be assymetric Labs: CPK is usually less than PM/DM Treatment: It responds poorly to corticosteroids Hisopath: - Vacuolated muscle fibers, muscle fiber inclusions, paired helical fibers by EM

Answer 108

Chrondroblastoma | Giant cell tumor

Answer 109

``` Osteoblastoma Osteochondroma Non-ossifying fibroma Osteoid carcinoma Chrondromyoid fibroma Giant cell tumor ```

Answer 110

Enchondroma | Fibrous dysplasia

Answer 111

Ewing sarcoma | Chondrosarcoma

Answer 112

Osteosarcoma | Jusxtacortical osteosarcoma

Answer 113

Developmental abnormality Path: activating mutation in alpha subunit of guanine nucleotide binding protein--> increased cAMP X-ray: lucent ground glass quality, well-marginated borders Histo: disorganized fibrous and osseous elements - Irregular trabecular bone within fibrous stroma, no osteoblastic component 1. Monostotic: - Most common (75-80%) - 2nd to 3rd decade, M=F - Sites: proximal femur, tibia, ribs, facial bones - Asymptomatic or pathologic fractures 2. Polyostotic: - 25%, 1/2 skeleton - Childhood, F > M - Pathologic fractures - Pregnancy may stimulate growth 3. McCune Albright: - FD + endocrine, skin, sarcoma (< 1%) Treatment: curettage, fracture repair

Answer 114

AKA: Fibrous cortical defect - Common (25-40%, 4-10 years old) - Sites: tibia, femur - Neoplastic vs developmental - May see fratures X-ray: cortical, scalloped, eccentric Histo: spindle cells with multinucleated giant cells, macrophages

Answer 115

Unilocular, fluid-filled, non neoplastic cyst - Disturbance of bone growth with trauma - Kids/adolescents, M > F (3:1) - 2/3 upper humerus, femur - Metaphyseal, adjacent to growth plate X-ray: demacated Histo: thin, fibrous cyst wall Clinical: fracture, usually asymptomatic

Answer 116

Expansive, hyperemic (blood filled sponge) - Kids, adolescents - Periosteum around lesion thin but intact Histo: granulation tissue, mononucleated giant cells and osteoid trabeculae May represent cystic degeneration of underlying lesion Treatment: curettage (remove entire segment due to risk of osteosarcoma underlying hemorrhage

Answer 117

Small, painful benign lesion - M > F (3:1), 5-25 years - Cortical, usually metaphysis; diaphysis of lower extremity long bones Clinical: pain, worse at night, relieved by ASA X-ray: sclerotic cortical lesion Histo: nidus composed of thin trabecular bone, granulation tissue background - Numerous osteoclasts, osteoblasts Treatment: curettage, radiofrequency, electrocautery, mini bloc excision

Answer 118

Histo: similar to osteoid osteoma but larger - M=F, 10-25 years - NOT accompanied by sharp pain Sites: mainly spine, long bones Imaging shows benign process: encapsulated, no inflammatory reaction

Answer 119

Intraosseous tumor - Well-differentiated cartilage - Any age, asymptomatic - Removal only due to concern of well-differentiated osteosarcoma Site: metacarpals, phalanges - Hands/ feet X-ray: well delineated, lytic Histo: increased cellularity, atypia Treatment: curettage if painful or causing fractures

Answer 120

Uncommon epiphyseal tumor - 2nd-3rd decade, M > F Sites: femur, tibia, humerus X-ray: lytic, eccentric Histo: chondroblasts, mineralized matrix, multinucleated giant cells; "Chicken wire" matrix

Answer 121

Most common PRIMARY malignant bone-forming tumor (most common bone tumor= metastatic) - 2nd decade, M > F - Rb gene mutation in 2/3; p53 Sites: metaphysis of femur, tibia > humerus X-ray: lytic, sunburst pattern, codman's triangle Clinical: Pain, increased alk phos Histo: woven bone (osteoid) with malignant osteoblasts Variants: - Parosteal - Periosteal - Telangiectatic

Answer 122

2nd most common primary malignant bone tumor - M > F, 4th-6th decade - Some from cartilage enchondromas - Variants classified by location - Can see molecular trisomy 7, rearrangement of chrom 17 * extracellular sarcoma mixoid type: (9;22)(q31;q12) Sites: - Axial, proximal femur, humerus X-ray: lucent or ring-like Histo: grading based on cellularity, degree of atypia

Answer 123

Uncommon - 2/3 < 20 years, M > F (2:1) - Reciprocal translocation t(11;22)(p13;q12), PNET family Clinical: pain, swelling X-ray: midshaft/diaphysis of long bones; "onion skin pattern" Histo: small round blue cell tumor - PAS, CD99 - t(11;22) or t(21;22) Treatment: - Chemo/radiation - surgery - 60-75% 5-year recurrence rate

Answer 124

Locally aggressive - 3-4th decard; F > M, Asians - Site: epiphysis, metaphysis of long bones Clinical: pain, path fractures X-ray: lytic, multilobulated "soap bubble" Gross: Blood-filled sponge Histo: mononuclear and mononucleated giant cell tumors Treatment: curettage, recur (50%), 10-15% lung mets

Answer 125

Malignant plasma cells - M > F, 65 years - Sites: skull, spine, ribs, pelvis, femur X-ray: lytic Plasmacytoma= Multiple myeloma= Histo: sheets of plasma cells Diagnosis: - Protein electrophoresis Treatment: radiation, chemo - MM: Poor prognosis (32 months) - Plasmacytoma: 65% 5-year survival

Answer 126

Most common malignant tumor of bone Most are carcinomas Sites: vertebrae x-ray: lytic, blastic Origin: Prostate, breast, kidney, thyroid, lung Treatment: surgery, chemo, radiation - Prognosis: represents advanced cancer stage

Answer 127

Benign, fast-growing tumor - adults - Site: extensor surfaces Etiology: trauma-induced reactive proliferation Histo: active fibroblastic lesion Treatment: excision

Answer 128

Slow-growing, locally aggressive - Increased incidence in diabetics, alcoholics, epileptics - May recur after excision - Palmar (1-2%), plantar Histo: bland spindle cells

Answer 129

Malignant fibroblastic tumor - Adults: seen in thigh, knee - Congenital form= t(12;15) - Firm mass Histo: cellular fibroblastic proliferation with varying atypia - Pleomorphic, hypercellular - "herringbone pattern" Treatment: surgical Prognosis: 40% 5-year, directly related to differentiation

Answer 130

Malignant fibrous histiocytoma - Most COMMON soft tissue tumor - seen in older adults Sites: deep fascia, skeletal muscle Histo: pleomorphic, storioform Prognosis: dependent on cytologic atypia - 50% recur - Lung metastases

Answer 131

Most common benign soft tissue mass - Sites: subcutaneous tissue, upper half of body Gross: yellow, soft, lobulated Histo: mature adipocytes Treatment: simple excision * Deeper: harder to differentiated from liposarcoma

Answer 132

2nd most common sarcoma - Adults, > 50 years - Slow-growing, may be large (thigh, retroperitoneum) Histologic subtypes: - Myxoid variant: t(12;16)(q13,p11) Prognosis: dependent on subtype (round cell type- < 20% 5 year survival)

Answer 133

Benign smooth muscle tumor - Extrauterine: subcutaneous tissue - May be painful Histo: bland spindle cells, low mitotic rate Treatment: simple excision

Answer 134

Seen in extremities, BV wall - Larger with necrosis, cystic degeneration Histo: fascicles of spindle cells with varying atypia, mitotic rates Prognosis: majority eventually metastasize

Answer 135

Striated muscle differentiation - Most common soft tissue sarcoma in children HIsto: 5 types: prognosis best--> worst 1. Botryoid embryonal: best prognosis 2. Spindle 3. Embryonal 4. Alveolar 5. Undifferentiated Treatment: combined therapy Prognosis: 80% 5-year

Answer 136

