Musculoskeletal Flashcards
Fat redistribution (drug reaction)
Protease inhibitors
Glucocorticoids
Gingival hyperplasia (drug reaction)
Phenytoin
Ca channel blockers
Cyclosporine
Hyperuricemia (gout) - drug reaction
Pyrazinamide Thiazides Furosemide Niacin Cyclosporine
Myopathy (drug reaction)
Fibrates Niacin Colchicine Hydroxychloroquine Interferon alpha Penicillamine Statins Glucocorticoids
Osteoporosis (drug reaction)
Croticosteroids
Heparin
Photosensitivity (drug reaction)
Sulfonamides
Amiodarone
Tetracyclines
5-FU
Rash (SJS) - drug reaction
Anti-epileptic drugs (esp lamotrigine)
Allopurinol
Sulfa drugs
Penicillin
SLE-like syndrome (drug reaction)
Sulfa drugs Hydralazine Isoniazid Procainamide Phenytoin Etanercept
Teeth discoloration (drug reaction)
Tetracyclines
Tendonitis, tendon rupture, and cartilage damage (drug reaction)
Fluoroquinolones
Anterior drawer sign
With patient supine, bending knee at 90 degree angle, increased anterior gliding of tibia due to ACL injury
Posterior drawer sign
With patient supine, bending knee at 90 degree angle, increased posterior gliding of tibia due to PCL injury
Abnormal passive abduction
With patient supine and knee either extended or at about 30 degree angle, lateral (valgus) force leads to medial space widening of tibia - MCL injury
Abnormal passive adduction
With patient supine and knee either extended or at about 30 degree angle. medial (varus) force leads to lateral space widening of tibia - LCL injury
McMurray Test
With the patient supine and knee internally and externally rotated during rotated during range of motion:
Pain, “popping” on external rotation - medial meniscus tear
Pain, “popping” on internal rotation - lateral meniscus tear
Unhappy Triad
Common injury in contact sports due to lateral force applied to a planted leg
Classically, consists of damage to ACL, MCL and medial meniscus (attached to MCL); however, lateral meniscus injury is more common.
Presents with acute knee pain and signs of joint injury/instability
Prepatellar bursitis
“Housemaid’s knee”
Can be caused by repeated trauma or pressure from extensive kneeling
Baker Cyst
Popliteal fluid collection commonly related to chronic joint disease
Rotator Cuff muscles
Shoulder muscles that form the cuff:
Supraspinatus (suprascapular nerve) - abducts arm initially (before the action of the deltoid); most common rotator cuff injury, assessed by “empty/full can” test
Infraspinatus (suprascapular nerve too) - laterally rotates arm; pitching injury
Teres minor (axillary nerve) - adducts and laterally rotates arm
Subscapularis (upper and lower subscapular nerves) - medially rotates and adducts arm
Innervated by C5-C6
Medial epicondylitis
Golfer’s elbow
Repetitive flexion (forehand shots) or idiopathic leading to pain near medial epicondyle
Lateral epicondylitis
Tennis elbow
Repetitive extension (backhand shot) or idiopathic leading to pan near lateral epicondyle
Wrist bones
So Long To Pinky, Here Comes The Thumb
Scaphoid Lunate Triquetrum Pisiform Hamate Capitate Trapezoid Trapezium
Scaphoid (palpated in anatomic snuff box) is the most commonly fractured carpal bone and is prone to avascular necrosis owing to retrograde blood supply
Dislocation of lunate may cause acute carpal tunnel syndrome
A fall on an outstretched hand that damages the hook of the hamate can cause ulnar nerve injury
Carpal tunnel syndrome
Entrapment of median nerve in carpal tunnel; nerve compression leads to paresthesia, pain, and numbness in distribution of median nerve. Associated with pregnancy, RA, hypothyroidism; may be associated with repetitive use
Guyon canal syndrome
Compression of ulnar nerve at wrist or hand. Classically seen in cyclists due to pressure from handlebars
Axillary nerve
C5-C6
Injury causes: Fractured surgical neck of humerus; anterior dislocation of humerus
Presents:
Flattened deltoid
Loss of arm abduction at shoulder (more than 15 degrees)
Loss of sensation over deltoid muscle and lateral arm
Musculocutaneous nerve
C5-C7
Injury from: Upper trunk compression
Presents:
Loss of forearm flexion and supination
Loss of sensation over lateral forearm
Median nerve
C5-T1
Injury from: Supracondylar fracture of humerus (proximal lesion); carpal tunnel syndrome and wrist laceration (distal lesion)
Presents:
Ape Hand and Pope’s Blessing
Loss of wrist flexion, flexion of lateral fingers, thumb opposition, lumbricals of 2nd and 3rd digits
Loss of sensation over thenar eminence and dorsal and palmar aspects of lateral 3 1/2 fingers with proximal lesion
Tinel sign (tingling on percussion) in carpal tunnel syndrome
Radial nerve
C5-T1
Injury from: Midshaft fracture of humerus; compression of axilla (due to crutches or sleeping with arm over chair) - “Saturday night palsy”
