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MSK/Derm Flashcards

1
Q

[Osteogenesis]
1. Intramembranous ossification
A. Process
B. Bones formed from this process

  1. Endochondral ossification
A

1A. Intramembranous ossification - bone tissue laid down directly in embryonic connective tissue or mesenchyme

  • mesenchyme condenses within vascularized collagen matrix
  • mesenchymal stem cells differentiate into osteoblasts (via Sox9, Runx2)
  • osteoblasts secrete bone matrix –> woven bone
  • woven bone (immature) remodeled into lamellar

B. Forms membranous flat bones of the head (skull, midface, jaw) + clavicle

2A. Endochondral ossification - bone tissue replaces preexisting hyaline cartilage

  • mesenchymal condensation
  • chondrocytes differentiate –> Type 2 Collagen = cartilage
  • chondrocytes hypertrophy –> Type 10 collagen (in fetal cartilage)
  • primary ossification center forms with artery bringing pre-osteoblast cells; bone matrix formation –> Type 1 collagen (bone)

B. Bones of limbs and girdle

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2
Q

[Osteogenesis]

  1. Differentiate cortical vs trabecular bone
  2. Differentiate osteoblasts vs osteocytes vs osteoclasts
A

1A. Cortical (compact) bone - long bone shafts with concentric layers of mineralized collagen; outer periosteal and inner endosteal surface

  • functional unit is osteon
  • hard, strong, and stiff to support body

B. trabecular (cancellous, spongy) bone - axial skeleton and ends of long bones with interconnecting meshwork of rods and plates

  • functional unit is trabecula
  • highly vascular

2A. osteoblasts - on surfaces of bone matrix

  • synthesize bone matrix –> osteoid (type I collagen + GAGs + osteopontin), hydroxyapatite
  • regulate osteoclastogenesis (via RANKL and OPG)
  • communicate with osteocytes
  • derived from mesenchyme

B. osteocytes - 90% of adult bone cells, derived from osteoblasts
- communicate with osteoblasts - mechanical function to sense stress and stimulate anabolism

C. osteoclasts - secrete H+ to dissolve mineral of bone matrix (hydroxyapatite) and resorb bone

  • multi-nucleated; derived from hematopoietic progenitors (circulating monocytes)
  • require RANKL and M-CSF for maturation
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3
Q

[Osteogenesis]

  1. Camptomelic dysplasia
  2. Cleidocranial dysplasia
  3. Achondroplasia
A
  1. Camptomelic dysplasia - AD Sox9 mutation (regulates commitment to chondrogenic lineage)
    - short-limbed dwarfism and neonatal death
  2. Cleidocranial dysplasia - AD Runx2 mutation (regulates commitment to osteoblast lineage)–> cartilage skeleton but no bone; no clavicles
  3. Achondroplasia - AD gain of function mutation in fibroblast growth factor 3 receptor (FGFR3) at paternal allele–> inhibits chondrocyte growth and induces terminal differentiation of endochondral ossification
    - most common cause of short-limb dwarfism
    - normal head with frontal bossing, torso normal size
    - associated with advanced paternal age
    - full penetrance; majority are new gene mutations
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4
Q 
[Osteogenesis]
1. Osteogenesis imperfecta 
A. Cause
B. Type 1 vs Type 2
C. Clinical
A
  1. Osteogenesis imperfecta “brittle bone disease”
    A. Cause - Type 1 collagen mutations most commonly COLIA1 and COLIA2
    i. Qualitative - misfolding, problems forming triple helix
    ii. Quantitative - 􏰁↓ production of normal Type 1 collagen in bone, dentin, cornea

B. Type 1 vs Type 2
Type 1 - most common form; quantitative defect due to AD autosomal dominant mutations
Type 2 - due to qualitative defect; skeletal deformity with intrauterine fractures

C. Clinical

i. Type 1 can be confused with child abuse
- normal stature but multiple fractures with minimal trauma
- blue sclera (thin, can see choroidal vessels below)
- hearing loss (abnormal ossicles)
- tooth abnormalities, wear easily due to lack of dentin (dentinogenesis imperfecta)
ii. Type 2 - perinatal lethal

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5
Q 
[Osteogenesis]
2. Osteopetrosis
A. Cause 
B. Pathogenesis
C. Clinical 
D. Treatment
A
  1. Osteopetrosis “Marble bone disease”

A. Cause - genetic defects in RANKL, RANK, OPG, carbonic anhydrase 2 –> latter impairs ability to create acidic environment for resorption

B. Pathogenesis - failure of osteoclasts to resorb bone –> thickened, dense bone that is prone to fracture
- bone fills marrow space –> pancytopenia, extramedullary hematopoiesis

C. Clinical

  • bone-in-bone appearance on X-rays e.g. Ehrlenmeyer flask deformity of femur
  • bone fractures
  • cranial nerve impingement –> narrowed foramina –> palsies, vision and hearing impairment
  • Type II renal tubular acidosis (carbonic anhydrase mutation) –> loss of bicarb in urine

D. Treatment - bone marrow transplant is curative (osteoclasts are derived from monocytes)

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6
Q

[Bone tumors]
Describe including locations, histology, and clinical features
1. Metastases
2. Osteoma

A
  1. Metastases - most common malignant tumors involving bone; typically involve axial skeleton, femur, humerus (due to red marrow in these areas)
    “Permanently Relocated Tumors Like Bone”–>
    - Prostate osteoblastic
    - Renal
    - Thyroid/testes
    - Lung
    - Breast
  2. Osteoma - benign tumors
    A. Location - masses (exophytic lesions) attached to membranous bone surface –> facial bones, skull
    B. Histology made of mature lamellar bone (but no fibrous component)
    C. Clinical - solitary, slow-growing, clinically silent unless it obstructs and causes problems with breathing, vision, hearing
    - Gardner syndrome = FAP + soft tissue syndrome (multiple osteomas) + impacted teeth
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7
Q 
[Bone tumors]
Describe including locations, histology, and clinical features
3. Osteoid osteoma
4. Osteoblastoma
5. Osteosarcoma
A
  1. Osteoid osteoma - benign tumors <2 cm
    A. Location - occur <25 yo in cortex of the shafts of long bone –> femur
    B. Histology - woven bone rimmed by osteoblasts –> produce excess PGE2 –> pain
    C. Clinical - chronic aching, intense pain that is worse at night and highly responsive to oral salicylates (aspirin)
    - X-ray - central lucency surrounded by halo of radiodense reactive cortical bone
  2. Osteoblastoma - similar to osteoid osteoma in age (<20 yo) and histology but are larger, arise in vertebral spinal column, and unresponsive to salicylates
    - –
  3. Osteosarcoma - most common primary malignant bone tumor most common bone neoplasia = multiple myeloma
    - germline mutations - Rb and Li-Fraumeni (p53)
    - M»F

A. Location - long bones near growth plates (metaphysis) –> distal femur / proximal tibia (knee area), proximal humerus (shoulder area)
bimodal distribution:
i. Primary (75%) - 10-20 yo (due to rapid bone growth) –> metaphyses adjacent to growth plate of long bones
ii. Secondary (25%) - >65 yo with known risk factors (Paget’s, bone infarct, irradiation)

B. Histology - malignant spindle cells with mitotic figures making their own osteoid

C. Clinical - chronic pain - sometimes swelling, palpable mass (with pulsations)

  • decreased ROM
  • “sunburst” appearance and Codman triangle on X-Ray –> tumor destroying cortex and lifting periosteum
  • NOT common - fractures, systemic symptoms
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8
Q

[Bone tumors]
Describe including locations, histology, and clinical features
1. Ostechondroma
2. Multiple hereditary osteochondroma

A
  1. Ostechondroma aka exostosis
    A. Location - arise at metaphysis near growth plate of long bones, especially near the knee
    - males < 25 years old

B. Histology - solitary, cartilage-capped tumor attached by bony stalk to underlying skeleton
- cartilage cap looks like disorganized growth plate

C. Clinical - mostly asymptomatic, due to slow-growing mass

  • most common benign bone tumor
  • rarely transforms to osteochondroma
  • –
  1. Multiple hereditary osteochondroma
    A. Location - near the knee, multiple lesions that develop in childhood

B. Histology - same as osteochondroma
- chondrocyte differentiation disrupted –> abnormal cartilage growth

C. Clinical - bones may be bowed and shortened
- ↑ risk chondrosarcoma

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9
Q

[Bone tumors]
Describe including locations, histology, and clinical features
3. Enchondroma
4. Chondrosarcoma

A
  1. Enchondroma - benign neoplasm of hyaline cartilage
    A. Location - centrally located in medullary cavity of long bones esp metaphyses of short tubular bones of hands and feet

B. Histology - nodules of hyaline cartilage rimmed by narrow band of reactive bone

  • not infiltrative, no mitotic figures
  • well-defined, lucent with internal mineralization on X-ray *must exclude chondrosarcoma (look radiologically similar)

  1. Chondrosarcoma
    A. Location - mostly primary lesions, secondary is preexisting lesion (Paget, radiation)
    - axial skeleton - pelvis, axial skeleton (eg femur), and ribs
    - older age - 60+ yo

B. Histology - produces exclusively cartilage
- endosteal scalloping, calcified matrix on X-ray

C. Clinical - painful, progressively enlarging mass

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10
Q

[Bone tumors]
Describe including locations, histology, and clinical features
5. Ewing Sarcoma

A
  1. Ewing Sarcoma - primary malignant tumors of bone and soft tissue

A. Location - arises in medullary cavity (diaphysis) and invades cortex, periosteum, and soft tissue

  • diaphysis of long tubular bones chondrosarcoma, osteosarcoma occur along the joint
  • boys < 15 years old, whites > blacks
  • t(11;22) translocation

B. Histology - derived from neural crest and mesenchymal stem cells

  • anaplastic small blue cell malignant tumor
  • Homer-Wright rosettes (tumor cells arranged in circle about neuropil) –> indicates neural differentiation (seen in other tumors of children eg medulloblastoma, neuroblastoma)
  • X-ray shows lytic tumor extending into soft tissue
  • periosteal reaction –> layers of reactive bone deposited in “onion skin” fashion

C. Clinical - painful enlarging mass that is tender, warm, swollen

  • systemic findings - fever, anemia, ↑ ESR, anemia
  • extremely aggressive with early mets but responds to chemo (actinomycin D)
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11
Q

[Bone tumors]
Describe including locations, histology, and clinical features
6. Giant cell tumor

A
  1. Giant cell tumor = osteoclastoma

A. Location - arise in the knee at the epiphysis
- lytic lesion with soap bubble appearance on X-ray

B. Histology - neoplastic cells are osteoblasts –> make large amount of RANKL –> stimulates osteoclast proliferation and differentiation –> highly destructive resorption of bone matrix

C. Clinical - arthritis, pathologic fracture

  • locally aggressive benign tumor
  • 20-40 years old
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12
Q

[Bone tumors]