Arises in joint; highly malignant - 10% soft tissue sarcomas - Seen in adolescents, young adults - Painful, tender mass Histo: bi- or mono-phasic 60% recur; lung metastases Prognosis: 50% at 5 years

Answer 137

Marble bone disease: Albers-Schonberg disease - Group of rare, heritable disorders; increased skeletal mass due to abnormally dense bone Autosomal recessive= severe, fatal to infants - Marked anemia, cranial nerve entrapment, hydrocephalus, infection Autosomal dominant= mild anemia/ asymptomatic Pathogenesis: - Failed osteoclastic bone resorption - Mutation in osteoclast formation/function genes - Defect in acidification of bone - Mutations: TCIRG1 (AD- proton pump); CLCN7 (AR- Chloride channel), Carbonic anhydrase II (AR); transciption factors, cytokines causing osteoclast differentiation - Primary spongiosum remains--> cartilage cores, thickened cortex, lack of funnelization of metaphysis

Answer 138

Short, block-like radiodense bones on x-ray/CT - Radiopaque, 2-3 times normal weight - WEAK bone due to disorganized structure (can't remodel with stress) - Calcified cartilage= weak, friable Anemia due to replacement of marrow by sheets of osteoclasts, marrow fibrosis - Extramedullary hematopoeisis - Pancytopenia Blindness, deafness (foramen entraps nerves) Treatment: bone marrow transplant, human IFN-gamma

Answer 139

AD mutation in Type 1 collagen gene (Chr 17,7)--> delayed maturation of bone, joints, ears, ligaments, teeth, skin (7 types) OI1= mildest form, blue sclerae - Fractures after birth - Exuberant callus formation (tumor-like) - Ossicles fuse--> deafness (age 20-30) - Normal stature OI2= lethal prenatal form - Marked short stature, limb deformities - Crushed in utero OI3= progressive, most severe type - multiple fractures present at brith - AD (rare AR) - Severely short stature OI4= similar to OI1 with normal sclera - Cortical bone woven--> eventually matures - Aggressively treated to prevent dwarfism

Answer 140

Mutations of Col1A1 (all OI), Col1A2 (OI 2, 3, 4) on chrom 17, 7 - Point mutation of glycine residue most common in OI - Col1A2 mutation seen in 1/2 synthesized collagen molecules- variable phenotypes

Answer 141

Bone, marrow death; more common in children Multiple causes: - Trauma - Emboli - Systemic disease - Steroids - Bisphosphonates Necrotic bone: stress fracture and compaction over time--> fracture of rigid articular cartilage and subchondral bone

Answer 142

Avascular necrosis of femoral head in children - Necrosis and remodeling--> collapse of subchondral bone, incongruous articular surface - May cause severe arthritis Femoral head in kids depends in lateral epiphyseal vessels susceptible to trauma, intrarticular pressure

Answer 143

Infection of bone (usually bacterial: staph, strep, haemophilus, salmonella) and marrow - Direct penetration (trauma) or hematogenous - Can also cross cartilage, infect joint spaces Hematogenous: kids 5-15 years- may see fever, localized pain, etc - Can also be seen in drug addicts X-ray to diagnose aggressive process Pathogenesis: - Unique blood supply at metaphyseal area--> slowing of blood - Bacterua penetrate wall--> infection - Increased pressure--> compromised blood supply--> necrosis--> more bacteria - Access to cortex, periosteum, joint, skin (claoca) - Sequestrum= dead cortical bone - Involucrum= new bone formation around dead bone - Brodie abscess= sequestrum within pus In vertebral bodes: disc are NOT barrier for spread - Enterics, staph--> attract inflammatory cells--> collagenase--> move to other cells - Complications: vertebral body collapse, spinal epidural abscess, cord compression - Vertebral body collapse, neurologic defects Complications: - Septicemia - Acute bacterial arthritis (joint space) - Pathologic fracture - Squamous cell carcinoma (chronic infection) - Amyloidosis (chronic infection) - Chronic osteomyelitis

Answer 144

Changes from acute inflammatory process--> chronic - See plasma cells, lymphocytes - Due to failure to resolve acute osteomyelitis ** Differentiate from myeloma, cytoma (plasma cell)- run immunohistochemical stains for light chains (polyclonal vs monoclonal) Marrow fibrosis--> fibrosseous lesion Treatment: - Surgical debridement; long term antibiotics

Answer 145

From focus elsewhere - Affects vertebral bodies; spares lamina, spines (Pott's disease) - Thoracic vertebrae (t-11> cervical or lumbar) - Leads to collapse of vertebral body - Can track down anterior soft tissue, spinal ligaments--> moves into pelvis, inguinal region (Cold abscess= psoas abscess) ``` Path: Caseating granulomatous inflammation - Slow resorption of bone - Little or no woven bone--> collapse - Special stains (AFB- organisms visible), look for sarcoid, fungi ```

Answer 146

Primary= more common 1. Type 1= post-menopausal; absolute increase in osteoclast activity due to estrogen withdrawal 2. Type 2= > 70 years, attenuated osteoblast function (no increase in osteoclast activity) Secondary osteoporosis: Associated with other conditions: - Endocrine (Cushing's, hyperthyroidism, hypogonadism, iatrogenic steroids--> inhibited osteoblasts) - Hematologic malignancies (Multiple myeloma--> activates osteoclasts - Malabsorption (decreased Ca, Ph, Vit D) - Alcoholism--> directly inhibits osteoblasts

Answer 147

Increased PTH--> bone resorption - Early= line of osteoclasts--> flare lesions 1. osteitis fibrosa (osteoclast stimulation--> marrow fibrosis) 2. osteitis fibrosa cystica - -> brown tumor (hemosiderin deposition) : late stage - Subperiosteal bone resorption

Answer 148

Inadequate bone mineralization of newly formed bone, cartilage matrix - Adults and kids--> osteopenia Causes: - abnormal Vit D metabolism - Intestinal malabsorption - Renal disorders - Phosphate deficiency - mineralization defects Path: - pseudofractures - Exaggerated osteoid seams (osteoclast activity can't occur, delayed calcification)

Answer 149

Chronic condition: bone enlargement and lytic lesions (disordered remodeling) - uncoupling osteoblast/osteoclast activity - See clast only activity, or blastic activity with patchy clast activity--> mosaic bone - Seen in M & F > 60 years (3-4% in certain populations) - Solitary or multiple sites Pathogenesis: hereditary AD (chr 18) - Sequestosome 1--> p62 protein in RANK pathway (more aggressive form) - Viral nuclear inclusions similar to SSE (subacute sclerosing encephalitis)- giant cell tumor of bone Path: - "Hot" osteoclastic stage= lytic - Mixed stage - "cold" burnout stage: little activity Histo: - Prominent cement lines ("mosaic") - Osteoclast= pathologic cell; "killer clasts" with 50+ nuclei (vs normal 8) - Can see sarcomatous change in < 1% (adult type of osteosarcoma)

Answer 150

Pain (focal feature) - Skull involvement (frontal/parietal) - Pagetic steal--> light headedness (calvareal bone is stealing blood supply) - Fractures/ arthritis - High output cardiac failure (significant part of skeleton involved--> increased cardiac demands) - Sarcomatous change, osteosarcoma in older patients (< 1%)

Answer 151

NOT inflammatory process "Wear and tear" loss of cartilage Cartilage breaks down, retains water--> thinning, cracking--> narrow joint space - Versus just aging--> decreased cartilage water content Osteophytes (cysts), subchondral cysts, sclerosis Joint: synovitis, inflammation, stiffness/grinding--> pain

Answer 152

