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Derm/Musculoskeletal Flashcards

1
Q

Epidermis Layers

A 
Corneum
Lucidum
Granulosum
Spinosum
Basale
"Californians Like Girls in String Bikinis"
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2
Q

Adherens junction

A

Below tight junction (between epithelial cells)

  • Belt connecting actin cytoskeletons via Cadherins (Ca+2- dependent adhesion proteins
  • Loss of E-cadherin= metastases
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3
Q

Desmosomes

A

Macula adherens providing structural support via keratin

- Autoantibodies–> pemphigus vulgaris*

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4
Q

Gap junction

A

Channel proteins= connexons

- Central channel= electrical, chemical communication

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5
Q

Integrins

A

Membrane proteins maintaining basement membrane

- Bind laminin in BM

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6
Q

Hemidesmosome

A

Connects Keratin in basal cell to underlying basement membrane
- Autoantibodies–> bullous pemphgoid*

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7
Q

Endochondrial ossification

A

Axial and appendicular skeleton

  1. Cartilaginous model laid down by chondrocytes
  2. Osteoblasts/clasts replace with woven bone
  3. Remodel to lamellar bone

**Woven bone in fractures, Paget’s disease

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8
Q

Membranous ossification

A

Calvarium, facial bones

  1. No cartilage model- woven bone directly formed
  2. Remodeled to woven bone
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9
Q

Cytokine stimulation of osteoblasts/clasts

A

TGF= increase osteoblasts, collagen synthesis
- Induce osteoclast apoptosis

IGF-1= osteoblast replication, collagen synthesis
- Inhibits MMP-13 (metalloprotease)–> decreased collagen breakdown

IL-1= stimulates osteoclast activity

RANK-L= receptor for activated nuclear factor Kappa-beta Ligand
- PTH–> Osteoblasts produce RANK-L–> stimulate osteoclast activity

M-CSF= macrophage colony stimulating factor
- Secreted by osteoblasts to activate osteoclast formation/differentiation

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10
Q

Osteoblast activity

A

Alkaline Phosphatase levels (differentiate from liver Alk-Phos vis gel electrophoresis)

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11
Q

Osteoclast activity

A

Urinary deoxypyridinoline

Urinary hydroxyproline (also caused by meat consumption)

Tartrate-resistant acid phosphatase (breaks down bone)

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12
Q

Achondroplasia

A

Failure of longitudinal bone growth (endochondrial ossification)

  • -> short limbs
  • Membranous ossification NOT affected (Head disproportionately large)

Constitutive activation of FGFR3–> inhibit chondrocyte proliferation

85% sporadic, advanced paternal age
15% autosomal dominant inheritance

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13
Q

Albright’s hereditary osteodystrophy

A

Pseudohypoparathyroidism 1A= end organ resistance to PTH (+ TSH, LH, FSH)

  • Short stature
  • short metatarsal, metacarpals
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14
Q

Osteopetrosis

A

Failure of normal bone resorption d/t defective osteoclasts

  • Thickened, dense bone
  • Bone fills marrow–> pancytopenia, extramedullary hematopoiesis

Mutation in osteoclasts- can’t generate acidic environment (ex: carbonic anhydrase II)

Symptoms:

  • Cranial nerve impingement, palsies d/t narrow foramina
  • Bone fractures

Bone marrow transplant= curative

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15
Q

Osteomalacia/rickets

A

Vitamin D deficiency (poor diet, low sun, GI malabsorption)

  • Defective mineralization (calcification) of osteoid (osteoid matrix accumulation around trabeculae)
  • Soft bones–> bow out

Hyperactivity of osteoblasts–> see elevated Alk phos
- Secondary hyperparathyroidism (low Ca+2, phosphate)

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16
Q

Paget’s disease

A

Disordered bone remodeling:

1) Osteoclast activity increased (RANK-L, M-CSF increased)
2) Osteoblast activity increases
3) Fibroblasts, endothelial cells activated-> vascularization

Labs:
- Elevated alk-phos

Symptoms:

  • Mosaic “woven” bone
  • Increased blood flow d/t AV shunting (increased blood demand from bones–> high output heart failure
  • Increased hat size
  • Hearing loss (auditory foramina narrowing)
    • Increased risk of osteogenic sarcoma (persistant bone pain unresponsive to OTC analgesics)
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17
Q