  1. Fibrous cortical defects
  2. Fibrous dysplasia
A
  1. Fibrous cortical defects - developmental defects in children; metaphysis of distal femur/proximal tibia (knee area)
    - asymptomatic, spontaneously remodeled to normal bone
    - storiform (whorls of spindled fibroblast-like cells) with scattered osteoclast-like giant cells
  2. Fibrous dysplasia - benign tumor –> localized development arrest - all components of bone present but do not mature (arise during skeletal growth and development)
    - intramedullary, well-circumscribed, trabeculae of woven bone that does not develop into solid lamellar bone
    - can be monostotic or polystotic (involve multiple bones),
    or part of McCune-Albright Syndrome - cafe au lait skin pigmentations, polyostotic fibrous dysplasia, and endocrine abnormalities, and precocious puberty
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13
Q 
[Review upper extremity lecture]
Upper extremity nerves - causes of injury and presentation
1. Axillary 
2. Musculocutaneous
3. Radial
A
  1. Axillary (C5-C6) –> innervates deltoid, sensation to skin overlying deltoid
    A. Causes - anterior shoulder dislocation, fracture of surgical neck of humerus
    B. Clinical - flattened deltoid, loss of sensation over deltoid
    - associated with posterior circumflex artery
  2. Musculocutaneous (C5-C7) –> innervates corachobrachialis, biceps, brachialis
    A. Causes - upper trunk compression
    B. Clinical - loss of forearm flexion and supination, loss of sensation over lateral forearm
  3. Radial (C5-T1) –> innervates posterior muscles of forearm (triceps, brachioradialis)
    A. Causes - compression of axilla (Sat night palsy, crutch injury); midshaft fracture of humerus, radial head subluxation (pulled elbow on child tearing annular ligament), dorsal wrist laceration eg handcuffs (only sensory loss)
    B. Clinical *depends on location of injury
    - loss of elbow extension
    - loss of wrist extension –> wrist drop
    - loss of thumb, finger extension
    - loss of sensation over posterior forearm and dorsal hand
    - associated with deep brachial artery
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14
Q 
[Review upper extremity lecture]
Upper extremity nerves - causes of injury and presentation
4. Median 
5. Recurrent branch of median nerve 
6. Ulnar
A
  1. Median (C5-T1)
    A. Causes - median nerve runs through antecubital fossa; supracondylar fracture of humerus (more commonly pediatric), carpal tunnel syndrome, wrist laceration, FOOSH (lunate dislocation, Colles’ fracture)
    B. Clinical
    - weak wrist flexion with ulnar deviation (adduction), loss of pronation
    - loss of thumb opposition –> atrophy of thenar eminence + “ape hand”
    - (elbow injury) loss of flexion of digits 2 and 3 –> “sign of benediction” on trying to make a fist
    - (wrist injury) loss of 1st and 2nd lumbricals –> “median claw” of digits 2 and 3 on resting
    - loss of sensation over lateral palm of hand
  2. Recurrent branch of median nerve
    A. Causes - superficial laceration of palm
    B. Clinical - ape hand, atrophy of thenar muscles (OAF), no loss of sensation
    *thenar eminence sensation is also spared in carpal tunnel syndrome (atrophy of LOAF muscles)
  3. Ulnar (C8-T1)
    A. Causes - ulnar nerve runs through cubital tunnel; dislocation of elbow with posterior dislocation of ulna, fracture of medial epicondyle (funny bone), fracture of hook of hamate (FOOSH)
    B. Clinical -
    - (proximal injury) loss of lumbricals 3 + 4 –> “ulnar claw” on digit extension / at rest; radial deviation on wrist flexion (abduction)
    - (elbow injury) weakness in wrist flexion / adduction
    - loss of finger abduction and adduction (interossei)
    - loss of thumb adduction, hypothenar atrophy
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15
Q 
[Review upper extremity lecture]
Brachial plexus lesions - innervations, causes, muscle deficit, and clinical condition 
1. Long thoracic nerve
2. Upper trunk
3. Lower trunk
A
  1. Long thoracic nerve (C5-C7) –> innervates serratus anterior muscle
    A. Causes - surgical (Axillary node dissection after mastectomy), stab wounds
    B. Clinical - winged scapula –> cannot abduct abduct arm above horizontal position
  2. Upper trunk (C5-C6)
    A. Causes - lateral traction on neck during delivery (infants), motorcycle fall (adults)
    B. Clinical - “waiter’s tip”
    - arm adducted / hangs by side (deltoid, supraspinatus - abduction)
    - arm medially rotated (infraspinatus - lateral rotation)
    - arm extended, forearm pronated (biceps - flexion, supination)
  3. Lower trunk (C8-T1)
    A. Causes - upward force on arm during delivery (infants), grabbing tree branch to break fall (adults)
    B. Clinical - loss of all intrinsic hand muscles (loss of median and ulnar nerve) –> “Klumpke palsy” –> total claw hand –> extension of MCP and flexion of PIP and DIPs
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16
Q 
[Review lower extremity lecture]
Innervations, causes, muscle deficits, clinical condition
1. Femoral nerve
2. Obturator nerve
3. Superior gluteal nerve 
4. Inferior gluteal nerve
A
  1. Femoral nerve (L2-L4)
    A. Innervations - muscles of anterior thigh
    - quads –> knee extension
    - iliopsoas, pectineus, sartorius –> hip flexion
    B. Causes - rare, pelvic fracture or spontaneous retroperitoneal hematoma
    C. Clinical
    - loss of sensation over anterior thigh and medial leg (L4 is over the knee)
    - loss of hip flexion and knee extension –> “quadriceps gait” where you put pressure on thigh to take next step (otherwise your knees buckle)
  2. Obturator nerve (L2-L4)
    A. Innervations - muscles of medial thigh
    - adductors (longus, brevis, magnus), gracilis, obturator externus –> hip/thigh adduction
    B. Causes - pelvic surgery
    C. Clinical - leads to medial thigh wasting and groin pain, loss of hip adduction
  3. Superior gluteal nerve (L4-S1)
    A. Innervations
    - gluteus medius and minimus –> hip abduction
    - tensor fascia latae –> hip flexor
    B. Causes - IM injection (should do superolateral quadrant to avoid injury)
    C. Clinical - leads to positive Trendelenberg sign - opposite side pelvic drop when standing on one foot bc gluteus medius and minimus cannot keep pelvis level
  4. Inferior gluteal nerve (L5-S2)
    A. Innervations - gluteus maximus –> hip extension
    B. Causes - iatrogenic, posterior hip dislocation (passive internal rotation)
    C. Clinical - leads to gluteus maximus gait –> lurch backwards on heel strike; difficulty rising from seated position, climbing stairs
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17
Q 
[Review lower extremity lecture]
Innervations, causes, muscle deficits, clinical condition 
1. Sciatic nerve
2. Common peroneal nerve
3. Tibial nerve
A
  1. Sciatic nerve (L4-S3) tibial + common peroneal nerve, which separate proximal to popliteal fossa
    A. Innervations - muscles of posterior thigh
    - hamstrings (Semitendinosus, semimembranosus, biceps femoris) –> knee flexion
    B. Causes - posterior hip dislocation (passive internal rotation), hip replacement surgery
    C. Clinical - weak knee flexion, knee hyper-extends while walking (polio gait)
    - leads to loss of ankle DTRs, loss of achilles reflex, wasting of calf muscles
  2. Common peroneal / fibular (L4-S2) *most common LE injury
    A. Innervations - anterolateral compartments of leg
    - lateral (superficial nerve) –> everts foot, sensory to dorsum of foot
    - anterior (deep nerve) –> dorsiflexes foot, extends toes *injured in anterior compartment syndrome
    B. Causes - fibular neck fracture, lateral blow to knee, leg cast, stirrups
    C. Clinical - “steppage gait” foot drop
    - loss of sensation to dorsum of foot
  3. Tibial (L4-S3)
    A. Innervations - posterior compartment of leg + muscles of foot
    - gastrocnemius, soleus (triceps surae / calf muscle) + plantaris –> plantarflex foot, inverts foot
    - flexor muscles of foot –> flex and abduct toes
    B. Causes - rare, baker cyst or knee trauma
    C. Clinical - foot is everted and dorsiflexed (can’t stand on tiptoes)
    - loss of sensation to sole of foot (plantar foot)
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18
Q 
[Review lower extremity lecture]
Knee injuries incl causes + tests / findings
1. ACL 
2. PCL
3. MCL
4. LCL
5. Unhappy triad
A
  1. ACL (attaches lateral femoral condyle to anterior tibia)
    A. Cause - deceleration, noncontact injury with “pop”
    B. Findings
    - anterior drawer test (90 angle) - tibia moves anteriorly
    - lachman (30 degrees)
  2. PCL (attaches medial femoral condyle to posterior tibia)
    A. Cause - fall onto / contact with flexed knee with “pop”
    B. Findings
    - posterior drawer + lachman tests - tibia moves posteriorly / femur slides forward
  3. MCL
    A. Cause - valgus lateral force (abduction)
    B. Findings - abnormal passive abduction
  4. LCL
    A. Cause - varus force (adduction)
    B. Findings - abnormal passive adduction
  5. Unhappy triad - common injury in contact sports
    A. Cause - lateral force applied to planted leg
    B. Findings - damages ACL, MCL, and meniscus
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19
Q

[Myopathies]
Inflammatory idiopathic myopathies including epi, cause, histology, and clinical presentation

  1. Dermatomyositis
A
  1. Dermatomyositis
    A. Epi - affects adults F>M, associated with ↑ risk carcinoma

B. Cause - autoantibodies anti-Jo1 and anti-Mi2, ANA (+) –> complement-mediated capillary injury, target blood vessels (which are in perimysium) –> lymphocytic invasion with CD4+ T cells in perimysium

C. Histology - perifascicular atrophy

  • ↑ CK (>10x normal) - detects muscle damage / inflammation
  • increased lactate dehydrogenase

D. Clinical
i. proximal, symmetric muscle weakness –> trouble climbing stairs, rising from seated position, raising arms; head drop, dysphagia

ii. cutaneous
- purple rash of upper eyelids (heliotrope rash)
- red papules on extensor surfaces (Gottron papules)
- sun-exposed, photosensitive rash

iii. systemic - interstitial lung disease, mechanic’s hands (cracking of finger pad skin)

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20
Q

[Myopathies]
Inflammatory idiopathic myopathies including epi, cause, histology, and clinical presentation

  1. Polymyositis
  2. Inclusion body myositis
A
  1. Polymyositis
    A. Epi - F>M, diagnosis of exclusion
    B. Cause - anti-Jo-1 Ab –> lymphocytic invasion with CD8+ T cells in endomysium; muscle fibers express MHC Class I
    C. Histology - necrosis of muscle fibers
    - ↑ CK (>10x normal)
    - increased lactate dehydrogenase
    D. Clinical - same as dermatomyositis (proximal symmetric muscle weakness, mechanic’s hands, interstitial lung disease) MINUS the cutaneous involvement
  2. Inclusion body myositis
    A. Epi - older men
    B. Cause - idiopathic, no autoAb
    C. Histology - CD8+ T cells in endomysium (like in polymyositis)
    - muscle fibers contain vacuoles and abnormal cytoplasmic inclusions that have proteins associated with neurodegenerative disease
    D. Clinical - asymmetric muscle weakness; starts in distal upper extremities (eg forearms), distal anterior compartment leg muscles, and quads
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21
Q