``` One cause of osteoarthritis- cumulative stress of weight and muscle force on joints. Examples (on knees): - Walking= 2.5 times body weight - Jogging= 4.5x body weight - Running= 5.5 x body weight - Stairs = 7x body weight ```

Answer 153

Risk factors: - Female - Obese - Prior joint injury - Family history

Answer 154

``` Appearance ROM (limited, may have contractures) Tenderness Stability Crepitus (grinding) Maneuvers (Patricks: abduct hip) Neurovascular status (maybe claudication is causing pain) - Examine above and below site: hip may be causing knee pain Varus vs valgus alignment Should have no erythema, may be warm ```

Answer 155

1. Radiographs (weight-bearing X-ray) - Joint space narrowing - Subchondral cysts - Bony sclerosis - Osteophyte formation ** Severity of x-rays and clinical symptoms do NOT always correlate 2. NO lab tests 3. MRI can show arthritis, but x-ray best

Answer 156

Alleviate pain, restore function Non-operative treatment: - Patient controlled (weight loss, activities) - Physician controlled (meds- NSAIDs, supplements- glucosamine, chondroitin, PT/braces, injections- next step!) * injections: 1. Corisone (should last up to 6 months) 2. hyaluronic acid (synvisc) supplementation (after cortisone not effective)

Answer 157

Surgery: - Failed conservative management - Severe, intolerable pain - Unable to perform activities of daily living - Diminished quality of life - Age limitations: not many, usually health Surgical options: - Debridement (only effective in elbow) - Osteotomy (younger pts with one-sided degeneration) - Arthrodesis (fusion- rare except in low back) - Resection (may be seen after series of infection- seen at base of thumb= 2nd most common arthritis site after knee) - Replacement: 1. Hemiarthroplasty 2. Unicondylar 3. Patellofemoral Or TOTAL Total joint replacement complications: - Infection - Bleeding - DVT, PE - Hip dislocation - Periprosthetic fracture - Neurovascular

Answer 158

Proinflammatory: 1. TNF-alpha 2. IL-1 3. IL-6 Anti-inflammatory 1. IL-6 receptor antagonists 2. IL-1 receptor antagonists 3. IL-10 4. Soluble TNF-receptor

Answer 159

1930s: - Gold 1950s: - Cortisone - Antimalarials - Immunosuppressants 1960s: - Sulfasalazine (also used in IBD) - Penicillamine (narrow therapy window) 1980s: - Methotrexate 1990s: age of biologics (change in approach to treatment) - Leflunomide - Etanercept - Infliximab - Anakinra 1990s: emphasis on treatment of symptoms, limiting joint destruction; use of DMARDs in higher doses, earlier use 2004 on: use biologic monotherapy earlier, biologic with methotrexate - When patient fails targeted therapy, switch therapy (monitor every three months)

Answer 160

Low disease acitivity: Non-biologics for 6-24 months Moderate: - Features of good prognosis: non-biologics - Poor prognostic features (high RA factore, bone erosions, etc.): Anti-TNF High disease features: - Anti-TNF

Answer 161

100% filtered at glomerulus - 98% reabsorbed in PCT - 40-50% secreted and reabsorbed - 8-12% excreted Overproduction of uric acid: - Inherited enzyme disorders - Myeloproliferative disorders (P. vera, hemolytic anemia, lymphoproliferative disorders, malignancies, psoriasis, obesity) - Drugs (ethanol= beer, cytotoxic drugs) - Diet (Shellfish) * alcohol decreases uric acid excretion, increases uric acid production Underexcretion of uric acid: - Chronic renal failure - Lead nephropathy - Dehydration - Starvation - Drugs (diuretics, alcohol, low dose aspirin, cyclsporine, tacrolimus, niacin, ethambutol, pyrazinamide

Answer 162

Stage 1= asymptomatic - Serum urate > 6.8 mg/dL - Not indication for treatment - Look for cause, associated conditions Stage 2= acute gouty arthritis, intercritical gout - Frequent attacks: prophylax to keep uric acid low - Infrequent attacks: treat symptoms - Tx for acute gout: 1. NSAIDs 2. Oral cochicine 3. Systemic glucocorticoids (hospital use) 4. Intra-articular glucocorticosteroids 5. Off-label: synthetic ACTH, IL-1 antagonism (anakinra) Stage 3= chronic gouty arthritis: - Tophi on physical exam - Chronic degenerative arthritis - Indications for drugs: 1. Frequent attacks ( > 2/year 2. Visible/radiographyically detected tophi 3. Defined uric acid overproduction 4. History of urolithiasis 5. Difficult to treat attacks due to polyarticular gout, CKD, CHF, major organ transplant

Answer 163

Chronic inflammatory disease either axial symptoms of spine and sacroiliac joints or predominantly peripheral SpA - Rheumatoid Factor negative (seronegative) - Associated with human leukocyte antigen HLA-B27 - Characterized by inflammation around enthesis (site of ligament insertion into bone) - Affect young M:F 4:1 adults with peak age of onset between 15 and 45 years - Multisystem chronic inflammatory diseases Can be associated with: - Uveitis - Psoriatic arthritis - Psoriasis - Reactive arthritis - IBD - Arthritis associated with UC/Crohn Can see SpA on MRI (non-radiographic) or x-ray

Answer 164

Predominantly axial: - Non-radiographic axial SpA - Ankylosing spondylitis Predominantly peripheral: - Reactive arthritis - Psoriatic arthritis - Arthritis with IBD - Undifferentiated SpA

Answer 165

Inflammatory back pain: 4/5 parameters fulfilled: - Age at onset < 40 years - Insidious onset - Improvement with exercise - No improvement with rest - Pain at night (with improvement upon getting up) In patients with >= 3 months back pain (w/ or w/o peripheral manifestations), onset < 45: - Sacroillitis on imaging + 1+ SpA feature - HLA-B27 + 2+ SpA features In patients with peripheral manifestations ONLY: - Arthritis, enthesitis (swelling at insertion of tendon into bone- commonly mistaken for achille's tendon tear) or dactiylitis (swollen toes) plus SpA features Seen in 16 common sites of joints

Answer 166

- Uveitis: photophobia in one eye - Aortic involvement - Pericarditis - Pulmonary fibrosis - Amyloidosis

Answer 167

1. Joint space inflammation 2. Erosive damage and repair 3. NEW BONE formation (versus RA)

Answer 168

Class II MHC (interaction between cells and environment) - Seen in 90% of Caucasian Ankylosing spondylitis patients - ONLY 1-2% HLA-B27 patients develop AS - Male to female 4:1 + women have milder disease (underdiagnosed) - Family history: 10-20% of patients with HLA-B27 will develop AS Strong association with GI inflammation - Reactive arthritis following shigella, salmonella, campylobacter - HLA-B27-positive patients with IBD have higher risk of developing reactive arthritis

Answer 169

MRI: - Lumbar spine - PA of pelvis Spinal mobility: chest expansion Schober test: spine should stretch by ~ 10 cm when bending forward

Answer 170