McCune-Albright syndrome

A

Form of polyostic fibrous dysplasia:
- Bone replaced by fibroblasts, collagen, irregular bony trabeculae

PLUS:

  • Multiple bone lesions
  • Endocrine abnormalities (precocious puberty)
  • Cafe-au-lait spots
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18
Q

Rheumatoid arthritis

A

Type III hypersensitivity reaction: inflammatory destruction of synovial joints (pannus formation):

  • MCP, PIP–> ulnar deviation (no DIP involvement)
  • Baker’s cyst

80% positive Rheumatoid Factor (anti-IgG antibody, Fc portion)
** Anti-cyclic citrullinated peptide antibody most specific

Associated with HLA-DR4

Systemic involvement:

  • Fever
  • Fatigue
  • Pleuritis
  • Pericarditis
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19
Q

Infectious arthritis

A

S. aureus, Streptococcus, Neisseria gonorrhoeae

  • Synovitis
  • Tenosynovitis
  • Dermatitis (pustules)
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20
Q

Psoriatic arthritis

A 
Seronegative spondylarthropathy (no RF)
- HLA-B27 (HLA MHC class I)

Joint pain, stiffness associated with psoriasis

  • Asymmetric, patchy
  • Dactylitis (sausage fingers)
  • Pencil in cup deformity

Seen in < 1/3 patients with psoriasis

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21
Q

Ankylosing spondylitis

A

HLA-B27 association

Ankylosis (stiff spine d/t fusion of joints
Uveitis
Aortic regurgitation

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22
Q

Reactive arthritis= Reiter’s syndrome

A

HLA-B27 association

Conjunctivitis, anterior uveitis
Urethritis
Arthritis

May also see:

  • Mouth ulcerations, circinate balanitis, keratoderma blennorrhagicum (vesicles and scale)
  • axial involvement in ~20%= sacroilitis
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23
Q

Digital clubbing

A

Drumstick fingers with flattened nail folds, shininess of nail distal end
- Spongy, flutuant nail beds

Due to:

  • Lung disease (hypoxia): lung cancer, TB, CF, bronchiectasis, pulm HTN, empyema, chornic lung disease
  • Heart disease: congenital cyanotic disease, bacterial endocaditis
  • Other: IBD, Crohn/UC, hyperthyroidism, malabsorption

Pathophys:

  • Increased peripheral megakaryocytes, platelet clumps–> PDGF–> vascularization
  • Prostaglandin E2–> platelet EP3 receptor
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24
Q

Systemic Lupus erythematosus

A

90% female, 14-45
Most severe in black women
C1-complement component deficiency

Presentation:

  • Fever, fatigue, weight loss
  • Libman-Sacks endocarditis
  • Hilar adenopathy
  • Raynaud’s phenomenon
  • Nephritis (diffuse proliferative= nephritic or membranous= nephrotic)

Screen:

  • False postivie RPR/VDRL d/t APL (antiphospholipid antibodies)
  • ANA (antinucelar antibodies): sensitive
  • Anti-dsDNA: specific, poor prognosis
  • Anti-Smith (anti-SM): specific, not prognostic
  • Antibodies against RBCs (Type II hypersensitvity)–> autoimmune hemolysis (warm IgG, direct Coomb’s, spherocytosis)
  • Anti-histone antibodies: seen in drug-induced lupus (slow acetylators: phase II in liver; seen with hydralazine, procainamide, INH)
  • Anti snRNPs (spliceosome): seen in multiple connective tissue diseases
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25
Sarcoidosis
Mostly black females Immune-mediated widespread noncaseating granulomas - Elevated serum ACE Symptoms: - Enlarged lymph node - CXR: bilateral hilar lymphadenopathy, reticular opacities Associated with: - Restrictive lung disease (interstitial fibrosis) - Erythema nodosum - Bell's palsy - Epithelial granulomas (microscopic Schaumann and asteroid bodies) - Uveitis - Hypercalcemia ** due to epithelioid macrophages--> 1-alpha-hydroylase mediated vitamin D activation Treatment: Steroids
26
Polymyalgia rheumatica
Women > 50 years: - Pain, stiffness in shoulders and hips - fever, malaise, weight loss - No muscle weakness associated with temporal (giant cell) arteritis Elevated ESR, normal CK Treatment: rapid response to low-dose corticosteroids (vs GCA that requires high dose steroids)
27
Dermatomyositis
- Symmetric proximal weakness (shoulders) - Malar rash - Grotton's papules - Heliotrope rash Histo: - Perimysial inflammation - Atrophy - CD4+ infiltration Labs: - Elevated CK, ANA+, Jo-1 antibodies ** associated with malignancy Tx: steroids
28
Polymyositis
- progressive symmetric proximal weakness in shoulders - Endomysial inflammation - CD8+ cells Labs: - Elevated CK, ANA+, Jo-1 antibodies Treatment: steroids
29
Lambert-Eaton Myasthenic syndrome
Autoantibodies to presynaptic Ca+2 channels--> decreased Ach release Clinical: proximal muscle weakness IMPROVING with use (vs MG) Associated with SCLC No effect on course with AchE-I (vs MG)
30
Crises in Myasthenia Gravis
MG= autoantibodies to postsynaptic Ach receptor - decreased EPP (end-plate potential) Myasthenic crisis= not enough AChE-I administered (edrophonium tx will reverse symptoms) Cholinergic crisis= excess AChE-I administered - -> refractory depolarization--> weakness NOT responsive to edrophonium - Treatment: Pralidoxime= reactivates AchE (diazempam, atropine) Side-effects of MG treatment= cholinergic overdose (GI symptoms, excess lacrimation) - Treat with Scopalamine
31
Scleroderma
Fibrosis, collagen deposition disease - 75% female Skin: puffy, taut (beaked nose, pressure atrophy) Renal: flea-bitten; glomerular hemorrhage, necrosis Pulmonary: pulmonary fibrosis, HTN - Fine inspiratory crackles at bases GI: esophageal dilation, gastric dilation or Watermelon stomach, pseduodiverticula Diffuse scleroderma: Scl-70 antibodies (anti-DNA topoisomerase I): BAD CREST syndrome: anti-centromere antibdy) - Calcinosis - Raynaud's - Esophageal dysmotility - Sclerodactyly - Telangiectasias
32
Juvenile hemangioma
Benign cutaneous strawberry-like tumor at birth - Unencapsulated thin-walled capillaries - Multiple possible. found in: skin, subcutaneous tissue, oral mucosa, lips (liver, spleen, kidneys) - Fade by 1-3 years
33
Parakeratosis
Hyperkeratosis with retention of nuclei in stratum corneum | - Seen in psoriasis, along with hyperkeratosis (thickness increased in corneum)
34
Acantholysis
Separation of epidermal cells - Seen in pemphigus vulgaris= antibodies against desmoglein 3 (desmosomes between epidermal cells linking keratin skeletons))
35
Acanthosis
``` Epidermal hyperplasia (increase in spinosum) - Seen in acanthosis nigricans ```
36
Melasma (cholasma)
Hyperpigmentation associated with pregnancy (mask of pregnancy) and OCP use
37
Lentigo
Benign linear melanocyte hyperplasia (in epidermis, above basement membrane) - vs Nevi= NESTS of melanocytes
38
Ephelis
Freckle | - Normal melanocyte number, increased melanin pigment production
39
Psoriasis
CD4+ activated by APC cells in skin--> CD8+ cell activation - CD4+, CD8+, dendritic cells, keratinocytes interact--> TNF, IL-12, IFN-gamma, keratinocyte growth factors - -> keratinocyte proliferation, inflammation, angiogenesis Histo: - Increased stratum spinosum with Rete ridge elongation - Decreased stratum granulosum - Neutrophils--> spongiotic clusters in superficial parakeratotic stratum corneum Symptoms: - salmon-colored Papules, plaques on elbows, knees, gluteal cleft, lumbosacral area, glans penis, scalp - Silvery scale - Nail pitting - Auspitz sign= pinpoint bleeds when scales scraped off