[Myopathies]
Muscular dystrophy including epi, cause, histology, and clinical presentation
1. Duchenne MD
2. Becker MD

A
  1. Duchenne muscular dystrophy
    A. Epi - presents in childhood (not infancy)

B. Cause - X-linked recessive mutations in dystrophin (provides mechanical support for muscle cells that interact with ECM) –> muscle fibers degenerate with loss of support
- Duchenne MD - deletion of dystrophin due to frameshift mutation

C. Histology - segmental myofiber degeneration and fatty replacement with adipose tissue
- ↑ CK (detects muscle inflammation / damage)

D. Clinical - weakness, proximal and lower, then distal and upper extremities

  • calf pseudohypertrophy (thick but mostly fat)
  • Gower’s sign - need to use upper extremities to get up off the floor
  • cardiac dysfunction (involves myocardium) - shorter life expectancy, death from cardiac or respiratory failure
  • –
  1. Becker
    A. Epi - same
    B. Cause - X-linked recessive, mutated dystrophin
    C. Histology - same
    D. Clinical - presents later and with milder symptoms
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22
Q

[Myopathies]
Muscular dystrophy including epi, cause, histology, and clinical presentation
3. Myotonic dystrophy

A
  1. Myotonic dystrophy
    A. Epi - onset in early adulthood

B. Cause - AD inherited trinucleotide repeat of CTG in 3’ untranslated region of DMPK gene –> creates 3’ hairpin loop –> sequesters RNA binding and splicing proteins from nearby genes –>

  • full mutation > 50 CTG repeats
  • both parents can transmit, but most severe form is inherited from mother

C. Histology -

D. Clinical

i. Mild - mild myotonia, cataracts
ii. Classic DM1 (50-1000 repeats) - adult-onset muscular dystrophy (muscle wasting and weakness) +
- myotonia (inability to relax voluntary muscle after vigorous effort)
- cataracts
- balding
- cardiac conduction defects (cardiomyopathy)
- insulin resistance –> DM2
iii. Severe - infantile hypotonia

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23
Q 
[Neuromuscular junction disorders]
Myasthenia gravis
1. Epi 
2. Pathophysiology
3. Clinical 
4. Triggers
5. Treatment
A

Myasthenia gravis
1. Epi - F>M, bimodal age peak, autoimmune

  1. Cause / Pathophysiology - Ab that target ACh nicotinic postsynaptic receptors –> compete with ACh for receptors –> bind, cross-link, and endocytose receptors –> damage postsynaptic muscle membrane
  2. Clinical - specific muscle weakness that worsens with repeated muscle use / stimulation –> worsens throughout the day; normal DTRs
    - first is extraocular muscle weakness –> diplopia, ptosis
    - then spreads from ocular –> facial –> bulbar –> truncal –> limb muscles
    - bulbar muscle weakness (with MuSK Ab) –> speech, swallowing problems
    - associated with thymic hyperplasia or thymoma (thymus = where T cells mature)
  3. Triggers - emotional stress, menstruation, viral infection, bright sunlight
  4. Treatment - pyridostigmine, neostigmine (Anticholinesterase inhibitor) –> more ACh to compete with the Abs –> symptom relief
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24
Q 
[Neuromuscular junction disorders]
Lambert-Eaton Myasthenic Syndrome
1. Epi 
2. Pathophysiology
3. Clinical 
4. Treatment
A

Lambert-Eaton Myasthenic Syndrome

  1. Epi - paraneoplastic - associated with small cell lung cancer (cancer expresses calcium channels) –> M>F, in smokers
    - or can be autoimmune (F>M, no correlation with smoking)
  2. Pathophysiology - Ab against voltage-gated Calcium channels on presynaptic motor nerve terminal –> inhibits Ca2+ influx –> diminished neurotransmitter release
  3. Clinical - proximal muscle weakness - for months to years –> decreased DTRs, difficulty climbing stairs, walking
    * muscle weakness improves with use (opposite of MG)
    - eyes are usually spared
    - autonomic sx - dry mouth, constipation, erectile dysfunction, dry eyes
  4. Treatment - search for small cell lung cancer
    - anticholinesterase agents do not improve symptoms
    - aminopyridines - block K+ channels –> allow depolarization to last longer –> more ACh released from terminal
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25
Q 
[Neuromuscular junction disorders]
Organophosphate poisoning 
1. Epi 
2. Pathophysiology
3. Clinical 
4. Treatment
A

Organophosphate poisoning
1. Epi - worldwide usage as insecticides

  1. Pathophys - bind to acetylcholinesterase –> prevents acetylcholine from being broken down
    - sarin gas has same MOA
3. Clinical - cholinergic excess --> DUMBELS
D-diarrhea
U-urination
M-miosis
B-bradycardia, bronchoconstriction
E-emesis
L-lacrimation 
S-salivation
  1. Treatment -
    - pralidoxime –> acute antidote; displace organophosphates to prevent aging (irreversible inhibition of acetylcholinesterase) and regenerate AChE
    - atropine - blocks ACh interaction with receptor
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26
Q 
[Osteoarthritis]
Osteoarthritis 
1. Epi / risk factors
2. Pathophysiology
3. Pathologic features
4. Clinical presentation
A

Osteoarthritis

  1. Epi - most common joint disease
    - risk factors - age, female, obesity (knee), joint trauma or microtrauma
    - commonly affects knees, hips, hands, spine
  2. Pathophys - damage to normal articular cartilage –> chondrocyte repair with defective cartilage –> abnormal joint loading –> cracking, fracturing of cartilage
    - histology - fibrillation of cartilage (small fractures)
  3. Pathologic features
    A. osteophytes (bone spurs)
    B. joint space narrowing due to increased subchondral bone (sclerosis)
    C. subchondral bone cysts (synovial fluid forced through fibrillated cartilage into exposed bone)
    D. joint mice - dislodged pieces of cartilage and bone
    E. eburnation - complete loss of cartilage –> bone on bone –> bone becomes polished like ivory
  4. Clinical - swollen, hard joints
    - symptoms and signs related to damage, not inflammation (no inflammatory synovial fluid)
    - <30 min morning stiffness
    - pain increases with use (ie at end of day)
    - asymmetric and slowly progressive - only few joints symptomatic
    - deep, dull aching pain
    - NO systemic symptoms (fever, anemia, weight loss)
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27
Q 
[Osteoarthritis]
Risk factors and diagnosis of the following types of osteoarthritis: 
1. Knee
2. Hip
3. Hand
A
  1. Knee
    A. Risk factors - obesity (weight-bearing joint), age
    B. Diagnosis - can diagnose without X-rays
    - symptoms: knee pain, functional limitation, AM stiffness
    - signs: crepitus, decreased ROM, bony enlargement
    - medial cartilage lost first –> varus stress –> bow-legged
  2. Hip
    A. Risk factors -
    - avascular necrosis of femoral head (medial circumflex femoral artery) - due to corticosteroids, alcohol, sickle cell, trauma
    - Legg-Calve-Perthes (idiopathic avascular necrosis of femoral head in obese male children)
    - slipped capital femoral epiphysis (in obese male children)
    B. Diagnosis - hip pain + at least 2 of following:
    - passive external rotation –> decreased ROM and pain on internal rotation
    *passive internal rotation –> posterior hip dislocation
    - low RBC sedimentation rate (no inflammation)
    - X-ray showing osteophytes and joint space narrowing
  3. Hand
    A. Risk factors - female, age
    B. Diagnosis - involves PIP (Bouchard nodes) and DIP (Heberden nodes)
    *prOximal - BOuchard
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28
Q 
[Rheumatoid arthritis]
RA
1. Epi / risk factors
2. Pathophysiology
3. Diagnosis
A

Rheumatoid arthritis

  1. Epi / risk factors - most common persistent inflammatory arthritis
    - female middle-aged (autoimmune)
    - genetics: HLA-DR4, family history
    - environmental: smoking, silica
  2. Pathophysiology - autoimmune Type IV HSN
    - anti-cyclic citrullinated peptide antibodies ACPA –> inflammatory cells infiltrate synovial membrane –> CD4+ T cells stimulate B cells and macrophages:
    - B cells produce rheumatoid factor (IgM Ab against patient’s IgG Fc region)
    - macrophages produce TNFalpha –> pro-inflammatory cytokines
    - -> formation of pannus (synovium becomes thickened with villous projections) –> erodes bone and cartilage
  3. Diagnosis
    - antibodies: rheumatoid factor, ACPA (more specific), ANA
    - non-specific inflammation markers: ESR, C-reactive protein
    - hematologic: anemia of chronic disease
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29
Q 
[Rheumatoid arthritis]
RA
4. Pathologic features
5. Clinical presentation
6. Extra-articular manifestations
A
  1. Pathologic features
    - osteopenia adjacent to joint (Decreased bone mass but not to the extent of osteoporosis)
    - proliferative synovitis with inflammatory infiltrate (lymphocytes, macrophages) –> activates osteoclasts –> osteoporosis (bone loss –> Decreased bone mass)
    - deformities: ulnar finger deviation, swan neck (PIP extension, DIP flexion), boutonniere (PIP flexion, DIP extension)
    - cervical subluxation - esp with neck flexion, C1-C2 vulnerable bc affects upper cervical spine
  2. Clinical presentation - swollen, boggy joints (due to swelling, tenderness, warmth)
    - systemic symptoms (fever, weight loss, fatigue) due to cytokine release
    - morning stiffness (~1 hour) and pain that improve with use
    - symmetric - affects upper cervical spine and small joints of hands and feet, esp MCP and PIP but not DIPs
  3. Extra-articular manifestations
    - rheumatoid nodules (central fibrinoid necrosis with palisading macrophages) on extensor surfaces e.g. olecranon, proximal ulna
    Caplan syndrome = pneumoconiosis + rheumatoid nodules in lung
    - cardiac - pericardial effusion, pericarditis
    - pulmonary - pleuritis, effusions, interstitial lung disease
    - ocular - dry eye, Sjogren’s
    - Felty syndrome - SANTA –> Splenomegaly, Anemia of chronic disease, Neutropenia, Thrombocytopenia, + Arthritis (rheumatoid)
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30
Q

[Paget disease]