Acute inflammatory arthritis 1-4 weeks after infection - Asymmetric oligoarthritis - 75% Caucasian, 50% AA with reactive arthritis= HLA-B27+ - Triggered by: shigella, salmonella, yersinia, campylobacter, chlamydia, ureaplasma, HIV Seronegative asymmetric arthritis following: - Urethritis, cervicitis, infectious diarrhea Associated features: - Inflammatory eye disease, balanitis, oral ulceration, keratoderma, enthesopathy, sacroiliitis

Answer 171

Polygenic autoimmune disease characterized by: - Arthritis - Enthesitis - Spondylitis M=F Psoriasis in 2-3% population; - PsA in 6-48% of psoriasis patients depending on case series (probably ~25%) Risk factor= obesity; severity of psoraisis (not predictive of severity of arthritis; predictive of occurence) Subsets: 1. Asymmetric oligoarthritis (dactylitis)= sausage fingers 2. DIP arthritis 3. Rheumatoid arthritis-like polyarthritis 4. Psoriatic spondylitis 5. Arthritis mutilans 6. HIV associated psoriatic arthritis * * (50% of patients with axial scoriatic arthritis will be HLA-B27 positive,not in peripheral involvement)

Answer 172

IBD-associated Inflammatory arthritis (Crohn or UC) - NO association between HLA-B27 and peripheral arthritis - 50% association with HLA-B27 in axial involvement M=F, seen in younger patients with no age preference Peripheral joint enteropathic arthritis (5-20% cases): 1. Onset coincides with IBD symptons (abdominal pain, diarrhea) in 80% of cases but may also precede or follow the intestinal disease. 2. Attacks are typically acute, episodic, recurrent and parallel bowel disease activity. 3. Monoarthritis or asymmetric oligoarthritis (frequently migratory) involves the knee. Sausage fingers 4. The arthritis of IBD is rarely destructive unlike rheumatoid arthritis Spondylitis and Sacroiliitis: - Occur in up to 7% of Crohn’s and 25% of ulcerative colitis patients and are often asymptomatic. * Most often found in patients who are HLA-B27 positive. * Radiographic findings resemble those seen in AS. * Symptoms do not usually parallel activity of bowel disease.

Answer 173

Education, exercise, activity Peripheral disease: NSAIDs Sulfasalazine, local corticosteroids TNF blockers Axial disease: NSAIDs TNF blockers Hard to tell what the progression of disease will be - Monitor with MRI - Conservative use of TNF-alpha inhibitors - Systemic illness:

Answer 174

Large Vessel Vasculitis Used to be called temporal arteritis -- but it can involve more than just the temporal artery - Primarily affects the cranial branches of the arteries originating from the aortic arch - May affect the aorta - Most common primary form of vasculitis - Seen primarily in Caucasians of N. European descent (not in AA), F > M, increases with age Clinical presentation: - Severe unilateral headache with scalp tenderness - Jaw claudication and constitutional symptoms (fatigue, anorexia, weight loss) - Impaired blood flow to affected area causes symptoms: Vertebral (stroke), retinal (blindness) - Vision loss is most feared symptom, usually irreversible (anterior ischemic optic neuritis or retinal artery occlusion) Evaluation: - Physical exam: normal or show decreased pulse, thickened nodular artery - NO LAB testing: high ESR may be found - Biopsy can be helpful, not sensitive: biopsy every 1-2 cm to rule out "skip lesions"; biopsy both sides - Looking for granulomas around large vessels - No radiologic technique as specific as biopsy Treatment: - High dose steroids given severity of manifestations such as blindness

Answer 175

Patients report pain, stiffness in muscles of neck, shoulder, pelvic girdle - Associated with signs of systemic inflammation such as elevated ESR, CRP * * Dramatically Responsive to low dose prednisone (vs arthritis, which is mildly responsive) 40-60% patients with GCA have PMR symptoms - 15% of PMR patients will develop GCA; can be first symptom of GCA * * Low dose prednisone will not control GCA

Answer 176

Large vessel vasculitis VERY uncommon Primarily affects young Asian women < 40 years old - Affects large vessels: aorta, coronary, pulmonary arterties "Pulseless disease" Systemic signs and neurologic /cardiac symptoms - May have claudication of extremities Diagnosis: made with imaging but physical exam may show bruit - Imaging of vessels: any evidence of claudication Treatment: Steroids

Answer 177

Slight male predominence, broad age range - Constitutional symptoms - Strongly associated with Hep B infection Symptoms depend on organ affected by commonly affects GI tract: may also see: - HTN, neuropathy, testicular pain, cutaneous disease - Spares lung and glomeruli (can involve renal artery with aneurysms) Mononeuritis multiplex= Blood vessels that supply nerves attacked--> nerve death--> wrist/foot drop (most common cause of foot/wrist drop is diabetes) Evaluation: - No specific diagnostic tests - May see elevated inflammatory markers - Mesenteric/renal angiography- aneurysms, irregular constrictions - NOT ANCA-associated vasculitis Treatment: Immunosuppression required due to 2-5 year mortality - Degree of treatment guided by disease severity

Answer 178

Acute, self-limiting illness affecting young children, infants (85% < 5 years) - More common in Japan Symptoms: - Fever, congestions, conjunctival infection, oral cavity dryness/redness with blistering, lymph node swelling, rash on palms and soles ** May have later complications from cardiac disease (coronary arteries) Pathology: PAN-like vasculitis with necrosis and inflammation affecting the entire thickness of the vessel wall but with less prominent fibrinoid necrosis. Pathologic changes outside the cardiovascular system are rarely significant! ** Treated with intravenous immunoglobulin (IVIG) early (less than 10 days) decreases aneurysm formation by up to five-fold

Answer 179

ANCA= anti-neutrophil cytoplasmic antibody - C-ANCA: cytoplasmic antigens (PR3)= ELISA - P-ANCA: perinuclear antigens (MPO, many other antigens- less specific) 3 types; overlap in clinical features: 1. Wegener's granulomatosis= granulomatosis with polyangiitis (GPA) - C-ANCA or PR3 (proteinase 3) in 80-90% patients 2. Microscopic polyangiitis (MPA) - P-ANCA or MPO in 70% patients - Like GPA with no granulomas 3. Churg-Strauss= eosinophillic granulomatosis with polyangiitis (EGPA) - P-ANCA or MPO in ~50% patients Diseases treated similarly: immuno-suppressants chosen based on degree of organ involvement

Answer 180

M=F, peak in middle age - Patients usually have constitutional symptoms - Limited form: only involves upper respiratory tract and/or lower respiratory tract - Upper respiratory symptoms: chronic sinusitis, epistaxis, "infections" - Can see nasal perforations, "saddle nose" deformity Lower respiriatory symptoms: range from pulmonary infiltrates to alveolar hemorrhage - Cavitary nodules - Glomerulonephritis Likely to see increased inflammatory markers: ESR, CRP, ANCA - C-ANCA or PR3 in 80-90% patients Treatment: immunosupression