Presents:
Wrist Drop: loss of elbow, wrist and finger extension
Lower grip strength (wrist extension necessary for maximal action of flexors)
Loss of sensation over posterior arm/forearm and dorsal hand
Ulnar nerve
C8-T1
Injury from: Fracture of medial epicondyle of humerus “funny bone” (proximal lesion); fractured hook of hamate (distal lesion)
Presents:
Ulnar claw on digit extension
Radial deviation of wrist upon flexion (proximal lesion)
Loss of wrist flexion, flexion of medial fingers, abduction and adduction of fingers (interossei), actions of medial 2 lumbrical muscles
Loss of sensation over medial 1 1/2 fingers including hypothenar eminence
Recurrent branch of median nerve
C5-T1
Injury from: Superficial laceration of palm
Presents:
Ape Hand
Loss of thenar muscle group: opposition, abduction, and flexion of thumb
No loss of sensation
Erb Palsy (Waiter’s Tip)
Injury = traction or tear of upper trunk: C5-C6 roots
Causes = Infants - lateral traction on neck during delivery. Adults - trauma
Muscle deficit =
1) Deltoid, supraspinatus - Abduction (arm hangs by side)
2) Infraspinatus - Lateral rotation (arm medially rotated)
3) Biceps brachii - Flexion, supination (arm extended and pronated)
Klumpke Palsy
Injury = Traction or tear of lower trunk: C8-T1 root
Causes = Infants - upward force on arm during delivery
Adults - trauma (grabbing a tree branch to break a fall)
Muscle deficit = Intrinsic hand muscles: Lumbricals, interossei, thenar, hypothenar - Total claw hand: Lumbricals normally flex MCP joints and extend DIP and PIP joints
Thoracic outlet syndrome
Injury = compression of lower trunk and subclavian vessels
Causes = Cervical rib, Pancoast tumor
Muscle deficit = same as Klumpke - Atrophy of intrinsic hand muscles; ischemia, pain, and edema due to vascular compression
Winged Scapula
Injury = Lesion of long thoracic nerve
Causes = axillary node dissection after mastectomy, stab wounds
Muscle deficit = Serratus anterior - inability to anchor scapula to thoracic cage leading to inability to abduct arm above horizontal position
Distortions of the hand
At rest, a balance exists between the extrinsic flexors and extensors of the hand, as well as the intrinsic muscles of the hand - particularly the lumbrical muscles (flexion of MCP, extension of DIP and PIP joints)
Clawing - seen best with distal lesions of median or ulnar nerves. Remaining extrinsic flexors of the digits exaggerate the loss of the lumbricals - fingers extend at MCP, flex at DIP and PIP
Deficits less pronounced in proximal lesions; deficits present during voluntary flexion of digits
Hand muscles
Thenar (median) - Opponens pollicis; Abductor pollicis brevis, Flexor pollicis brevis, superficial head (deep head by ulnar nerve)
Hypothenar (ulnar) - Opponens digiti minimi, Abductor digiti minimi, Flexor digiti minimi brevis
OAF for both (Oppose, Abduct, Flex)
Dorsal interossei - abduct the fingers (DAB)
Palmar interossei - adduct the finers (PAD)
Lumbricals - flex at the MCP joint, extend PIP and DIP joints
Obturator nerve
L2-L4
Damage: Pelvic surgery
Presents:
Lower thigh sensation (medial) and lower adduction
Femoral nerve
L2-L4
Damage: Pelvic fracture
Presents:
Low thigh flexion and leg extension
Common peroneal nerve
L4-S2
Damage: Trauma or compression of lateral aspect of leg, fibular neck fracture
Presents:
Foot drop - inverted and plantarflexed at rest, loss of eversion and dorsiflexion. “Steppage Gait” Loss of sensation on dorsum of foot
Tibial nerve
L4-S3
Damage: Knee trauma, Baker Cyst (proximal lesion)
Tarsal tunnel syndrome (distal lesion)
Presents:
Inability to curl toes and loss of sensation on sole of foot. In prox lesions, foot everted at rest with loss of inversion and plantarflexion
Superior gluteal nerve
L4-S1
Damage: Iatrogenic injury during intramuscular injection to upper medial gluteal region
Presents:
Trendelenburg sign/gait - pelvis tilts bc weight-bearing leg cannot maintain alignment of pelvis through hip abduction (superior nerve supplies medius and minimus)
lesion is contralateral to the side of the hip that drops, ipsilateral to extremity on which the patient stands
Inferior gluteal nerve
L5-S2
Damage: Posterior hip dislocation
Presents:
trouble climbing stairs, rising from seated position. Loss of hip extension (inferior nerve - maximum)
Sciatic and pudendal nerves
Sciatic nerve (L4-S3) innervates posterior thigh, splits into common peroneal and tibial nerves
Pudendal nerve (S2-S4) innervates perineum. Can be blocked with local anesthetic during childbirth using the ischial spine as a landmark for injection
Signs of lumbrosacral radiculopathy
Paresthesias and weakness in distribution of specific lumbar or sacral spinal nerves.