  1. Epi / risk factors
  2. Pathophysiology
  3. Pathologic features
  4. Clinical
  5. Treatment
  6. Complications
A

Paget Disease - focal disorder of bone metabolism

  1. Epi - onset in old age
    - risk factors: western european descent, age, M>F
    - etiology unknown, perhaps viral (paramyxovirus)
  2. Pathophysiology
    A. Osteolytic stage - osteoclast&raquo_space; osteoblast activity; osteoclasts hyper-responsive to D3, RANKL and have more nuclei than usual (up to 100)
    B. Mixed - osteoclast and osteoblast activity
    C. Osteosclerotic - osteoblasts make thick, sclerotic bone that fractures easily
  3. Pathologic features
    - main sites are pelvis, skull, lumbar spine, femur
    - isolated ↑ ALP (normal GGT, calcium, phosphate, PTH, Vitamin D)
    - “jigsaw” mosaic pattern of woven and lamellar bone (rapid bone turnover) that is disorganized, poorly mineralized, lacks structural integrity
  4. Clinical
    - most patients are asymptomatic
    - pain due to bone overgrowth and microfractures
    - deformity –> bowing of limb, increased skull size (hat size enlarged), lion-like facies
    - hearing loss due to auditory foramen narrowing (temporal bone)
  5. Treatment
    - bisphosphonates (induce osteoclast apoptosis and block osteoclast activity, but can lead to osteonecrosis of the jaw)
  6. Complications
    - high output heart failure - due to formation of AV shunts in bone (Pagetic bone very vascular)
    - ↑ risk osteosarcoma
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31
Q 
[Bone/Joint infections]
Septic arthritis
1. Risk factors
2. Etiology by age group
3. Diagnosis
A

Septic arthritis

  1. Risk factors - joints have hyaline cartilage –> susceptible to infection bc relatively avascular –> immune cells cannot access easily
    - prosthetic joints
    - elderly
    - immunosuppressed
    - previous joint pathology - RA, osteoarthritis, gout, sickle cell disease
2. Etiology
A. children <2 yo --> H. influenza / Kingella (both are part of HACEK group - Gram (-) coccobacilli that also cause endocarditis) 
B. Young adults - Neisseria gonorrhea 
C. Adults - Staph aureus, epidermidis
D. Sickle cell (any age) - salmonella
  1. Diagnosis - joint aspiration, DDx includes gout and pseudogout –> increased WBC count, no crystals
    * immediate diagnosis necessary bc can rapidly destroy joint
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32
Q 
[Bone/Joint infections]
Septic arthritis
4. Pathogenesis
5. Clinical 
6. Treatment
A
  1. Pathogenesis - microorganisms invade joint space –> activates acute inflammation –> neutrophil response –> proteolytic enzymes –> damage articular cartilage, bone, joint capsule
    - hematogenous spread MCC - synovium lacks basement membrane, easier for bacteria to gain access to joint space
    - traumatic inoculation eg cat bite
  2. Clinical - acute monoarticular arthritis, usually at knee or hip
    - joint is red, swollen, warm, tender, with impaired ROM
    - fever
    * inflammation of eyes, skin –> reactive arthritis (not septic)
  3. Treatment - medical emergency!
    - aspiration + antibiotics
    - glucocorticoids, colchicine (microtubule inhibitor)
33
Q 
[Bone/Joint infections]
Bacterial infections that cause arthritis
1. Neisseria gonorrhea
2. Borrelia burgdorferi
3. Mycobacterium tuberulosis
A
  1. Neisseria gonorrhea –> Gram (-) diplococci that causes disseminated gonococcal infection; joint tap negative bc bacteria is intracellular (in neutrophils)
    - fever, chills, malaise first
    A. Migratory polyarthritis - asymmetric, can lead to septic arthritis… or
    B. Triad - Tenosynovitis (hand) + dermatitis (painful, tender necrotic pustules) + polyarthralgia
  2. Borrelia burgdorferi –> spirochete (spiral bacteria) spread by ixodes scapularis tick that causes Lyme disease (3rd stage)
    A. Chronic inflammatory synovitis - immune-mediated
    B. migratory polyarthritis - progressive, commonly in knee
    - also causes CNS issues (confusion, encephalopathy)
  3. Mycobacterium tuberculosis - Gram (+) rod that causes tuberculosis
    A. Chronic granulomatous monoarthritis - progressive, affects weight-bearing joints eg hips, knees
    B. Potts disease - osteomyelitis of vertebral bodies
34
Q 
[Bone/Joint infections]
Viral infections that cause arthritis
1. Rubella virus
2. Mumps virus
3. Parvovirus B19
A
  1. Rubella virus - enveloped (+) sense RNA virus
    A. Congenital (TORCHeS) - PDA, sensorineural deafness, cataracts, blueberry muffin rash
    B. Children - descending maculopapular rash
    C. Adult - arthritis, fever
  2. Mumps virus - enveloped (-) sense RNA virus
    A. Parotitis –> can lead to self-limited polyarthritis
  3. Parvovirus B19 - naked, ssDNA virus
    A. Children - Fifth disease (slapped cheek rash)
    B. Adult - joint pain, arthritis
35
Q 
[Bone/Joint infections]
Osteomyelitis 
1. Causes
2. Pathophys
3. Clinical
A

Osteomyelitis

  1. Causes - bone normally resistant to bacterial colonization, orthopedic hardware
    A. Trauma - MVA, sports injury
    B. Vascular insufficiency - due to trauma or diabetes
    C. Hematogenous seeding after bacteremia
    - Staph aureus (at all ages)
    - Pseudomonas (IVDU and diabetics)
    - Salmonella (sickle cell patients)
    - others: Brucella (unpasteurized milk), Pasteurella (cat and dog bites), Blastomycoses
  2. Pathophys - commonly infects metaphysis where blood supply penetrates –> impairs blood supply –> bone necrosis
    - dead bone = sequestrum
    - shell of new bone around necrotic infected bone = involucrum
    - most commonly affected are vertebrae
  3. Clinical - acute systemic illness
    - throbbing pain, erythema over affected region with decreased ROM and inability to bear weight
    - X-ray - lytic focus surrounded by sclerosis
36
Q

[SnSA]
Seronegative spondylarthropathies
1. Diseases
2. Characteristic features incl extrasynovial manifestations

A

Seronegative spondylarthropathies - group of systemic inflammatory joint disorders that are not rheumatoid factor Ab positive
- associated with HLA-B27 (MHC Class I serotype)

1. Diseases - PAIR 
Psoriatic arthritis
Ankylosing spondylitis
IBD-associated spondyloarthropathy
Reactive arthritis (prev Reiter's syndrome)
  1. Characteristic features
    A. involves axial skeleton (spine and sacroiliac joints) –> morning stiffness that improves with movement
    - loss of lumbar lordosis, accentuated kyphosis
    - Schober test - decreased spine mobility

B. asymmetric oligoarthritis (1-4 joints) - usually involves lower extremities

C extrasynovial inflammation (outside joint space)

i. enthesitis - inflammation at sites of insertions of ligaments, tendons, and joint capsule –> there is bone erosion (like in RA) but leads to new bone formation (unlike in RA)
- most commonly seen at achilles tendon
ii. dactylitis - flexor tenosynovitis “sausage digit”
iii. anterior uveitis - iris and ciliary body –> eye pain, blurred vision, photophobia –> can cause blindness

37
Q 
[SnSA]
Ankylosing spondylitis
1. Epi
2. Pathologic features
3. Clinical
A

Ankylosing spondylitis

  1. Epi - white males 15-40 yo
    - HLA-B27 (+)
    - family history
  2. Pathologic features - symmetric involvement of spine and sacroiliac joints
    - syndesmophytes - new bone that bridges adjacent vertebral bodies and fuses joints (anklyosis) –> “bamboo spine” on X-ray
  3. Clinical - slowly progressive
    - dull, aching lower back pain, worse in AM and improves with exercise, radiates to buttocks
    - sacroiliac joint tenderness - first involved
    - uveitis - most common extra-articular manifestation
    - enthesitis
    - peripheral arthritis - large joints (hips); no dactylitis
    - ascending aortitis –> dilation of aortic ring –> aortic insufficiency / regurgitation
    - limited chest wall expansion –> hypoventilation
38
Q 
[SnSA]
Reactive arthritis 
1. Epi
2. Pathologic features
3. Clinical
A

Reactive arthritis, prev known as Reiter syndrome

  1. Epi - inflammatory arthritis triggered by infectious agent outside the joint –> Chlamydia trachomatis or enteric (Campylobacter, Shigella, Salmonella, Yersinia)
    - HLA-B27 (+)
  2. Pathologic features - TNFalpha is inflammatory mediator
  3. Clinical - “can’t see, can’t pee, can’t climb a tree”
    - conjunctivitis - milder than uveitis
    - urethritis
    - oligoarthritis - lower extremity, asymmetric
    - dermatologic manifestation: circinate balanitis (annular dermatitis of glans penis) + ketatoderma blennorhagica (scaly rash on hands and soles of feet)
39
Q 
[SnSA]
Psoriatic arthritis 
1. Epi
2. Pathologic features
3. Clinical
4. Differentiation from RA
A

Psoriatic arthritis

  1. Epi - seen in 1/3 of patients with psoriasis
    - HLA-B27 (+)
    - family history
  2. Pathologic features
    - extrasynovial inflammation –> T cell (CD4 and CD8) and TNFalpha mediated inflammation of synovium (Secondary)
    - “pencil-in-cup” deformity of DIP on X-ray
  3. Clinical
    - small joint polyarthritis
    - dactylitis “sausage fingers”
    - nail involvement - nail pitting, oncholysis (detachment of nail from nail bed)
    - osteolytic destruction of IP joints and new bone formation
    - erosive arthritis (arthritis mutilans) with telescoping of digits
  4. Differentiation from RA (both are small joint polyarthritises)
    - negative for rheumatoid factor
    - no subcutaneous rheumatoid nodules
    - asymmetric (RA Is symmetric joint involvement)
    - DIP involvement (RA does not involve DIPs)
40
Q 
[SnSA]
IBD-associated spondyloarthropathy
1. Epi
2. Pathologic features
3. Clinical
A

IBD-associated spondyloarthropathy

  1. Epi - increased risk with presence of other extraintestinal manifestations (aphthous ulcers, pyoderma gangrenosum, erythema nodosum, uveitis)
    - HLA-B27 (+)
  2. Pathologic features
    - Crohn’s&raquo_space; UC
  3. Clinical
    - asymmetric lower extremity - arthritis that tracks with the GI disease
    - abrupt onset, migratory, subsides in a few months but can recur
    - can have spondylitis (spine involvement) - independent of the GI disease
41
Q

[Crystal arthropathies]
Gout
1. Epi / risk factors

  1. Purine degradation
  2. Etiology
    A. Primary
    B. Secondary
A

Gout - monosodium urate (MSU) crystals

  1. Epi - most common acute inflammatory arthritis, due to hyperuricemia (>6.8 mg/dL)
    A. risk factors: M>F, alcohol, obesity, meat consumption
    - iatrogenic - pyrazinamide (TB), thiazide diuretics, baby aspirin
  2. Purine metabolism
    A. Adenosine + (adenosine deaminase ADA) –> inosine –> hypoxanthine
    *ADA deficiency –> SCID
    B. Guanosine –> guanine + (guanine deaminase) –> xanthine
    C. Liver: Hypoxanthine + (xanthine oxidase) –> xanthine + (xanthine oxidase) –> uric acid i.e. urate
    D. Urate excreted in kidneys (70%) and gut (30%)
  3. Etiology
    A. Primary (90%) - hyperuricemia due to urate underexcretion by kidney PCT
    - net 10% excretion
    B. Secondary (10%) - urate overproduction due to known underlying disease –> rapid cell turnover (myeloproliferative disorders), chemo, renal failure, lead poisoning, congenital deficient HGPRT (Lesch-Nyhan)
42
Q