Answer 181

M=F, mean age= 40 - Majority of patients have asthma, atopy, allergy (ex: asthma that patient can't control with meds) - Can affect MULTIPLE organ systems (not just lung) - Symptoms depend on affected organ, can also include recalcitrant asthma Found with eosinophilia: - Biopsy shows eosinophilic inflammation, necrotizing vasculitis - Associated with P-ANCA, MPO

Answer 182

Ig precipitate in cold: 1. Type 1= monclonal antibody (IgG) 2. Type 2= Polyclonal IgG and monoclonal IgM RF - Often due to Hep C (treat Hep C, cure vasculitis), HIV 3. Type 3= polyclonal immunoglobulins Thought to induce disease through immune complex activation, deposition in vessels Clinical features: - Related to organ involvement - May see digital ulceration/cyanosis, Raynaud's phenomenon - Neuropathy, renal failure, rash

Answer 183

AKA Henoch-Schonlein purpura - Primarily affects children ~ 5 years - Most commonly diagnosed vasculitis in children - Common Upper respiratory tract infection followed by purpuric rash, arthralgias, abdominal pain - May also have glomerulonephritis Treatment: supportive (self-limiting in children)

Answer 184

Patients have urticarial lesions that lasts > 24 hours and SCAR - May also have arthritis, arthralgias, glomerulonephritis, uveitis, episcleritis, pulmonary involvement, abdominal pain Labs: - Low complements with low C1q level, anti-C1q antibodies May be from primary autoimmune disease- associated with other etiologies

Answer 185

Severe aphthous ulcers, genital ulcers, skin lesions, ocular involvement, all size blood vessels - More common in Middle Eastern male patients Pathergy: pustule forms where IV inserted into arm (unique to Behcet's)

Answer 186

Inflammatory disorder affecting eyes and ears, no direct test

Answer 187

Characterized by immune complex deposition in arterioles, venules, capillaries Systemic or primarily cutaneous: palpable purpura, maculopapular rash Biopsy: cutaneous leukocytoclastic angiitis- not confirmatory for autoimmune disease Therapy: remove inciting agent, immuno-suppression

Answer 188

Affects small and medium blood vessels in brain parenchyma, spinal cord, leptomeninges--> CNS dysfunction Male predominant, may occur at any age Rare disorder, poorly defined characteristics, incredibly difficult to diagnose - Can have normal CSR - See abnormal MRI/MRA (most likely due to HTN, other causes) - Need brain biopsy to confirm: should see vasculitis Treatment: high dose steroids, immune suppression

Answer 189

Inflammation of just the aorta - Numerous condition can cause it: Giant cell, Takayasu's, peri-aortitis (majority) - May be associated with retroperitoneal fibrosis - May see "soft rind" around aorta Treatment: immunosuppression

Answer 190

Not seen often following improved treatments for RA

Answer 191

See vascular and pulmonary involvement

Answer 192

Cocaine cut with antifungal powders causing immune response--> formation of C-ANCA and P-ANCA antibodies - Can lead to vasculitis, necrosis of nose, ears

Answer 193

Type I – Red, Slow Twitch, Oxidative - Antigravity muscles, sustained contraction - Red= Increased myoglobin, increased oxidative enzymes, more mitochondria - Conditioning increases mitochondria Type II- White, Fast Twitch, Glycolytic, - Increased glycogen, decreased myoglobin, - Hypertrophied with “aerobic exercise” - Hypertrophied with anabolic steroids - Atrophy with disuse Atrophy with corticosteroids

Answer 194

- X-linked – most common non-inflammatory myopathy of children - Particularly affects pelvic and shoulder girdles - Women are carriers, however 30% of cases are spontaneous. (Dystrophin gene is HUGE) - Mutation of dystrophin localized to Xp21 - Dystrophin links the cytoskeleton of the muscle cell to the sarcolemmal membrane. - DMD= complete or almost complete loss of dystrophin due to deletions of the gene. Path: - Dystrophin deficient fibers display osmotic fragility and undergo spontaneous necrosis. - Diagnosis: Immunohistochemical staining for dystrophin Western Blotting, PCR Disease characteristics: - necrosis of muscle fibers and regeneration - Regeneration is insufficient to keep pace and there is progressive loss of fibers and fibroadipose replacement. * Becker’s muscular dystrophy: dystrophin protein present but it is usually truncated. As a result, the disease is milder. Clinical DMD: - Weakness evident by age 3 or 4 - Pseudohypertrophy of the calf muscles - Wheelchair bound by age 10 years - Bedridden by 15 years - Death due to respiratory insufficiency and/or cardiac arrhythmias - brain is also affected (mild mental retardation)

Answer 195

Patients with LGMD show similar clinical features- weakness of the pelvic and shoulder girdles. - Onset may be in childhood or adulthood with variable muscle weakness. - Patients may have difficulty walking, running or rising from a sitting position. - Cardiac involvement is common. Histology: - Variants show unusual features including inflammation (LGMD2B, Miyoshi myopathy), rimmed vacuoles (LGMD1A) similar to those seen in inclusion body myositis Proper diagnosis requires: - detailed clinical history - battery of immunohistochemical, immunoblotting and genetic tests. - LGMD (2C through 2F) are also known as the sarcoglycanopathies.

Answer 196

Characterized by hypotonia, weakness and contractures (floppy kid) - Some variants associated with leukoencephalopathy, brain malformations and eye involvement. Path: resemble other muscular dystrophies, with variable fibrosis and fatty infiltration of the muscle. Some may also cause limb-girdle dystrophies, with different manifestations

Answer 197

Most common form of adult muscular dystrophy - Characterized by Myotonia (difficulty in relaxation) and progressive muscle weakness Two forms with autosomal dominant inheritance: 1. DM1= CTG trinucleotide repeat syndrome - Repeats in the DM protein kinase (DMPK) gene (Serine-threonine protein kinase) - Normal - 30 copies of the CTG repeat - Affected > 50 copies - Congenital forms in children of affected DM1 mothers - slowly progressive muscle weakness and stiffness are seen, principally in the distal limbs - Facial and neck weakness as well as ptosis 2. DM2= CCTG repeats in the first intron of the ZNF9 gene - Zinc Finger Protein (binds RNA) - Proximal weakness more common than in DM1 Extra skeletal muscular manifestations: - Cataracts, testicular atrophy, personality deterioration. - Smooth muscle disorders of the GI tract and uterus. - Cardiac arrhythmias ** Congenital myotonic dystrophy is seen in children of affected mothers.

Answer 198