Often due to IVdisc herniation in which the nerve association with the inferior vertebral body is impinged (herniation of L3-L4 disc affects the L4 spinal nerve)
IV discs generally herniate posterolaterally, due to the thin posterior longitudinal ligament and thicker anterior longitudinal ligament along the midline of the vertebral bodies
L3-L4 disc level - weakness of knee extension, reduced patellar reflex
L4-L5 disc level - Weakness of dorsiflexion, difficulty in heel-walking
L5-S1 disc level - Weakness of plantarflexion, difficulty in toe-walking, reduced Achilles reflex
Neurovascular pairings
Nerves and arteries are frequently named together by the bones/regions with which they are associated. There are exceptions though:
1) Axilla/lateral thorax = Long thoracic N/ Lateral thoracic A
2) Surgical neck of humerus = Axillary N/ Posterior circumflex A
3) Midshaft of humerus = Radial N/ Deep brachial A
4) Distal humerus/cubital fossa = Median N/ Brachial A
5) Popliteal fossa = Tibial N/ Popliteal A
6) Posterior to medial malleolus = Tibial N/ Posterior Tibial A
Muscle conduction to contraction (7 steps)
1) Action potential depolarization opens presynaptic voltage-gated Ca channels, inducing nt release
2) Postsynaptic ligand binding leads to muscle cell depolarization in the motor end plate
3) Depolarization travels along muscle cell and down T-tubule
4) Depolarization of the voltage sensitive dihydropyridine receptor, mechanically couple to the ryanodine receptor on the sarcoplasmic reticulum, induces a conformational change, causing Ca release from SR
5) Released Ca binds to troponin C, causing a conformational change that moves tropomyosin out of the myosin-binding groove on actin filaments
6) Myosin releases bound ADP and inorganic PO4 leading to displacement of myosin on the actin filament (power stroke). Contraction results in shortening of H and I bands and between Z lines (HIZ shrinkage), but the A band remains the same length (A is Always the same)
7) Binding of a new ATP molecule causes detachment of myosin head from actin filament. Hydrolysis of bound ATP to ADP, myosin head adapts high-energy position (“cocked”) for the next contraction cycle
T tubules (extensions of plasma membrane juxtaposed with terminal cisternae) are part of the sarcoplasmic reticulum
Skeletal muscle, 1 T tubule + 2 terminal cisternae = triad
Cardiac muscle, 1 T tubule + 1 terminal cisternae = diad
Types of muscle fibers
Type 1 - slow twitch; red fibers resulting from increased mitochondria and myoglobin concentration (Increased oxidative phosphorylation) - sustained contraction
Type 2 - fast twitch; white fibers resulting from lower mitochondria and myoglobin concentrations (increased anaerobic glycolysis); weight training results in hypertrophy of fast-twitch muscle fibers
Endochondral ossification
Bones of axial and appendicular skeleton and base of skull. Cartilaginous model of bone is first made by chondrocytes.
Osteoclasts and osteoblasts later replace with woven bone and then remodel to lamellar bone. In adults, woven bone occurs after fractures and in Paget Disease
Membranous ossification
Bones of calvarium and facial bones. Woven bone formed directly without cartilage. Later remodeled to lamellar bone.
Osteoblasts
Build bone by secreting collagen and catalyzing mineralization. Differentiates from mesenchymal stem cells in periosteum
Osteoclasts
Multinucleated cells that dissolve bone by secreting acid and collagenases. Differentiate from monocytes, macrophages
Parathyroid hormone
At low, intermittent levels, exerts anabolic effects (building bone) on osteoblasts and osteoclasts (indirect)
Chronically elevated PTH levels (primary hyperparathyroidism) cause catabolic effects (osteitis fibrosa cystica)
Estrogen
Estrogen inhibits apoptosis in bone-forming osteoblasts and induces apoptosis in bone-resorbing osteoclasts.
Estrogen deficiency (surgical or postmenopausal), excess cycles of remodeling, and bone resorption lead to osteoporosis.
Achondroplasia
Failure of longitudinal bone growth (endochondral ossification) leads to short limbs.
Membranous ossification is not affects - large head relative to limbs.
Constitutive activation of fibroblast growth factor receptor (FGFR3) actually inhibits chondrocyte proliferation.
> 85% of mutations occur sporadically
Autosomal dominant with full penetrance (homozygosity is lethal)
Most common cause of dwarfism
Primary Osteoporosis
Trabecular (spongy) bone loses mass and interconnections despite normal bone mineralization and lab values (serum Ca and PO4)
Diagnoses by a bone mineral density test (DEXA) with a T score less than or equal to -2.5
Can be caused by long-term exogenous steroid use, anticonvulsants, anticoagulants, thyroid replacement therapy
Can lead to vertebral compression fractures** - acute back pain, loss of height, kyphosis. Also can present with fractures of femoral neck, distal radius (Colles fracture)
1) Type 1 (post-menopausal) - increased bone resorption due to lower estrogen levels
2) Type 2 (senile) - Affects men and women > 70 years old.