[Crystal arthropathies]
Gout
4. Pathophysiology

  1. Pathologic features
  2. Clinical
    A. Early
    B. Advanced
A
  1. Pathophys - MSU crystals in joint –> phagocytosed by synovial cells –> inflammasome releases cytokines (IL-1), prostaglandins, and lysosomal enzymes –> inflammatory response mediated by neutrophils and macrophages –> tissue injury
  2. Pathologic features
    - PMN (neutrophil) infiltration of synovium
    - monosodium urate crystals in synovium –> needle-shaped, negative birefringence in polarized light (yellow in parallel, blue under perpendicular light)
  3. Clinical
    A. Early - begins as acute monoarticular event (MTP of big toe) but can spread to more joints over time
    - attacks at night or early morning, abrupt onset
    - joints red, swollen, and painful
    B. Advanced - interval shortens
    - tophi (chalky MSU crystal deposits in the soft tissue) pathognomonic - on ear, olecranon, achilles tendon
    - risk of uric acid kidney stones (rhomboid shape, radiolucent, low urine pH)

*DD is septic arthritis

43
Q 
[Crystal arthropathies]
Pseudogout
1. Epi / risk factors
2. Pathophysiology
3. Pathologic features
4. Clinical
A

Pseudogout = Calcium pyrophosphate deposition disease (CPPD)

  1. Epi - M=F, age >50
    - Risk factors: hemachromatosis, hyperparathyroidism, joint trauma/injury
  2. Pathophysiology - disorder of chondrocytes that produce cartilage –> dysregulation of phosphate metabolism
  3. Pathologic features
    - deposits in articular cartilage joint space (NOT soft tissue, as with gout)
    - crystals in synovial fluid
    - chondrocalcinosis (cartilage calcification) on X-ray
    - crystals are rhomboid and weakly positively birefringent under polarized light (blue when parallel to
    light)
  4. Clinical - knee most commonly affected
    A. pseudogout - acute pain and swelling with inflammation
    B. pseudoarthritis - chronic degeneration
44
Q 
[Gout treatment]
Describe MOA, indications, and adverse effects /  contraindications
1. NSAIDs
2. Colchicine
3. Corticosteroids
A
  1. NSAIDs - indomethacin, ibuprofen, naloxen, celocoxib
    A. MOA - inhibit COX-mediated prostaglandin synthesis
    B. Indications - first line for acute gout episodes
    C. Contraindicatiosn - aspirin/salicylates contraindicated bc they inhibit uric acid secretion at low doses
  2. Colchicine
    A. MOA - binds intracellular tubulin –> prevents polymerization into microtubules of spindle apparatus –> cytoskeleton disruption inhibits neutrophil and macrophage migration and phagocytosis
    B. Indications - for acute gout episodes in pts with contraindications to NSAIDs (eg renal failure, PUD)
    C. Adverse effects - burning throat pain, diarrhea, nausea, vomiting, abdominal pain
  3. Corticosteroids - oral prednisone (systemic) or intraarticular therapy
    A. MOA - regulate gene transcription to inhibit NFkB (transcription factor for pro-inflammatory cytokines e.g. IL-2, TNFalpha) –> prevent production of neutrophil adhesion molecules, inhibit B and T cells –> reduce inflammation
    B. Indications - acute gout flares if contraindications to NSAIDs, colchicine
    C. Adverse effects - ↑ serum glucose, hypokalemia, cushing syndrome
45
Q

[Gout treatment]
Describe MOA, indications, and adverse effects / contraindications
4. Allopurinol, Febuxostat

A
  1. Allopurinol, Febuxostat

A. MOA

i. Allopurinol - purine analog that is a suicide inhibitor –> irreversibly inhibits xanthine oxidase and converted into alloxanthine, which is soluble
ii. Febuxostat - nonpurine irreversible inhibitor of xathine oxidase

B. Indication - first-line for chronic gout in intercritical period
- pts with tophaceous gout, renal failure, recurrent renal stones

C. Contraindication - during an attack

D. Adverse effects

  • acute gouty attacks when urate crystals are being withdrawn from tissues –> give with NSAID or colchicine until serum urate < 6 mg/dL
  • GI intolerance –> take with food
    i. allopurinol- Stevens-Johnson syndrome (toxic epidermal necrolysis)
  • DRESS syndrome (Drug Reaction with Eosinophilia and Systemic Symptoms)
    ii. febuxostat - better safety profile
46
Q

[Gout treatment]
Describe MOA, indications, and adverse effects / contraindications
5. Probenecid
6. Pegloticase

A
  1. Probenecid
    A. MOA - organic acid that decreases renal reabsorption of uric acid at PCT –> increases secretion of uric acid and decreases reabsorption
    B. Indication
    - for urate underexcreters who have tophi or increasingly frequent attacks
    C. Contraindication - sulfa allergies, aspirin (inhibits urate transporter)
    - overexcreters –> can precipitate renal calculi
    D. Adverse effects
    - increased risk for renal stones (keep urine pH > 6)
    - probenecid prevents renal excretion of other drugs e.g. penicillin, NSAIDs
  2. Pegloticase (IV biologic)
    A. MOA - uricase that converts uric acid to allantoin (water soluble)
    B. Indication - chronic gout refractory to standard therapy
    C. Adverse effects - anaphylactic reaction to IV infusion
    - can cause hemolysis in G6PD deficiency
47
Q

[SLE]

  1. Epi
  2. Etiology
  3. Pathogenesis
  4. Markers and clinical associations
A

Systemic lupus erythamatosus (SLE)

  1. Epi - females of reproductive age, African american predisposition
  2. Etiology - genetics, environment (UV light exposure), immunologic (failure of self-tolerance in B and CD4+ T cells)
  3. Pathogenesis - loss of self-tolerance due to defects in apoptotic clearance –> production of anti-nuclear antibodies –> deposition of Ab-Ag immune complexes (Type III HSN) –> inflammatory response and activation of macrophages and neutrophils –> tissue damage and fibrosis
  4. Markers
    - antinuclear antibodies (ANA) - sensitive
    - anti-dsDNA Ab - IgG, very specific, poor prognosis (fluctuate with disease activity), associated with renal disease eg RPGN
    - Anti-Smith Ab - specific, but not prognostic (always elevated)
    - anti-histone Ab - specific for drug-induced lupus
  • ↓ C3, C4, and CH50 due to immune complex deposition –> IF shows granular deposition of IgG-C3 along basement membrane
  • autoantibodies can develop against RBCs, WBCs, and platelets
  • antiphospholipid (anticardiolipin) antibodies can develop –> associated with recurrent venous thrombosis or pregnancy loss
48
Q

[SLE]
5. Clinical presentation - triad
6. Explain the acronym
RASHORPAIN

A
  1. Clinical presentation - triad in young woman: butterfly rash, joint pain, fever
  2. RASHORPAIN
    Rash - malar (butterfly, spares nasolabial folds) pathognomonic or discoid (leaves scars, Seal had it)
    Arthritis - symmetric polyarthritis with deformities due to tendon inflammation –> Jaccoud arthropathy (deforming non-erosive arthritis with ulnar deviation of fingers), swan neck –> CAN be reduced
    Serositis –> pericarditis - pleuritic chest pain (on inspiration) + pleural friction rub
    Hematologic - cytopenias due to autoAb
    Oral/nasopharyngeal ulcers - painless
    Renal disease - membranous nephropathy, DPGN (with crescents due to epithelial cells in Bowman’s space)
    Photosensitivity
    Antinuclear antibodies (ANA)
    Immunologic disorder (anti-dsDNA, anti-Smith, antiphospholipid)
    Neurologic disorders - cognitive dysfunction, seizures, psychosis

+ fatigue, hair thinning (alopecia), Raynaud

49
Q

[SLE]

  1. Libman-Sacks endocarditis
  2. MCC causes of death in SLE
  3. Compare to drug-induced lupus
A
  1. Libman-Sacks endocarditis (LSE in SLE) - sterile (non-bacterial) verrucous (warty) platelet vegetations on undersurface of mitral or aortic valves –> embolic thrombi
  2. MCC causes of death in SLE:
    - renal disease - kidney is most commonly involved visceral organ –> DPGN common cause of death
    - cardiovascular disease (chronic inflammation –> premature atherosclerosis)
    - infections
    - pulmonary - pleuritis –> chest pain + pleural effusion (dullness to percussion, decreased tactile fremitus, decreased breath sounds
  3. Drug-induced SLE
    - caused by Sulfa drugs, Hydralazine, Isoniazid, Procainamide, Phenytoin, Etanercept
    - white > black, F=M
    - anti-histone Ab, normal levels of complement
    - kidneys rarely involved
50
Q 
[SLE]
Scleroderma
1. Epi 
2. Pathogenesis
3. Clinical 
4. Diffuse vs limited (CREST syndrome)
A

Sclerodema = Systemic sclerosis

  1. Epi - autoimmune, F»M
    - ANA (+)
  2. Pathogenesis - endothelial injury –> immune activation and CD4 T cells activated –> activation of inflammation and fibrosis –> sclerosis and damage to vasculature
    - destruction of capillaries, peripheral arteries throughout the body –> thickened intima, narrowed lumen –> occlusion of vessel
  3. Clinical - skin thickening due to fibrosis of dermis, collagen deposition –> loss of joint mobility
    - swollen fingers, arthralgias
    - puffy, taught skin without wrinkles
    - finger pitting with distal ulcerations
  4. Diffuse vs limited
    A. Diffuse - rapid progression, widespread skin involvement, associated with anti-Scl-70 Ab (anti-DNA topoisomerase I)

B. Limited - more benign course and limited to fingers and face, one form is CREST syndrome

  • Calcinosis (calcium deposits) and anti-Centromere Ab
  • Raynaud phenomenon first presentation
  • Esophageal dysmotility - all pressures low –> GERD
  • Sclerodactyly - thickened skin forces fingers to retract (no problem with the joints, deformities are reducible)
  • Telangiectasia (dilated bv)
51
Q