``` Type I fiber atrophy (peculiar) Type II fiber hypertrophy Internal nuclei Ring fibers Mild necrosis and regeneration ```

Answer 199

Congenital Hypotonia - Decreased deep tendon reflexes, decreased muscle bulk, delayed motor milestones Changes usually limited to Type I fibers - No active muscle fiber necrosis and relatively mild increases (if any) of serum creatine kinase

Answer 200

Type of congenital myopathy: Autosomal Dominant Ryanodine receptor mutation - Calcium-release channel of sarcoplasmic reticulum. * May be associated with malignant hyperthermia. Muscle biopsy: - Type I fiber predominance with a central pale zone on oxidative stains (NADPH-Tr) - Ultrastructure shows loss of membranous organelles in the center of the fiber

Answer 201

Type of congenital myopathy: Previously synonymous with Myotubular Myopathy - Now considered two separate entities Central Nuclear Myopathy - Heterogeneous group characterized by the presence of centrally placed nuclei. 1. Recessive form 2. Autosomal dominant, adolescent onset - Clinically resembles limb-girdle muscular dystrophy forms Fibers resemble the myotubular stage in the embryogenesis of skeletal muscle - Dynamin 2 - gene involved in membrane trafficking, centrosome and actin assembly.

Answer 202

X-linked Myotubularin mutation - Phosphatase involved in Phosphatidyl Inositol signaling cascades Features: - Marked neonatal hypotonia - Respiratory failure at birth Path: - Centrally placed nuclei in both fiber types

Answer 203

Acquired disorders characterized by nonsuppurative inflammation with muscle fiber necrosis and elevated serum muscle enzymes - Insidious symmetrical proximal weakness except in inclusion body myositis where distal muscle weakness may be more prominent Thought to have an autoimmune origin- Association with other autoimmune and connective tissue disease: - Detection of autoantibodies - Response to immunosuppression (not inclusion body myositis)

Answer 204

Afflicts children and adults - Characteristic rash affecting the upper eyelids, face, and trunk - Increased association with an underlying malignancy (usually carcinoma) in males - Polymyositis and inclusion body myositis have a much reduced risk of underlying malignancy compared to dermatomyositis in adults. Pathogenesis: - Immune complex formation with IgG, IgM and complement including C5-9 membrane attack complexes in the walls of blood vessels - NOT direct attack on muscle; also affects dermis as vascular attack occurs here too Histology: - Microangiopathy with loss of capillaries, - **perifascicular atrophy** - Perivascular infiltrates of B and T cells, predominance of CD4+ T cells - Muscle infarcts - Skin rash also related to the microangiopathy

Answer 205

Inflammation focused on the muscle fibers themselves: - No microangiopathy as in dermatomyositis - Perifascicular atrophy absent - CD8+ T cell mediated cell injury - Frequent association between anti-Jo-1 (recognizes a histidyl-tRNA synthetase) as well as interstitial lung disease, Raynaud phenomenon, and nonerosive arthritis

Answer 206

Inflammatory features similar to polymyositis, but seen in 60+ years Path: - Rimmed vacuoles (best seen on modified Gomori Trichrome Stain) - Increase in ragged red fibers - Congo Red positive amyloid (Texas red optics) material including: Beta Amyloid, phosphorylated tau, alpha synuclein, ubiquitin, presenilins, parkin, etc. - Intravacuolar and intranuclear filamentous inclusions (EM) Treatment: - IVIG - Non responsive to immunosuppression (lymphocytes respond to muscle damage- don't cause it!)

Answer 207

Heterogeneous group of muscle diseases characterized by the formation of rod like structures - Autosomal dominant and recessive forms Path: Nemaline structures are electron dense and resemble Z-band material

Answer 208

AKA: Acid Maltase Deficiency, alpha 1,4 Glucosidase Deficiency, Pompe Disease - Various mutations Pathogenesis: - Acid Maltase is a lysosomal enzyme responsible for glycogen breakdown. - Deficiency results in lysosomal storage of glycogen (membrane bound) Clinical: - More severe the earlier the age of onset - In the neonatal form, there is macroglossia, cardiac, liver, and skeletal muscle storage. CNS also affected. Severe hypotonia - Later onset and adult forms, clinical expression limited to muscle, progressive muscle weakness.

Answer 209

AKA: McArdle Disease, Myophosphorylase Deficiency - Usually not progressive or debilitating Myophosphorylase is skeletal muscle specific - Deficiency results in an inability to cleave glycogen and release glucose for energy utilization during physical exertion Clinical: - Muscle cramping - Avoid strenuous exercise otherwise muscle necrosis, myoglobinuria and renal failure Diagnosis: - Absence of myophosphorylase, - PAS positive storage of non-membrane bound glycogen

Answer 210

Phosphofructokinase Deficiency - Less common than McArdles but similar syndrome since it interferes with glucose utilization - Slight anemia and hemolysis because of shared subunits of the enzyme in erythrocytes and muscle

Answer 211

Clinical: Exercise intolerance Path: Excess accumulation of neutral lipids (not CPT) Disorders of : - Deficient transport of fatty acids into mitochondria (carnitine deficiency syndromes and CPT deficiency) - Defects in enzymes of Beta oxidation pathway - Abnormalities of respiratory chain enzymes - Defects in triglyceride metabolism

Answer 212

Carnitine synthesized in the liver - Required for transport of LCFAs into mitochondria - Autosomal recessive Clinical: - Progressive muscle weakness and atrophy - Signs of denervation and peripheral neuropathy - Massive accumulation of lipid in muscle Treatment: Oral carnitine may help

Answer 213

Path: Inability to metabolize LCFAs due to inability to transport them into the mitochondria Clinical: - Prolonged exercise results in muscular pain, myoglobinuria - Prolonged fasting can do the same Histo: No light microscopic changes

Answer 214

Maternal inheritance for mitochondrial gene encoded proteins and tRNAs. - Nuclear-encoded mitochondrial proteins are autosomally inherited - Disease expression related to proportion of mutant mitochondria Energy hungry organs especially CNS and muscle (cardiac and skeletal) are affected most: - CNS= death of neurons Path: - Accumulation of mitochondria (SDH) - Ragged Red fibers (also seen in inclusion body myositis) - Lipid and glycogen accumulation due to improper metabolism - Atrophy of muscle fibers - COX deficiency * Ultrastructural abnormalities of mitochondria may be seen but are not present in all cases.

Answer 215

1. Kearnes-Sayre syndrome (KSS): - progressive ophthalmoplegia, retinal pigmentary degeneration, cardiac arrhythmias - large deletions of mtDNA 2. Chronic Progressive External Opthalmoplegia - Similar to KSS (only really seen in eyes): genetically autosomal dominant and recessive inheritance via nDNA - polymerase gamma (deletions), helicase, ANT1 (adenine nucleotide translocator-1) 3. MELAS-mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes - mutation in leucine tRNA mitochondrial-encoded gene 4. MERRF-myoclonic epilepsy and ragged red fibers. - mutation in the lysine tRNA mitochondrial-encoded gene

Answer 216

Trichinella spiralis: - Acquired from ingestion of undercooked meat from infected animals (mostly pork) - Encysted larva develop into adult worms within intestine. - Female worms release larvae that penetrate gut and encyst in skeletal muscle Clinical: - often asymptomatic - pain, tenderness, eosinphilia, periorbital edema - infection of brain or myocardium may be fatal

Answer 217

Risk Factors: - Secondary to metabolic myopathies - Crush injuries - May complicate influenza - Heat stroke - Malignant hyperthermia - Alcoholism - Sepsis Other causes: - Noninflammatory destruction of fibers with phagocytosis - Myoglobinuria and renal failure - HMG CoA reductase inhibitors (Cholesterol lowering drugs such as Lipitor).