Prophylaxis: Regular weight-bearing exercise and adequate Ca and Vitamin D intake throughout adulthood
Tx: Bisphosphonates, PTH analogs, SERMS, rarely calcitonin; denosumab (monoclonal antibody against RANKL)
Osteoporosis (Marble bone disease)
Failure of normal bone resorption due to defective osteoclasts leads to thickened, dense bones that are prone to fracture. Bone fills marrow space leading to pancytopenia, extramedullary hematopoiesis.
Mutations (carbonic anhydrase II) impair ability of osteoclast to generate acidic environment necessary for bone resorption. XR shows bone-in-bone appearance
Can result in cranial nerve impingement and palsies as a result of narrowed foramina
Bone marrow transplant is potentially curative as osteoclasts are derived from monocytes
Osteomalacia/Rickets
Vitamin D deficiency leads to osteomalacia in adults; rickets in children
Due to defective mineralization/calcification of osteoid we see soft bones that bow out
Low vitamin D leads to low serum Ca leading to high PTH secretion causing low serum PO4
Hyperactivity of osteoblasts leads to high ALP (osteoblasts require alkaline environment)
Paget Disease of bone (Osteitis deformans)
Common, localized disorder of bone remodeling caused by increases in both osteoblastic and osteoclastic activity
Serum Ca, phosphorous, and PTH levels are normal
Increased ALP
Mosaic pattern of woven and lamellar bone
Long bone chalk-stick fractures
Increased blood flow from increased arteriovenous shunts may cause high-output heart failure. Higher risk of osteogenic sarcoma
hat size can be increased; hearing loss is common due to auditory foramen narrowing
Stages:
1) Lytic - osteoclasts
2) Mixed - osteoclasts + osteoblasts
3) Sclerotic - osteoblasts
4) Quiescent - minimal osteoclast/osteoblast activity
Osteonecrosis (avascular necrosis)
Infarction of bone and marrow, usually very painful. Most common site is femoral head (due to insufficiency of medial circumflex femoral artery)
Causes include ASEPTIC
A = Alcoholism
S = Sickle Cell Disease, Storage
E = Exogenous/Endogenous corticosteroids
P = Pancreatitis
T = Trauma
I = Idiopathic (Legg-Calve-Perthes disease)
C = Caisson ("the bends")
Giant cell tumor
benign primary bone tumor
20-40 years old. Epiphyseal end of long bones. “Osteoclastoma”
Locally aggressive benign tumor often around knee
“Soap bubble” appearance on XR
Multinucleated giant cell
Osteochondroma
benign primary bone tumor
Most common benign tumor (an exostosis of the bone)
Males
Osteosarcoma (Osteogenic sarcoma)
Malignant primary bone tumor
2nd most common primary malignant bone tumor (after multiple myeloma)
Bimodal distribution - 10-20 years old (primary), > 65 (secondary)
Predisposing factors: Paget disease of bone, bone infarcts, radiation, familial retinoblastoma, Li-Fraumeni syndrome (germline p53 mutation)
Metaphysis of long bones, often around knee
Codman triangle (from elevation of periosteum) or sunburst pattern on XR
Aggressive. Treat with surgical en block resection (with limb salvage) and chemotherapy
Ewing sarcoma
Malignant primary bone tumor
Boys
Osteoarthritis
1) Etiology: Mechanical - joint wear and tear destroys articular cartilage
2) Joint findings: Subchondral cysts, sclerosis, osteophytes (bone spurs), eburnation (polished, ivory-like appearance of bone), synovitis, Heberden nodes (DIP), Bouchard nodes (PIP). NO MCP INVOLVEMENT
3) Predisposing factors: Age, obesity, joint trauma
4) Classic presentation: Pain in weight-bearing joints after use (at the end of the day), improving with rest. Knee cartilage loss begins medially (“bowlegged”). Noninflammatory. No systemic symptoms.
5) Treatment: Acetaminophen, NSAIDs, intra-articular glucocorticoids
Rheumatoid arthritis
1) Etiology: Autoimmune - inflammatory destruction of synovial joints. Mediated by cytokines and type 3 and type 4 hypersensitivity reactions
2) Joint findings: Pannus (inflammatory granulation tissue) formation in joints (MCP, PIP), subcutaneous rheumatoid nodules (fibrinoid necrosis), ulnar deviation of fingers, subluxation. Rare swan neck and boutonniere deformities. Rare DIP involvement.
3) Predisposing factors: Females > Males. 80% have (+) RF (anti-IgG antibody); anti-cyclic citrullinated peptide antibody is more specific. Strong association with HLA-DR4
4) Classic presentation: Morning stiffness lasting more than 30 minutes and improving with use, symmetric joint involvement, systemic symptoms (fever, fatigue, weight loss, pleuritis, pericarditis)
5) Treatment: NSAIDs, glucocorticoids, disease-modifying agents (methotrexate, sulfasalazine), biologics (TNF-a inhibitors)
Sjogren Syndrome
Autoimmune disorder characterized by destruction of exocrine glands (especially lacrimal and salivary) by lymphocytic infiltrates. Predominantly affects females 40-60 years old.