[SLE]
Scleroderma
5. Raynaud disease vs syndrome

  1. Systemic
    A. Pulmonary
    B. GI
    C. Renal
A
  1. Raynaud phenomenon - overexaggerated vasoconstriction of small vessels in response to cold or stress; fingers go from white –> blue –> red
    A. Raynaud disease - idiopathy, symmetric, in young women and no evidence of microvascular disease
    B. Raynaud syndrome - secondary to SLE, CREST; asymmetric, painful, can lead to digital ulceration
  2. Systemic
    A. Pulmonary - MCC death in scleroderma
    i. interstitial fibrosis –> associated with diffuse subtype
    ii. pulmonary arterial hypertension - loud P2, RV heave, tricuspid regurg (right side dilates due to increased load) –> associated with limited subtype
    B. GI - general bowel dysmotility due to smooth muscle atrophy, can have SIBO
    C. Renal - scleroderma renal crisis (anti-RNA polymerase III Ab) = rapid renal impairment, can lead to malignant hypertension
    - arteriolar vasculopathy –> onion-skinning (due to malignant renal hypertension), thrombotic vascular occlusion, glomerular ischemic collapse
    - prevent with ACEIs
52
Q 
[SLE]
Sjogren syndrome
1. Epi 
2. Markers
3. Pathogenesis
3. Clinical presentation
A

Sjogren syndrome
1. Epi - females 40-60 years old

  1. Markers - systemic autoimmune disorder –> autoantibodies
    - Anti-Ro / SS-A
    - Anti-La / SS-B
    - also ANA, rheumatoid factor
  2. Pathogenesis - lymphocytic infiltrates –> destruction of exocrine glands, especially lacrimal and salivary
    - increased risk of MALToma
  3. Clinical
    - xerostomia - dry mouth due to ↓ saliva production –> dental caries, difficulty speaking, oral candidiasis
    - xerophthalmia - dry eyes due to ↓ tear production –> corneal ulcers
    - bilateral parotid gland enlargement
    - inflammatory joint pain
53
Q

[NSAIDs]
MOA, adverse effects of
1. glucocorticoids
2. Traditional NSAIDs

A
  1. glucocorticoids
    A. MOA - inhibit phopholipase (PLA2) - prevent conversion of phospholipids into arachidonic acid (precursor to LOX and COX pathways)

B. Adverse effects - Cushingoid

  • ↑ serum glucose levels (inhibits glucose uptake by muscle cells, stimulates gluconeogenesis in liver)
  • ↑ lipolysis and fat deposition (stimulates hormone-sensitive lipase)
  • muscle wasting and osteoporosis (stimulates protein catabolism)
  1. NSAIDs - analgesic, anti-pyretic, anti-inflammatory
    A. MOA - inhibit COX (differ in COX1 vs COX2 selectivity) –> prevent conversion of arachidonic acid to prostaglandins
    i. COX1 in platelets (housekeeping, constitutively expressed) –> thromboxane (TXA2) –> platelet activator + vasoconstrictor, gastric protection
    ii. COX2 on vascular endothelium (induced by inflammation) –> prostacyclin (PGI2) –> vasodilation, inhibits platelet aggregation, induces fever

B. Adverse effects

  • GI disturbances - ulcers (MCC after H. pylori); administer with PPI
  • bleeding - increased COX2 pathway reduces thrombosis; prolonged bleeding time
  • interferes with renal function - decreases GFR and RBF –> renal papillary necrosis, acute interstitial nephritis
  • increases serum Lithium concentrations, aplastic anemia
54
Q 
[NSAIDs]
Compare and contrast MOA, indications, and adverse effects of: 
1. Acetaminophen
2. Aspirin
3. non-selective NSAIDs
4. Celecoxib
A
  1. Acetaminophen
    A. MOA - unknown, reversible COX2>1 inhibition
    B. Indications - pain, fever (NOT anti-inflammatory)
    C. Adverse effects - metabolized by CYP450 in liver, toxic metabolite NAPQI is inactivated by glutathione
    - overdose –> ↑ NAPQI –> liver damage; give activated charcoal or N-acetylcysteine (restores glutathione)
  2. Aspirin
    A. MOA - irreversibly inhibits COX1 and COX2, is weakly more selective for COX1 –> reduces risk of thrombosis via COX2 pathway
    B. Indications
    - low-dose –> anti-thrombotic (baby aspirin to prevent MI)
    - high dose –> pain, fever, inflammation, Kawasaki disease
    C. Adverse effects - ulcers, bleeding, Reye syndrome in kids
  3. non-selective NSAIDs - ibuprofen, naproxen, diclofenac, indomethacin
    A. MOA - reversibly inhibit COX1 and 2
    B. Indications - pain, fever, inflammation
    C. Adverse effects - GI toxicity, renal toxicity in elderly (AIN, renal papillary necrosis)
  4. Celecoxib
    A. MOA - reversibly inhibit COX2
    B. Indications - RA, OA
    C. Adverse effects - increased COX1 platelet aggregation –> increased risk of thrombosis (why so many were pulled off the market)
55
Q

[DMARDs]
Describe targets and indications of:

1. Non-biologic DMARDs
A. methotrexate
B. leflunomide
C. sulfalazine
D. hydroxychloroquine
A

DMARDs = Disease-Modifying Anti-rheumatic Drug

  1. Non-biologic DMARDs
    A. methotrexate - competitively inhibits DHFR –> suppresses B and T cell function
    - treats RA (first-line), psoriasis, psoriatic arthritis, polymyositis, SLE + leukemias, lymphomas, sarcomas, ectopic pregnancy
    - supplement with folic acid, myelosuppression reversible with leucovorin rescue
    - can cause megaloblastic anemia, pulmonary fibrosis

B. leflunomide - inhibits dihydroorate dehydrogenase (pyrimidine synthesis) –> induces cell cycle arrest of activated lymphocytes

  • treats RA, psoriatic arthritis
  • teratogenic, diarrhea, hypertension, hepatotoxicity

C. sulfasalazine - activated by colonic bacteria

  • treats UC, RA
  • sulfa drug

D. hydroxychloroquine - MOA unknown, originally indicated for malaria treatment + prevention; treats RA, lupus
- can cause myopathy

56
Q 
[DMARDs]
Describe targets and indications of: 
2. Biologic DMARDs
A. etanercept 
B. infliximab
C. adalimumab
D. rituximab 
E. tocilizumab
F. abatacept
  1. DMARD adverse effects and contra-indications
A
  1. Biologic DMARDs
    A. etanercept - fusion protein that is a decoy TNFalpha receptor + IgG
    - treats RA, psoriasis, ankylosing spondylitis - pts unresponsive to traditional DMARD therapy
    - can cause lupus-like syndrome

B. infliximab (Remicade) - chimeric Ab against TNFalpha

  • treats Crohn, UC, RA, ankylosing spondylitis, psoriasis
  • hepatotoxicity

C. adalimumab (Humira) - human Ab against TNFalpha

  • treats Crohn, RA, ankylosing spondylitis, psoriasis
  • pts unresponsive to traditional DMARD therapy

D. rituximab - Ab against CD20+ B cells

  • treats RA (also ITP, CLL, B-cell NHL)
  • increased risk of progressive multifocal leukoencephalopathy

E. tocilizumab - Ab against IL-6 - binds to both soluble and membrane bound IL-6 receptors
- treats RA

F. abatacept - CTLA4-Ig fusion that inhibits binding of CD80 and CD86 to CD28 –> inhibits T cell activation
- treats refractory RA

3A. Adverse effects - injection/infusion rxns
B. Contraindications - active infection, treat TB first (otherwise latent TB will reactivate), pre-existing demyelinating disorders, pregnancy

57
Q

[Skin pathology]
Epidermal tumors - causes, location, appearance
1. Suborrheic keratosis
2. Actinic keratosis

A
  1. Suborrheic keratosis - benign epidermal tumors in the elderly
    A. Cause - FGFR3 mutation
    - sudden onset of many (Leser-Trelat sign) –> paraneoplastic syndrome for GI cancer e.g. gastric adenocarcinoma
    B. Location - arise spontaneously on trunk
    C. Appearance - velvety, stuck-on; sharply demarcated
    - hyperkeratosis (thickening of corneal layer)
    - small keratin-filled horn pseudocysts and invagination cysts
  2. Actinic keratosis
    A. Cause - sun-exposure in light-skinned people
    - premalignant for squamous cell carcinoma
    B. Location - sun-exposed eg face, hands
    C. Appearance - scaly, rough irregular plaques that are sandpapery with hyperkeratosis
58
Q 
[Skin pathology]
Epidermal tumors - causes, location, appearance
3. Basal cell carcinoma
4. Squamous cell carcinoma
- precursors, variants
A
  1. Basal cell carcinoma - most common skin cancer
    A. Cause - DNA damage due to exposure to UVB light
    - locally invasive but rarely metastasize
    B. Location - sun-exposed areas, classically on upper lip
    C. Appearance - pink, pearl-like papules with central, ulcerated crater surrounded by dilated vessels (telangiectasias) and rolled borders
    - or nonhealing ulcers with infiltrating growth, or scaling plaques
    - histology - nests of basal cells with peripheral palisading nuclei
  2. Squamous cell carcinoma - second most common
    A. Cause - DNA damage due to exposure to UVB light, immunosuppression, arsenic exposure, chronic non-healing wound (e.g. scar from burn, draining sinus tract)
    - locally invasive but rarely metastasize, can spread to lymph nodes
    B. Location - classically on lower lip but also on face, neck, hands
    C. Appearance - scaly, red plaque with ulceration or bleeding
    - histology - keratin pearls *looks same no matter where it occurs (SCC of lung, cervix, etc)
    D. Precursor - actinic keratosis (scaly plaque) on face, back, neck
    - also carcinoma in situ (full thickness but does not invade BM)
    E. Variant - keratoacanthoma - grows rapidly in 6 weeks but may regress spontaneously over months; cup-shaped with keratin debris in the center
59
Q 
[Skin pathology]
Pigment disorders
1. Vitiligo
2. Albinism
3. Melasma
A
  1. Vitiligo
    A. Cause - autoimmune destruction of melanocytes (stratum basale of epidermis)
    B. Appearance - Irregular areas of complete depigmentation
  2. Albinism
    A. Cause - AR absence of tyrosinase or defective tyrosine transport –> cannot make melanin from tyrosine
    - normal number of melanocytes but inability to produce melanin
    - increased risk skin cancer (cannot protect against UVB)
    B. Appearance - white hair, white or pink skin, blue eyes, impaired vision / photophobia
  3. Melasma
    A. Cause - UV radiation, estrogen –> pregnancy (“mask of pregnancy”, OCPs
    B. Appearance - increased # melanocytes –> increased melanin deposition –> large hyperpigmented macules that do not fade
60
Q 
[Skin pathology]
Nevi 
1. Congenital melanocytic nevi
2. Junctional vs compound vs intradermal nevi
3. Dysplastic nevus
4. Dysplastic nevus syndrome
A

Nevi - get smaller and lose tyrosinase as they mature

  1. Congenital melanocytic nevi - benign neoplasm of melanocytes; often have hair
    - larger ones have increased risk of melanoma devlpt

2A. Junctional nevi - macules (flat lesions); clusters of melanocytes at dermal-epidermal junction; more common in children
B. Compound nevi - raised, dome-shaped papules; clusters of melanocytes in epidermis and dermis
C. Intradermal - raised, dome-shaped papules; only in dermis; most common in adults