Answer 218

Caused by: - Steroids - Chloroquine - Colchicine - Omeprazole - Statins= HMGCoA reductase inhibitors

Answer 219

Also known as Acute Quadriplegic Myopathy, or Myosin Heavy Chain Depletion Syndrome: - Classically results from the use of high-dose steroids and neuromuscular blocking agents. - Profound loss of myosin (thick filaments) with preservation of other sarcomeric structure. - Discontinuation of corticosteroids often results in reappearance of myosin filaments and recovery - Cause unknown

Answer 220

Degeneration of anterior horn cells - Second most common, lethal, autosomal recessive disorder after cystic fibrosis 1. Type I (Werdnig-Hoffman Disease, Infantile Spinal Muscular Atrophy): - Progressive and severe weakness in early infancy, death within 1-2 years. - Histology: atrophy of type I and II fibers with clusters of surviving hypertrophied type I fibers. 2. Type II Intermediate 3. Type III Kugelberg-Welander Disease, Juvenile Spinal Muscular Atrophy: - Later onset, not necessarily progressive - Fiber type grouping - Degenerating and regenerating fibers

Answer 221

- Weakness with repetitive motion; waxes and wanes - 10% overall mortality associated with respiratory insufficiency due to muscle weakness - Autoimmune attack on Ach receptors on motor endplates results in decreased numbers of receptors Cause: - 40% have thymomas - 75% of remaining patients have thymic hyperplasia Light microscopy: - Sparse lymphocytic infiltration - Type II fiber atrophy Ultrastructure: - Decreased folds at neuromuscular junction Treatment: - Thymectomy, immunosuppression, Ach-esterase inhibitors, plasmaphoresis

Answer 222

Paraneoplastic disorder characterized by: - muscle weakness, wasting and fatigue of the proximal limbs and trunk Usually associated with small cell CA of the lung but may be associated with other malignancies or may occur in isolation. IgG against voltage-sensitive calcium channels that are expressed in motor nerve terminals and in the cells of lung cancer - The calcium channels are necessary for release of Ach

Answer 223

- Incidence of 1.8 to 35 cases per 100,000/ year in general population - Prevalence fluctauates from 250000 to 1.5 million cases of lupus. - Women>Men – 9:1 ratio - African Americans>Hispanics>Whites - Usual onset between 15-45 years (60% cases)