Findings:
Inflammatory joint pain
Xeropthalmia (lower tear production and subsequent corneal damage)
Xerostomia (lower saliva production)
Presence of antinuclear antibodies: SS-A (anti-Ro) and/or SS-B (anti-La)
Bilateral parotid enlargement
A common primary disorder or a secondary syndrome associated with other autoimmune disorders (RA)
Complications: dental carries; mucosa-associated lymphoid tissue (MALT) lymphoma (may present as parotid enlargement)
Gout findings
Acute inflammatory monoarthritis caused by precipitation of monosodium urate crystals in joints. More common in males. Associated with hyperuricemia, which can be caused by:
1) Underexcretion of uric acid (90% of patients) - largely idiopathic; can be exacerbated by certain medications (thiazide diuretics)
2) Overproduction of uric acid (10%) - Lesch-Nyhan Syndrome, PRPP excess, increased cell turnover (tumor lysis syndrome), von Gierke Disease
Crystals are needle shaped and (-) birefringent under polarized light (yellow under parallel light, blue under perpendicular light)
Gout symptoms and Tx
Asymmetric joint distribution. Joint is swollen, red, and painful. Classic manifestation is painful MTP joint of big toe (podagra). Tophus formation (often on external ear, olecranon bursa, or Achilles tendon). Acute attack tends to occur after a large meal or alcohol consumption (alcohol metabolites compete for same excretion sites in kidney as uric acid leading to decreased uric acid secretion and subsequent buildup in blood)
Tx
Acute: NSAIDs (indomethacin), glucocorticoids, colchicine
Chronic (preventive): xanthine oxidase inhibitors (allopurinol, febuxostat)
Pseudogout
Presents with pain and effusion in a joint, caused by deposition of calcium pyrophosphate crystals within the joint space (chondrocalcinosis on XR). Forms basophilic, rhomboid crystals that are weakly birefringent under polarized light.
Usually affects large joints (classically the knee). Older than 50 years old; both sexes affected equally.
Diseases associated with pseudogout include hemochromatosis, hyperparathyroidism, osteoarthritis.
Treatment includes NSAIDs for sudden, severe attacks; glucocorticoids; colchicine for prophylaxis
Gout - crystals are yellow when parallel to the light
Pseudogout - crystals are blue when parallel to the light
Infectious arthritis
Staph aureus
Streptococcus
N. gonorrhoeae
Gonococcal arthritis is an STD that presents as a migratory arthritis with an asymmetric pattern. Affected joint is swollen, red, and painful. STD = Synovitis (knee), Tenosynovitis (hand) and Dermatitis (pustules)
Seronegative spondyloarthropathies
Arthritis without RF (no anti-IgG antibody). Strong association with HLA-B27 (gene that encodes for MHC class 1). Occurs more often in males.
PAIR
1) P = Psoriatic arthritis - joint pain and stiffness associated with psoriasis. Asymmetric and patchy involvement. Dactylitis (sausage fingers), “pencil in cup” deformity on XR.
Seen in fewer than 1/3 of patients with psoriasis
2) A = Ankylosing Spondylitis - Chronic inflammatory disease of spine and sacroiliac joints leading to ankylosis (stiff spine due to fusion of joints), uveitis, aortic regurgitation
Bamboo spine (vertebral fusion)
3) I = IBD - Crohn and UC are often accompanied by ankylosing spondylitis or peripheral arthritis
4) R = Reactive arthritis (Reiter Syndrome) - Classic triad - Conjunctivitis and anterior uveitis, Urethritis, Arthritis
Can’t see, can’t pee, can’t climb a tree
Post-GI (Shigella, Salmonella, Yersinia, Campylobacter) or Chlamydia infections.
Systemic lupus erythematosus - symptoms
Classic presentation: rash, joint pain, and fever, most commonly in a female of reproductive age and African descent.
Libman-Sacks endocarditis - nonbacterial, wart-like vegetations on both sides of valve
Lupus nephritis (type 3 hypersensitivity reaction)
- Nephritic = diffuse proliferative glomerulonephritis
- Nephrotic = membranous glomerulonephritis
RASH OR PAIN R = Rash (malar or discoid) A = Arthritis S = Soft tissue/serositis H = Hematologic disorders (cytopenias)
O = Oral/nasopharyngeal ulcers R = Renal disease, Raynaud phenomenon
P = Photosensitivity, Positive VDRL/RPR A = Antinuclear antibodies I = Immunosuppressants N = Neurologic disorders (seizures, psychosis)
Common causes of death in SLE:
Cardiovascular disease
Infections
Renal disease
SLE - findings and tx
Findings: Antinuclear antibodies (ANA) - sensitive, not specific
Anti-dsDNA antibodies - specific, poor prognosis (renal disease)
Anti-Smith antibodies - specific, not prognostic (directed against snRNPs)
Antihistone antibodies - sensitive for drug-induced lupus
Reduced C3, C4 and CH50 due to immune complex formation
Treatment:
NSAIDs, steroids, immunosuppressants, hydroxychloroquine
Antiphospholipid syndrome
Primary or secondary autoimmune disorder (most commonly in SLE)
Diagnose based on clinical criteria including history of thrombosis (arterial or venous) or spontaneous abortion along with laboratory findings of lupus anticoagulant, anticardiolipin, anti-B2 glycoprotein antibodies
Treat with systemic anticoagulation
Anticardiolipin antibodies and lupus anticoagulant can cause false-positive VDRL and prolonged PTT
Sarcoidosis
Characterized by immune-mediated, widespread noncaseating granulomas, elevated serum ACE levels, and elevated CD4+/CD8+ ratio.