  1. Dysplastic nevus - direct precursor for melanoma
    - pigmented raised lesion with central darker shade and irregular border; junctional cluster of irregular melanocytes
  2. Dysplastic nevus syndrome
    A. Cause - AD mutation on CDKN2A (tumor suppressor that is a negative regulator of CDK4) –> lose regulation of cell cycle
    B. Appearance - multiple dysplastic nevi –> several melanomas
61
Q 
[Skin pathology]
Pigment disorders - Melanoma
1. Normal function
2. Risk factors
3. Appearance
4. Types
A

Melanoma

  1. Melanocytes - neural crest-derived cells in basal layer of epidermis
    - produce melanin from tyrosine in melanosomes
    - pass melanosomes to keratinocytes –> skin pigmentation
  2. Risk factors - exposure to UV radiation, family history
    - BRAF V600E mutation –> activating mutation in BRAF kinase –> can treat with vemurafenib
    - BRAF gain of function mutation (RAS pathway) –> CDK inhibitor loss of function –> vertical growth potential
    - risk of metastasis to lung, liver, or brain –> prognosis = depth of tumor
    - S-100 tumor marker (neural crest origin)
3. Appearance - ABCDE
Asymmetry
Border irregularity
Color variation
Diameter > 6 mm
Evolution - changes in size, shape, color over time
  1. Types
    A. Superficial spreading - most common, radial growth (good prognosis)
    B. Nodular - early vertical growth –> worst prognosis
    C. Lentigo maligna - on face in older patients; radial growth
    D. Acral lentiginous - least common, on palms and soles; seen in darker-skinned
62
Q

[Skin pathology]
Blistering lesions - cause, appearance, clinical
1. Pemphigus vulgaris
2. Bullous pemphigoid

A
  1. Pemphigus vulgaris
    A. Cause - autoimmune - IgG antibodies against desmogleins (component of desmosomes) –> acantholysis (separation of epidermal cells) - separation of keratinocytes in stratum spinosum of epidermis (normally are connected by desmosomes)
    B. Appearance
    - basal cells still attached to basement membrane –> tombstones on histology
    - reticular net-like pattern of Ab around epidermal cells on immunofluorescence
    C. Clinical
    - painful flaccid intraepidermal bullae (blisters filled with fluid) on normal skin
    - mucosal involvement esp oral cavity - ulcerations
    - Nikolsky sign positive –> skin blisters peel if you stroke skin normally
  2. Bullous pemphigoid
    A. Cause - autoimmune - IgG antibodies against bullous phemphigoid antigens (BPAs) in hemidesmosomes in epidermis basement membrane
    B. Appearance - subepidermal linear pattern of Ab on immunofluorescence
    C. Clinical
    - pruritic tense fluid-containing blisters with eosinophils; do not pop easily (entire epidermal layer is lifted)
    - no mucosal involvement
    - Nikolsky sign negative
63
Q

[Skin pathology]
Blistering lesions - cause, appearance, clinical
3. Dermatitis herpetiformis
4. Erythema multiforme

A
  1. Dermatitis herpetiformis
    A. Cause - IgA anti-gliadin Ab cross-react with reticulin (anchoring fibrils) in basement membrane
    - associated with Celiac disease
    B. Appearance - granular IgA deposition at tips of dermal papillae on immunofluorescence - accumulation of neutrophils
    C. Clinical - groups of itchy papules and blisters (look like herpes vesicles) on extensor surfaces e.g. elbows
  2. Erythema multiforme
    A. Cause - cell-mediated immune response against antigens deposited in skin
    - associated with infection (HSV1), drugs (sulfa drugs, beta lactams, phenytoin)
    B. Appearance - multiple types of lesions; most characteristic is target lesions with central grey necrosis
    C. Clinical - in young adults
64
Q

[Skin pathology]
Blistering lesions - cause, appearance, clinical
5. Stevens-Johnson syndrome / Toxic epidermal necrolysis

A
  1. Stevens-Johnson syndrome / Toxic epidermal necrolysis

A. Cause - adverse drug reaction - sulfonamides, allopurinol, anti-epileptics (carbamazepine, phenytoin, lamotrigine), penicillin

  • infection in children (mycoplasma)
  • risk factors: HIV, HLA-A and HLA-B

B. Appearance - sloughing of skin at epidermal-dermal junction –> entire epidermis sloughs off
- targetoid skin lesions (like in erythema multiforme)

C. Clinical - bullae formation + necrosis + fever

  • 2 distinct mucous membranes involved (oral, ocular, genital)
  • SJS - <10% body surface area
  • SJS-TEN - 10-30%
  • TEN - > 30%
  • high mortality rate
65
Q

[Skin pathology]
Acute inflammation - cause, appearance, clinical
1. Urticaria
2. Eczema

A
  1. Urticaria
    A. Cause - Type 1 HSN (allergy) - Antigen binding to IgE on mast cell –> Degranulation
    B. Appearance - edema in dermis (epidermis normal)
    C. Clinical - red plaques (wheals) on trunk and extremities - transient
  2. Eczema / atopic dermatitis
    A. Cause - Type 1 HSN –> serum IgE
    *Type 4 HSN - contact dermatitis e.g. nickel reaction, poison ivy
    - associated with other atopic diseases (Asthma, food allergies)
    - antigen is transported by Langerhans cells to the lymph node –> T cells sensitized
    B. Appearance - spongiosis (edema in epidermis)
    C. Clinical - itchy eruptions of intraepidermal spongiotic vesicle on skin flexures
    - appears on face in infancy and then antecubital fossa (elbow pit)
    - persistent - acanthosis (diffuse epidermal hyperplasia), hyperkeratosis (stratum corneum - outermost layer of epidermis - thickens)
66
Q

[Skin pathology]
Acute inflammation - cause, appearance, clinical
3. Acne vulgaris
4. Rosacea

A
  1. Acne vulgaris
    A. Cause - increased keratin and sebum production (hormone sensitive) block pilosebaceous follicles –> form comedones (open = whitehead, closed = blackhead)
    - Propionibacterium acnes infection within follicle –> produce lipases that break down sebum and release inflammatory factors –> pustule formation (pimple)
    B. Appearance - pustules (pimples), nodules (scarred pimples), cysts
  2. Rosacea
    A. Cause - vascular hyperreactivity
    B. Appearance - red papules and pustules, looks like acne but no comedones; telangiectasias
    C. Clinical - frequent and prolonged flushing in response to external stimuli e.g. alcohol, heat
    - phymatous rosacea causes rhinophyma (bulbous deformation of nose)
    - in older individuals
67
Q

[Skin pathology]
Chronic inflammation - cause, appearance, clinical
1. Psoriasis

A
  1. Psoriasis

A. Cause - autoimmune - T cell (Th17) response with hyperproliferation of keratinocytes

  • HLA-Cw allele (same as psoriatic arthritis)
  • DDx is fungal infection

B. Appearance

  • parakeratosis –> hyperkeratosis with retention of nuclei in stratum corneum (outermost layer of epidermis consisting of dead cells)
  • Munro microabscesses - neutrophils in stratum corneum
  • acanthosis - epidermal hyperplasia –> due to decreased stratum granulosum and increased stratum spinosum
  • thin epidermis over dermal papillae –> positive Auspitz sign
  • dilated bv, lymphocytic infiltrate

C. Clinical - well-demarcated salmon-colored plaques with silvery scaling on knees and elbows

  • Auspitz sign - pinpoint bleeding spots from exposure of bv in dermal papillae when scales are scraped off
  • associated with nail pitting, psoriatic arthritis
68
Q 
[Skin pathology]
Chronic inflammation - cause, appearance, clinical
2. Lichen planus
3. Erythema nodosum 
4. Erythema migrans
5. Eythema marginatum
A
  1. Lichen planus
    A. Cause - associated with chronic hepatitis C
    B. Appearance
    - lymphocytic infiltrate at dermal-epidermal junction –> sawtooth rete ridges (epithelial projection into underlying connective tissue)
    - hypergranulosis - increased thickness of stratum granulosum (as opposed to psoriasis)
    C. Clinical - 6 P’s –> Pruritic, Purple, Polygonal, Planar, Papules, and Plaques
    - Wickham striae - visible white lines on oral mucosa
  2. Erythema nodosum -
    A. Cause - idiopathic but can be associated with coccidioidomycosis, histoplasmosis, TB, streptococcal infections, leprosy, inflammatory bowel disease, sarcoidosis
    B. Appearance - inflammation of subcutaneous fat
    C. Clinical - painful, inflammatory lesions on anterior shins
  3. Erythema migrans
    A. Cause - lyme disease Borrelia burgdorferi (stage 1)
    B. Appearance - large rash with bull’s eye
  4. Erythema marginatum
    A. Cause - acute rheumatic fever (E in JONES criteria)
    B. Appearance - red border, not itchy, on trunk
69
Q

[Skin pathology]
Skin disorders - cause, appearance, clinical
1. Verrucae
2. Molluscum contagiosum

A
  1. Verrucae = warts
    A. Cause - HPV 1-4, 6 and 11
    B. Appearance - acanthosis (epidermal hyperplasia)
    - hyperkeratosis
    - koilocytosis
    C. Clinical - flesh-colored papule with rough surface
    - HPV 1-4 - verruca vulgaris (common wart) on hands and feet
    - HPV 6 and 11 - condyloma acuminatum (anogenital wart) on genitals
  2. Molluscum contagiosum
    A. Cause - DNA pox virus
    B. Appearance - Molloscum bodies - pink cytoplasmic viral inclusions
    - acanthosis + hyperkeratosis
    C. Clinical - firm, pink dome-shaped papules with central umbilication
    - most commonly seen in children
    - sexually transmitted in adults, usually have one lesion (if multiple, probably immunosuppressed)
70
Q

[Skin pathology]
Skin disorders - cause, appearance, clinical
3. Herpes zoster
4. Acanthosis nigricans

A
  1. Herpes zoster = shingles
    A. Cause - Varicella zoster virus (VZV), reactivated from the dorsal root in older patients or immunocompromised
    B. Appearance - acantholysis
    - intraepidermal blisters
    - floating keratinocytes
    - multinucleated cells
    - Cowdry bodies = eosinophilic viral nuclear inclusion bodies (also seen in HSV)
    C. Clinical - painful “dew drop on rose” rash in dermatomal distribution, does not cross the midline (considered to be disseminated if it does)
  2. Acanthosis nigricans
    A. Cause - obesity, insulin resistance, paraneoplastic - associated with gastric cancer
    B. Appearance - hyperpigmented velvety plaques in axilla and on neck
71
Q

[SSTIs]
Describe the following SSTIs including epi, cause, clinical, and treatment
1. Impetigo - bullous vs non-bullous
2. Erysipelas

A
  1. Impetigo
    A. Epi - most common skin infection in children
    - highly communicable, increased in hot weather
    B. Cause - Staph aureus, beta hemolytic Group A strep (e.g. Strep pyogenes)
    C. Clinical
    i. Non-bullous - clusters of superficial non-follicular pustules –> rupture of pustules leads to erosions and dry, “honey crust”, painless
    - on face and extremities, lymphadenopathy
    ii. Bullous - on the trunk, much larger lesions; due to exfoliative toxin from Staph aureus
    D. Treatment - topical antibiotics
  2. Erysipelas
    A. Epi - in adults > 60
    B. Cause - Strep pyogenes
    C. Clinical - superficial, up to upper dermis + superficial lymphatics
    - raised, shiny plaque with well-defined demarcation between infected and normal skin
    - most commonly on lower limb, unilateral
    D. Treatment - oral antibiotics
72
Q