Answer 224

``` Etiology is unknown • SLE is an autoimmune disease • Genetic factors – HLA association (HLA DR2/HLA DR3) • Environment factors – Sunlight, drugs, chemicals, foods – Bacterial or viral infections – More associated with flares and exacerbations • Hormonal factors – Increased estrogen and prolactin levels - Flares during pregnancy (vs RA) ``` Immune changes: - Abnormal complement components (C1q, C4, etc ) - Fc Receptor abnormalities - -> delay in clearing dying (apoptotic) cells, exposing more autoantigens.

Answer 225

Protean, may mimic Infectious Mononucleosis, lymphoma, etc - Criteria derived to establish/rule out diagnosis (patients might not fulfill criteria initially, but most will manifest over time): 1. Malar rash: Fixed erythema, flat or raised, sparing the nasolabial folds 2. Discoid rash : Raised patches, adherent keratotic scaling, follicular plugging; older lesions may cause scarring 3. Photosensitivity: skin rash from sunlight; feel worse after sun exposure 4. Oral ulcers: usually painless 5. Arthritis: nonerosive, inflammatory in 2+ peripheral joints 6. Serositis: pleuritis, pericarditis 7. Renal disorder: persistent proteinuria, cellular casts 8. Neurologic disorder: seizures, psychosis 9. Hematologic disorder: hemolytic anemia, leukopenia (< 4000/mm3), lymphopenia (< 1500/mm3) or thrombocytopenia (< 100,000/mm3) 10. Immunologic disorder: antibodies to dsDNA or SM or positive antiphospholipid antibodies (IgG or IgM, lupus anticoagulant, false-positive serologic test for syphillis- may see antibody to treponema phospholipids) 11. Antinuclear antibody positive

Answer 226

1. Arthritis (55%) 2. Skin involvement (25%) 3. Nephritis (5%) 4. Fever (5%) 5. Other (15%)

Answer 227

Joints 90%: - Arthritis and/or artharlgias are the most common presenting manifestation of SLE - Most cases: Symmetrical. - Unlike RA, is usually non-erosive ( at xrays) w/ subluxations, initially reversible. - Involve periarticular surfaces. - Increase frequency of tendon rupture. - Fibromyalgia can overlap joint sx. Skin - Rashes 70%: butterfly rash, interarticular dermatitis, palpable purpura - Discoid Lesions 30%: erythematous, hyperpigmented; flattened; scarred central areas with thin/fragile epidermis; follicular plugging * * Discoid lupus can become systemic lupus - Alopecia: diffuse 40% Pleuropericardium 60% - Serositis: pleuritic pain more frequent than effusions - Fluid exudative with normal glucose Pulmonary manifestations: - Pneumonitis - Pulmonary hemorrhage (small capillary leak) - PAH - Shrinking lung syndrome (diaphragm, respiratory muscles) Cardiac manifestations: - Most common cause of mortality in SLE is CAD - Endocarditis in 15-60% (asymptomatic)= Libman-Sacks endocarditis - Myocarditis in 9%: mild, seen as diastolic dysfunction - Clots in placental tissue--> miscarriages Kidney 50% Raynaud’s 20% Mucous Membranes 15% CNS (Seizures/Psychosis) 15%

Answer 228

Lupus nephritis= diffuse proliferative nephritis Membranous Lupus nephropathy Labs: Anti-DNA Antibody deposition, low complement Pathophys: activation will produce inflammation, occlusion and disruption of glomeruli that translate in: - Protein urinary excretion (Nephrotic Sd) - Hematuria (Nephritic Sd) - Increase on Creatinine levels - Renal Failure Class I: Normal glomeruli a) Nil by all techniques b) Normal by light but deposits on EM or IF Class II: Mesangial glomerulonephritis: mesangial cells affected Class III: Focal glomerulonephritis: endothelial cells affected Class IV: Diffuse glomerulonephritis: endothelial cells affected Class V: Diffuse membranous glomerulonephritis: epithelial cells affected Class VI: Advanced sclerosing glomerulonephritis

Answer 229

Discoid lupus: - Discoid lesions without syetemic disease - Can be unaccompanied by ANA or other autoantibodies. - 10% of patients with discoid lupus will develop the systemic illness. Drug induced lupus: - Procainamide - Hydralazine - induce the production of antinuclear antibodies, especially anti‑histone antibodies, and occasionally a SLE‑like illness. Drug- induced lupus characterized by: - fever, - hematological abnormalities such as an autoimmune hemolytic anemia or autoimmune thrombocytopenia, or serositis. - Skin, renal and neurologic manifestations are uncommon. Neonatal lupus/congenital lupus: - Produced by transplacental acquisition of autoantibodies, specifically anti‑Ro (SS‑A), - Produce in the neonate a transient photosensitive rash, congenital complete heart block, thrombocytopenia or rarely hepatobiliary dysfunction - Syndrome recedes 9 months after delivery - Screen mothers for ANA to prevent heart-block or other deadly problems in infant

Answer 230

Anti‑double stranded DNA (renal findings) Anti‑RNP, anti‑Smith, Anti‑ SSA (Ro), anti‑ SSB (La) Anticardiolipin, Glycoprotein, VDRL ( APS) Complements: C3, C4, CH50 Other testing: CBC, CMP, UA, CxR Hematological findings of SLE: - Anemia - Thrombocytopenia - Leukocytopenia - Lymphopenia

Answer 231

Chronic, autoimmune inflammatory disorder of exocrine (moisture producing) glands. - This produces a diminished lacrimal and salivary secretion (“sicca syndrome”) in association with autoantibody production. Epidemiology: - More frequent in middle aged patients (40-50’s). - More frequent in Caucasian Population. - 9:1 ratio of women:men. - Estimated prevalence 2-3 million people in the US. ( but varies between 0.3 -3%) - 2nd most common autoimmune rheumatic disease after rheumatoid arthritis. Primary Sjogren's: development of dry eyes, dry mouth in previously healthy person (no known connective tissue disease) Secondary Sjogren's: Associated with other autoimmune rheumatic disease- classically RA. Also seen with SLE, Systemic sclerosis - See Polymyositis, polyarteritis nodosa, relapsing polychondritis, primary biliary sclerosis

Answer 232

In most patients- slow and benign course. - Initial manifestations can be non-specific and usually many years elapse from the initial symptoms to the full-blown development of the syndrome. - Dry eyes and dry mouth are the presenting or initial manifestation in approximately 85% of cases - The classic triad of symptoms is dry eyes (keratoconjunctivitis sicca), dry mouth (xerostomia) and arthritis

Answer 233

Chronic inflammation of lacrimal glands: - produce decrease in tear production - Diminished tear production leads to the destruction of both corneal and conjunctival epithelium and a constellation of clinical findings termed keratoconjunctivitis sicca (KCS). Physical signs: - Dilation of the conjunctival vessels, pericorneal injection, (red eye) - Irregularity of the corneal image and lacrimal gland enlargement. - The patient usually complains of a burning, sandy or scratchy sensation under the lids, itchiness, redness and photosensitivity. - Failure to treat dry eyes may result in complications such as corneal ulcers or melting, corneal perforation, loss of vision, bacterial conjunctivitis or blepharitis (inflammation of the eyelids). Diagnostic questions: 1. Symptoms of dry eyes for at least 3 months? 2. A foreign body sensation in the eyes? 3. Use of artificial tears 3 or more times per day?

Answer 234

1. Dry mouth (xerostomia)--> decreased saliva - Difficulty swalling food, inability to speak, change in taste, burning sensation, increased in dental caries - Physical exam: dry, erythematous, sticky oral mucosa, dental caries, scanty/cloudy saliva, angular chelitis - Parotid, major salivary gland enlargement in 60% patients (episodic or chronic, unilateral--> bilateral) Complications: - accelerated caries, loss of dentition, poor fitting dentures, - oral candidiasis (yeast infection with Candida albicans), - sialolithiasis (salivary gland stones), - sialostenosis (salivary gland strictures), - bacterial sialadenitis (infection), - disturbed sleep (related to nocturnal fluid ingestion), - depression and weight loss (related to oral discomfort, dysphagia etc.). Diagnostic questions: 1. Symptoms of dry mouth for at least 3 months? 2. Recurrent or persistently swollen salivary glands? 3. Need for liquids to swallow dry foods?

Answer 235

More CD4 than CD8 - The subsequent local production of lymphokines, cytokines and antibodies is eventually followed by fibrosis (scarring) and fatty tissue replacement of normal glandular parenchyma. - Disruption of neural innervation may also affect glandular secretion and cause diminished function. - This process leads to permanent glandular destruction and irreversible dysfunction

Answer 236

3/4 standard criteria: 1. Objective documentation of dry eyes - Schirmer's test: measures tear production on strip of paper in eye duct (normal > 10mm/5 min) - Rose Bengal/ fluorescien corneal staining: ocular surface irregularity or damage due to dryness - Tear break film test: tear film stability between last blink and appearance of dark, non-fluorescent areas in tear film (normal > 10 seconds) 2. Objective documentation of dry mouth - Oral examination: diminished salivary pool, loss of glistening of tongue, mucous membranes, erythema, fissures on tongue - Sialometry: Measure salivary flow using Lashley cup; circular cup connected to plastic tube, collect parotid saliva (placed over Stensen's duct)- normal resting = 0.1 ml/min, after citric acid = 0.5-1.5 ml/min - Salivary scintigraphy: nuclear medicine test to measure isotope uptake into glands (saliva formation) plus stimulated salivary discharge - Sialography: inject contrast medium into salivary ducts followed by routine x-rays (MRI) 3. Demonstration of autoimmunity through blood tests - Positive ANA, Rheumatoid Factor (> 1:160) - Positive anti-SSA (Ro) or anti-SSB (La) 4. Confirmation of histologic involvement by salivary gland biopsy - Labial minor salivary gland biopsy on inner aspect of lip - Findings: focal lymphocytic sialadenitis= accumulation of 50+ mononuclear cells around salivary gland acini, ducts 1. Divide number of foci by glandular surface area= focus score 2. Focus score > 1/4 mm3= Sjogren's

Answer 237

Arthritis: - 50% experience arthritis in disease - May precede overt sicca manifestations - Arthralgias, morning stiffness, intermittent synovitis, chronic polyarthritis - Non-erosive changes in hands Skin: - Raynaud's Pulmonary: - Frequent, not important - Dry cough secondary to dryness of tracheobronchial mucosa (xerotrachea) or dyspnea due to airway obstruction - Recurrent broncho-pneumonia - Interstitial lung disease - **Lymphoma should be suspected when lung nodules/hilar or mediastinal lymphs visible on CXR CNS: peripheral, cranial neuropathy Kidneys: interstitial nephritis, renal tubular acidosis

Answer 238

``` Amyloidosis Chronic sialadenitis Diabetes mellitus Eosinophilia-myalgia syndrome Graft-versus-host disease Medication-related dryness ( anticholinergics, antidepresants, etc) Mouth breathing Multiple sclerosis Radiation injury Sarcoidosis Salivary diffuse infiltrative lymphocytosis syndrome (HIV related) Silicone breast implant disease Sjogren’s syndrome (1º or 2º) Type 5 hyperlipidemia IgG4 disease ```

Answer 239

``` Abnormal liver functions tests Antinuclear antibodies Anti-SS(Ro) or anti-SS(La) marker autoantibodies Elevated ESR** Elevated serum B2 microglobulin** Leukopenia Lymphopenia Normocytic normochromic anemia Polyclonal gammopathy Rheumatoid factor** ``` **= indicative of disease activity

Answer 240

``` Immunosuppression: -** Hydroxychloroquine - Azathioprine - Methotrexate - Rituximab - Corticosteroids - Cyclophosphamide - Cyclosporine All improve extra-glandular manifestations (fatigue, arthritis, interstitial pneumonitis, CNS involvment), but do not improve dry eyes/dry mouth - Can decrease disease progression ``` Sialogogues (stimulate saliva flow)/ Tear stimulants work best to relieve symptoms in patients with glandular functionality: 1. Pilocarpine (older drug): cholinergic agonist (M3 receptors)- can cause sweating, urinary frequency 2. Ceviniline: newer secretagogues