Common in black females. Often asymptomatic except for enlarged lymph nodes. Findings on CXR of bilateral adenopathy and coarse reticular opacities; CT of the chest better demonstrates the extensive hilar and mediastinal adenopathy
Associated with restrictive lung disease (interstitial fibrosis), erythema nodosum, lupus pernio, Bell palsy, epithelioid granulomas containing microscoping Schaumann and asteroid bodies, uveitis, hypercalcemia (due to increased 1a-hydroxylase-mediated vitamin D activation in macrophages)
Tx = steroids
Polymyalgia rheumatica
Pain and stiffness in shoulders and hips, often with fever, malaise, weight loss
Does not cause muscular weakness. More common in women older than 50; associated with temporal (giant cell) arteritis
Findings = increased ESR, Increased CRP, normal CK
Tx = Rapid response to low-dose corticosteroids
Fibromyalgia
Most commonly seen in females 20-50 years old. Chronic, widespread musculoskeletal pain associated with stiffness, paresthesias, poor sleep, fatigue. Treat with regular exercise, antidepressants (TCAs, SNRIs), anticonvulsants
Polymyositis/Dermatomyositis
Increased CK, (+) ANA, (+) anti-Jo-1, (+) anti-SRP, (+) anti-Mi-2 antibodies.
Tx = steroids followed by long-term immunosuppressant therapy (methotrexate)
1) Polymyositis - Progressive symmetric proximal muscle weakness, characterized by endomysial inflammation with CD8+ T Cells. Most often involves shoulders
2) Dermatomyositis - Similar to polymyositis, but also involves malar rash (like SLE), Gottron papules, heliotrope (erythematous periorbital) rash, “shawl and face” rash, “mechanic’s hands,” increased risk of occult malignancy. Perimysial inflammation and atrophy with CD4+ T cells
Neuromuscular junction diseases
1) Myasthenia Gravis
Most common NMJ disorder
Autoantibodies to postsynaptic ACh receptor
Ptosis, diplopia, weakness. Worsens with muscle use.
Associated with Thymoma, thymic hyperplasia
AChE inhibitors reverse symptoms
2) Lambert-Eaton myasthenic syndrome
Uncommon
Autoantibodies to presynaptic Ca channel leads to lower ACh release
Proximal muscle weakness, autonomic symptoms (dry mouth, impotence). Improves with muscle use.
Associated with small cell lung cancer
AChE inhibitors have minimal effect
Myositis ossificans
Metaplasia of skeletal muscle into bone following muscular trauma. Most often seen in upper or lower extremity. May present as suspicious “mass” at site of known trauma or as incidental finding on radiography
Scleroderma (systemic sclerosis)
Triad of autoimmunity, noninflammatory vasculopathy, and collagen deposition with fibrosis.
Commonly seen sclerosis of skin, manifesting as puffy, taut skin without wrinkles, fingertip pitting. Also sclerosis of renal, pulmonary (most common cause of death), cardiovascular, GI systems. 75% female. 2 major types
1) Diffuse scleroderma - widespread skin involvement, rapid progression, early visceral involvement. Associated with anti-Scl 70 antibody (anti-DNA topoisomerase I antibody)
2) Limited scleroderma - limited skin involvement confined to fingers and face. Also with CREST involvement Calcinosis Raynaud Esophageal dysmotility Sclerodactyly Telangiectasia
More benign clinical course. Associated with anti-centromere antibody.