[SSTIs]
Describe the following SSTIs including epi, cause, clinical, and treatment
3. Cellulitis
4. Abscess

A
  1. Cellulitis
    A. Epi - in adults
    B. Cause - break in skin from trauma, insect bite; most commonly Strep pyogenes, less common is Staph aureus
    C. Clinical - acute, painful, spreading infection of deeper dermis and subcutaneous fat –> red, tender, swollen rash with fever
    - can have purulent wound even in absence of drainable abscess –> can lead to necrotizing fasciitis
    D. Treatment
    i. non-prurulent - (GABHS) cephalexin, dicloxacillin, clindamycin
    ii. prurulent - (MRSA) clindamycin, TMP-SMX, doxy or linezolid
  2. Abscess
    A. Epi
    B. Cause - Staph aureus
    C. Clinical - collection of pus from walled-off infection within deeper layers of skin; nodule with fluctuence and surrounding redness
    D. Treatment - incision and drainage, don’t need antibiotics
73
Q 
[SSTIs]
Describe the following SSTIs 
5. Necrotizing soft tissue infection 
A. Cause 
B. Clinical 
C. Types
  1. Scalded skin syndrome
A
  1. Necrotizing soft tissue infection (necrotizing fasciitis)
    A. Cause - bacterial toxins (Strep pyogenes, anaerobic “flesh eating” bacteria - Clostridium perfringens) damage endothelium –> increased permeability –> edema –> impairs capillary flow –> extensive small vessel thrombosis –> tissue ischemia and necrosis
    - involves any of the layers
    B. Clinical - pain out of proportion to physical findings
    - erythema, swelling with tenderness –> black eschar, crepitus (methane and C02 production), numbness, purple color
    C. Types
    Type I - polymicrobial, seen in obese, diabetics
    Type II - GABHS, seen in young healthy hosts, associated with blunt trauma
    Type III - Vibrio, exposure to sea water, risk factor is liver disease
  2. Staphylococcal Scalded skin syndrome
    A. Cause - Staph aureus exfoliative A and B toxins circulate in bloodstream, acts at desmogleins in stratum granulosum
    B. Clinical - seen in newborns (umbilical stump), infants, immunocompromised adults
    - diffuse sloughing of skin with red rash and fever –> significant skin loss
    - positive Nikolsky sign (similar to pemphigus vulgaris)
    - differentiated from TEN (also has massive sloughing) - but there the sloughing is at dermal-epidermal junction
74
Q 
[Calcium]
Hyperparathyroidism - describe including causes, plasma levels (PTH, Ca2+, P043-, ALP) and clinical presentation
1. Primary
2. Secondary
3. Tertiary
A

Hyperparathyroidism

  1. Primary
    A. Cause - parathyroid adenoma, MEN1, MEN2A
    B. Plasma levels - ↑ PTH, ↑ Ca2+, ↑ ALP, ↓ P043-, ↑ urine Ca2+ and P043-
    C. Clinical - “bones, stones, groans, psychiatric moans”
    - osteitis fibrosa cystica –> cystic spaces filled with brown fibrous tissue (osteoclasts + deposited hemosiderin) –> cortical bone loss
    - hypercalciuria –> renal stones
    - abdominal groans –> GI symptoms
    - psychiatric –> lethargy, memory loss, depression
  2. Secondary
    A. Cause - chronic kidney disease –> P043- retention –> hypocalcemia from deposition
    B. Plasma levels - ↓ Ca2+, ↑ P043-, ↑ PTH, ↑ ALP
    C. Clinical - renal osteodystrophy (↓ vitamin D) –> secondary hyperPTH –> bone resorption
  3. Tertiary
    A. Cause - refractory hyperparathyroidism from chronic kidney disease
    B. Plasma levels - ↑ PTH, ↑ Ca2+
75
Q 
[Calcium]
Hypoparathyroidism - describe including causes, plasma levels (PTH, Ca2+, P043-, ALP) and clinical presentation
1. Hypoparathyroidism
2. Pseudohypoparathyroidism type 1A
3. Pseudopseudohypoparathyroidism
A
  1. Hypoparathyroidism
    A. Cause - postsurgical, autoimmune, DiGeorge
    B. Plasma levels - ↓ PTH, ↓ Ca2+, ↑ P043-, ↓ Vit D
    C. Clinical - hypocalcemia –> Chvostek sign (tap cheek to contract facial muscles), Trousseau sign (occlude brachial artery with BP cuff for carpal spasm)
  2. Pseudohypoparathyroidism type 1A (serum levels show hypoPTH but PTH is actually increased)
    A. Cause - AD Albright hereditary osteodystrophy - Defective Gs alpha (inherited from mother)–> end-organ resistance to PTH
    B. Plasma levels - ↑ PTH, ↓ Ca2+, ↑ P043-
    C. Clinical - short stature, shortened 4th/5th digits
  3. Pseudopseudohypoparathyroidism
    A. Cause - defective Gs alpha protein subunit inherited from father
    B. Plasma levels - normal PTH, Ca2+, P043-
    C. Clinical - same as Albright (short stature, shortened 4th/5th digits)
76
Q 
[Calcium]
Hypocalcemia
1. Clinical presentation
2. Vitamin D deficiency
3. Rickets/Osteomalacia
A

Hypocalcemia

  1. Clinical presentation - neuromuscular irritability
    - muscle spasms/cramps –> - Chvostek sign (facial nerve), Troussea sign (tetany of hand)
    - mood changes, convulsions
    - prolonged QT –> torsades / ventricular arrhythmias
    - fragile bones, erosions
    - paresthesias - numbness and tingling
  2. Vitamin D deficiency
    - deficient supply (darker skin, not in sunlight) –> rickets/osteomalacia, osteoporosis
    - deficient activation e.g. renal failure (Secondary hyperparathyroidism)
    - screen via 25(OH)D - calcidiol (calcitriol 1,25(OH)2D3 is active form and has shorter half-life)

3A. Rickets - low vitamin D in children –> abnormal mineralization of cartilage during endochondral bone formation

  • genu varum (bow-legged)
  • rachitic rosary
  • pigeon-breast deformity (ribs bend inwards)
  • frontal bossing

B. Osteomalacia - low vitamin D in adults –> defective mineralization of osteoid –> weak bone
- ↑ ALP, ↑ PTH, ↓ Ca2+, ↓ P043-, ↓ 25(OH)D3, ↓ urine Ca2+

77
Q 
[Calcium]
Hypercalcemia
1. Clinical presentation
2. Common causes - inpatient vs outpatient
3. Familial hypocalciuric hypercalcemia
4. Vitamin D excess
A

Hypercalcemia
1. Clinical presentation - bones (bone pain), stones (kidney), groans (abdominal pain), psychiatric moans

  1. Causes
    A. Outpatient - parathyroid adenoma (primary hyperPTH)
    B. Inpatient - PTHrP (humoral hypercalcemia of malignancy)
    - PTHrP activate osteoblasts –> activate osteoclasts –> osteoclasts release TGFbeta which stimulates tumor cell growth + bone resorption (does not activate Vitamin D)
    - ↑ Ca2+, ↓ PTH, ↓ P043-, ↑ urine Ca2+ and P043-
  2. Familial hypocalciuric hypercalcemia
    A. Cause - AD inactivating mutation in CaSR (G-protein coupled receptor) in parathyroid, kidneys
    B. Plasma levels - ↑ Ca2+, mildly ↑ PTH, ↓ urinary calcium (primary hyperPTH has high urine Ca2+)
    C. Clinical - asymptomatic; higher than normal Ca2+ required to suppress PTH
    - cinacalcet increases sensitivity to Ca2+
  3. Vitamin D excess - unregulated 1alpha hydroxylase activity independent of PTH
    - due to sarcoidosis (macrophages) and lymphoma (lymphocytes) which express the enzyme
    - ↑ Vit D, ↓ PTH
78
Q 
[Calcium]
Pharmacology - MOA, indications, adverse effects
1. Bisphosphonates
2. Raloxifene
3. Denosumab
4. Teriparatide
5. Meds for secondary hyperPTH
A. Cincalcet
B. Sevelamer
C. Vit D
A
  1. Bisphosphonates “-dronate”
    A. MOA - bind to hydroxyapatite at remodeling sites –> ingested by osteoclasts –> induce osteoclast apoptosis + inhibit devlpt of osteoclast precursors
    B. Indications - first line for osteoporosis, hypercalcemia of malignancy, Paget disease
    C. Adverse effects - upper GI (acid reflux), osteonecrosis of jaw, esophagitis
  2. Raloxifene (SERM)
    A. MOA - agonist in bone (increase OPG –> inhibits osteoclast differentiation) and antagonist at estrogen receptors in breast and tissue
    B. Indications - postmenopausal osteoporosis, second-line for osteoporosis
  3. Denosumab - v expensive
    A. MOA - monoclonal Ab, acts as OPG and binds to RANKL –> inhibits osteoclast stimulation
    B. Indications - osteoporosis, esp postmenopausal
  4. Teriparatide - recombinant PTH
    A. MOA - stimulates maturation of osteoblasts and bone formation
    B. Indications - severe osteoporosis
    C. Adverse effects - contraindicated with pre-existing hypercalcemia, Paget’s disease
  5. Meds for secondary hyperPTH (due to renal failure)
    A. cinacalcet - ↑ CaSR activity –> inhibits PTH
    B. Sevelamer - phosphate binder –> decreases phosphate absorption in gut
    C. Vitamin D preparations - cholecalciferol (D3), ergocalciferol (D2), calcitriol (1,25(OH)2D3) –> directly inhibit PTH secretion
79
Q 
[Soft Tissue Injury]
Differentiate: 
1. Ligament, tendon
2. Strain, sprain
3. Soft tissue contusion
4. Rotator cuff muscles + injury
5. Adhesive capsulitis
A

1A. Ligament - short band of fibrous connective tissue that connects bone to bone
B. Tendon - cord of fibrous connective tissue that connects muscle to bone

2A. Strain - injury to muscle and/or tendon
B. Sprain - injury to ligament

  1. Soft tissue contusion - high velocity compression injury to muscle –> muscle tissue crushed –> localized hemorrhage –> reparative inflammatory response
  2. Rotator cuff muscles = SITS (C5-C6)
    - supraspinatus - abducts arm; test via empty/full can test
    - infraspinatus - external rotation
    - teres minor - external rotation + adduction
    - subscapularis - internal rotation
    - can have impingement, strain (young athletes), tear (older patients)
  3. Adhesive capsulitis - “frozen shoulder”
    - scarring of shoulder capsule, painful on passive ROM

M2 (11 decks)

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