Epidermis layers
3 layers of skin = epidermis, dermis, and subcutaneous fat (subcutis, hypodermis)
From surface to base: Stratum Corneum (keratin) Lucidum Granulosum Spinosum (desmosomes) Basale (stem cell site)
Epithelial cell junctions
Tight junctions (zona occludens) - prevents paracellular movement of solutes; composed of claudins and occludins
Adherens junction (zona adherens) - below tight junction, forms “belt” connecting actin cytoskeltons of adjacent cells with Cadherins (ca dependent adhesion proteins). Loss of E-cadherin promotes metastasis
Desmosome (macula adherens) - structural support via keratin interactions. Autoantibodies lead to pemphigus vulgaris
Gap junction - channel proteins called connexons permit electrical and chemical communication between cells
Integrins - membrane proteins that maintain integrity of basolateral membrane by binding to collagen and laminin in basement membrane
Hemidesmosome - connects keratin in basal cells to underlying basement membrane. Autoantibodies leads to bullous pemphigoid (hemidesmosomes are down “Bullo”w)
Dermatologic macroscopic terms (morphology)
1) Macule - flat lesion with well-circumscribed change in skin color 1 cm (large birthmark - congenital nevus)
3) Papule - elevated solid skin lesion 1 cm (Psoriasis)
5) Vesicle - small fluid-containing blister 1 cm (Bullous pemphigoid)
7) Pustule - vesicle containing pus (pustular psoriasis)
8) Wheal - Transient smooth papule or plaque (Hives - urticaria)
9) Scale - Flaking off of stratum corneum (Eczema, psoriasis, SCC)
10) Crust - Dry exudate (impetigo)
Derm microscopic terms
1) Hyperkeratosis - increased thickness of stratum corneum (Psoriasis, calluses)
2) Parakeratosis - Hyperkeratosis with retention of nuclei in stratum corneum (Psoriasis)
3) Spongiosis - Epidermal accumulation of edematous fluid in intercellular spaces (Eczematous dermatitis)
4) Acantholysis - Separation of epidermal cells (Pemphigus vulgaris)
5) Acanthosis - Epidermal hyperplasia - increased spinosum (Acanthosis nigricans)
Pigmented skin disorders
1) Albinism - normal melanocyte number with reduced melanin production due to low tyrosinase activity or defective tyrosine transport. Can also be caused by failure of neural crest cell migration during development. Increased risk of skin cancer
2) Melasma (cholasma) - hyperpigmentation associated with pregnancy (“mask of pregnancy”) or OCP use
3) Vitiligo - Irregular areas of complete depigmentation. Caused by autoimmune destruction of melanocytes
Acne
Obstructive and inflammatory disease of the pilosebaceous unit predominantly found on the face and trunk. Most common in adolescents but can occur at any age.
Atopic dermatitis (eczema)
Pruritic eruption, commonly on skin flexures. Often associated with other atopic diseases (asthma, allergic rhinitis)
usually starts on the face in infancy and often appears in antecubital fossae thereafter
Allergic contact dermatitis
Type 4 hypersensitivity reaction that follows exposure to allergen. Lesions occur at site of contact (nickel, poison ivy, neomycin)
Melanocytic nevus
Common mole. Benign, but melanoma can arise in congenital or atypical moles. Intradermal nevi are papular. Junctional nevi are flat macules.
Psoriasis
Papules and plaques with silvery scaling, especially on knees and elbows. Acanthosis with parakeratotic scaling (nuclei still in stratum corneum). Increased stratum spinosum, lower stratum granulosum.
Auspitz sign - pinpoint bleeding spots from exposure of dermal papillae when scales are ripped off. Can be associated with nail pitting and psoriatic arthritis
Rosacea
Inflammatory facial skin disorder characterized by erythematous papules and pustules, but no comedones. May be associated with facial flushing in response to external stimuli (alcohol, heat).
Chronic inflammatory changes may result in rhinophyma (bulbous deformation of nose)
Seborrheic keratosis
Flat, greasy, pigmented squamous epithelial proliferation with keratin-filled cysts (horn cysts).
Looks “stuck on.” Lesions occur on head, trunk, and extremities. Common benign neoplasm of older persons
Leser-Trelat sign - sudden appearance of multiple seborrheic keratoses, indicating an underlying malignancy (GI, lymphoid)
Verrucae
Warts; caused by HPV. Soft, tan-colored, cauliflower-like papules. Epidermal hyperplasia, hyperkeratosis, koilocytosis.
Condyloma acuminatum on genitals
Urticaria
Hives. Pruritic wheals that form after mast cell degranulation. Characterized by superficial dermal edema and lymphatic channel dilation
Impetigo
Very superficial skin infection. Usually from:
S. aureus
S. pyogenes
Highly contagious. Honey-colored crusting
Bullous impetigo has bullae caused by S. aureus
Cellulitis
Acute, painful, spreading infection of deeper dermis and subcutaneous tissues. Usually from:
S. pyogenes
S. aureus
Often starts with a break in skin from trauma or another infection
Erysipelas
Infection involving upper dermis and superficial lymphatics, usually from:
S. pyogenes
Presents with well-defined demarcation between infected and normal skin
Abscess
Collection of pus from a walled-off infection within deeper layers of skin. Offending organism is almost always:
S. aureus
Which is frequently methicillin resistant
Necrotizing fasciitis
Deeper tissue injury, usually from anaerobic bacteria or
S. pyogenes
results in crepitus from methane and CO2 production. “Flesh eating bacteria”
Causes bullae and a purple color to the skin
Staphylococcal Scaled Skin Syndrome
Exotoxin destroys keratinocyte attachments in stratum granulosum only (vs toxic epidermal necrolysis, which destroys epidermal-dermal junction)
Characterized by fever and generalized erythematous rash with sloughing of the upper layers of the epidermis that heals completely.
Seen in newborns and children, adults with renal insufficiency
herpes
Herpes virus infections (HSV1 and HSV2) of skin can occur anywhere from mucosal surfaces to normal skin. These include herpes labialis, herpes genitalis, herpetic whitlow (finger)
Molluscum contagiosum
Umbilicated papules caused by a poxvirus
While frequently seen in children, it may be sexually transmitted in adults
Varicella zoster virus
Causes varicella (chickenpox) and zoster (shingles). Varicella presents with multiple crops of lesions in various stages from vesicles to crusts.
Zoster is a reactivation of the virus in dermatomal distribution (unless it is disseminated)
Hairy leukoplakia
Irregular, white, painless plaques on tongue that cannot be scraped off. EBV mediated. Occurs in HIV+ patients, organ transplant recipients. Contrast with thrush (scrapable) and leukoplakia (precancerous)
Pemphigus vulgaris
Potentially fatal autoimmune skin disorder with IgG antibody against desmoglein (component of desmosomes)
Flaccid intraepidermal bullae caused by acantholysis (keratinocytes in stratum spinosum are connected by desmosomes); oral mucosa also involved
Bullous pemphigoid
less severe than PV.
Involved IgG antibodies against hemidesmosomes (epidermal basement membrane).
Tense blisters containing eosinophils affect skin but spare oral mucosa.
Immuno reveals linear pattern at epidermal-dermal junction.
Nikolsky sign (-)
Dermatitis herpetiformis
pruritic papules, vesicles, and bullae (often on elbows).
Deposits of IgA at tips of dermal papillae. Associated with celiac disease.
Erythema muliforme
Associated with infections (mycoplasma pneumoniae, HSV), drugs (sulfa drugs, B-lactams, phenytoin), cancers, autoimmune disorders.
Presents with multiple types of lesions – macules, papules, vesicles, target lesions (multiple rings with dusky center showing epithelial disruption).
SJS
Characterized by fever, bullae formation and necrosis, sloughing of skin. High mortality.
Typically 2 mucous membranes involved, and targetoid skin lesions may appear, as seen in EM.
Usually associated with adverse drug rxn.
More severe form with >30% body involvement is TEN (10-30% involvement is SJS-TEN).
Acanthosis nigricans
Epidermal hyperplasia causing symmetric, hyperpigmented thickening of skin, especially in axilla or on neck. Associated with hyperinsulinemia (diabetes, obesity, Cushing Syndrome), visceral malignancy (gastric adenocarcinoma)
Actinic keratosis
Premalignant lesions caused by sun exposure
Small, rough, erythematous or brownish papules or plaques
Risk of SCC is proportional to degree of epithelial dysplasia
Erythema nodosum
Painful inflammatory lesions of subcutaneous fat, usually on anterior shins. Often idiopathic, but can be associated with sarcoidosis, coccidioidomycosis, histoplasmosis, TB, strep infections, leprosy, Crohn disease)
Lichen Planus
Pruritic, Purple, Polygonal Planar Papules and Plaques are the 6 Ps of lichen Planus
Mucosal involvement manifests as Wickham striae (reticular white lines). Sawtooth infiltrate of lymphocytes at dermal-epidermal junction.
Associated with Hep C
Pityriasis rosea
“Herald patch” followed days later by other scaly erythematous plaques, often in a “Christmas tree” distribution. Multiple plaques with collarette scale. Self-resolving in 6-8 weeks
Sunburn
Acute cutaneous inflammatory reaction due to excessive UV irradiation. Causes DNA mutations, inducing apoptosis of keratinocytes
UVA is dominant in tanning and photoaging, UVB in sunburn
Can lead to impetigo, skin cancers (basal cell carcinoma, SCC, melanoma)
Basal cell carcinoma
Most common. Found in sun-exposed areas of body. Locally invasive, but rarely metastasizes.
Pink, pearly, nodules, commonly with telangiectasias, rolled borders, central crusting or ulceration.
BCCs also appear in nonhealing ulcers with infiltrating growth or as a scaling plaque (superficial BCC).
Basal cell tumors have palisading nuclei.
Squamous cell carcinoma
Second most common. Associated with excessive exposure to sunlight, immunosuppression, and sometimes arsenic exposure.
Commonly appears on face, lower lip, ears, hands. Locally invasive, may spread to lymph nodes, and will rarely metastasize.
Ulcerative red lesions with frequent scale. Associated with chronic draining sinuses. Histopath shows keratin pearls.
Actinic keratosis - A scaly plaque, is a precursor to SCC
Keratoacanthoma - A variant can go away quickly after growing quickly (4-6 weeks)
Melanoma
Common tumor with high risk of met.
S-100 tumor marker. Associated with sunlight exposure; fair-skinned peeps at higher risk. Depth of tumor correlates with metastatic risk.
Look for the ABCDEs Asymmetry Border irregularity Color variation Diameter > 6 mm Evolution over time
4 different types of melanoma
- Nodular
- Lentigo maligna
- Acral lentiginous
- Superficial spreading
Often driven by activating mutation in BRAF kinase.
Primary tx is excision with wide margins. Metastatic or unresectable melanoma in patients with BRAF V600E mutation may benefit from vemurafenib (BRAF kinase inhibitor)