40
Seborrhaic keratosis
Epithelial proliferation with keratin-filled cysts - Look "stuck on" - Head, neck, extremities Leser-Trelat sign= sudden appearance of multiple seborrheic keratoses - Underlying malignancy (GI, lymphoid)
41
Pemphigus vulgaris
Autoimmune disorder - IgG against desmoglein 3 (desmosomes) - Immunofluorescent netlike pattern - Skin and oral mucosa - Positive Nikolsky sign (separation of epidermis on manual stroking of skin)
42
Bullous pemphigoid
Autoimmune disorder - IgG against hemidesmosomes (epidermal basement membrane binding) - Linear immunofluorescence - Eosinophils, tense blisters - Spares mucosa - Negative Nikolsky
43
Dermatitis herpetiformis
Associated with Celiac disease IgA deposits at tips of dermal papillae--> pruritic papules, vesicles, bullae Bilateral, symmetric presentation on extensor surfaces, elbows, knees, upper back, buttocks
44
Erythema multiforme
Multiple lesions: macules, papules, vesicles, target lesions (rings, dusky center with epithelial disruption Associated with: - Infections: mycoplasma, HSV - Sulfa drugs, beta-lactams, phenytoin - cancer - autoimmune disease
45
Erythema nodosum
Inflammatory lesions of subcutaneous fat on anterior shins (painful) Associated with: - Sarcoidosis - Coccidioidomycosis - histoplasmosis - TB - Strep infections - leprosy - Corhn's disease - OCP
46
Lichen planus
Pruritic, Purple, Polygonal Planar papules - Sawtooth infiltrate of lymphocytes at dermal-epidermal junction Associated with hepatitis C
47
Pityriasis rosea
"Herald patch" with "Christmas tree" distribution - Multiple plaques with collarette scale Resolves in 6-8 weeks
48
Impetigo
Superifical skin infection - S. aureus - S. pyogenes Honey colored crusting, contagious - Also see these bacteria in cellulitis
49
Staph Scalded Skin Syndrome
Exotoxin from S. aureus--> destroys desmosomes (keratinocyte attachments in stratum granulosum ONLY)
50
Hair leukoplakia
White, painless plaques on tongue that CANNOT be scraped off (vs candida) - EBV-mediated - HIV+ patients
51
Melanoma
S-100 tumor marker (neural crest cell origin) p16 loss of function Activation of BRAF kinase (V600E) Tx: excision with wide margins (Mos Micrographic surgery)
52
Lipoxygenase
Membrane lipid--> Phospholipase A2 (blocked by corticosteroids)--> Arachidonic acid--> Lipooxygenase--> yields leukotrienes: - LTB4= neutrophil chemotactic agent - LTC4, D4, E4= constriction, increased vascular permeability
53
Cyclooxygenase
Membrane lipid--> phospholipase A2--> Arachidonic acid--> COX1/2--> Endoperoxides--> - Prostacyclin (PGI2) - Prostaglandins (PGE2, PGF2alpha) - Thromboxane (TXA2)
54
NSAIDS
Reversible inhibit cyclooxygenase (1 + 2) - Block prostaglandin synthesis * *vs aspirin: blocks TXA2= good for anti-platelet aggregation, and prostaglandins
55
Celecoxib
COX-2 inhibtor - Reversible - Found in inflammatory cells, vascular endothelium - Spares COX-1 (maintain GI mucosa) - Spares platelet function as TXA2 depends on COX-1--> increased risk of thrmobosis
56
Acetaminophen
Reversible inhibition of COX in CNS (inactivated peripherally, therefore not Anti-inflammatory, only antipyretic and analgesic)
57
Bisphosponates
Pyrophosphate analogs Bind hydroxyapatite in bone--> inhibit osteoclast activity Tox: corrosive esophagitis, osteonecrosis of jaw
58
Allopurinol
Inhibits XO - Increases concentrations of azathioprine, 6-MP - Do NOT give salicylates (depress uric acid clearance)
59
Fuboxistat
Inhibits XO
60
Probenecid
Inhibits reabsorption of uric acid in PCT | - Avoid in patients with excess uric acid excretion
61
Colchicine
Binds, stabilizes tubulin--> inhibits polymerization--> impaired leukocyte chemotaxis, degranulation - Do not give in elderly, renal dysfunction
62
TNF-alpha inhibitors
Etanercept= fusion protein (TNF-alpha receptor and IgG1Fc) - RA, psoriasis, ankylosing spondylitis Infliximab, adalimumab= anti-TNF-alpha monoclonal antibody - Crohn's disease, RA, ankylosing spondylitis, psoriasis ** Can reactivate latent TB
63
Drug-induced lupus
Seen with slow acetylators (phase II N-acetylation) - Hydralazine - Procainamide - INH Form ANA (anti-histone antibodies) without having previous history of SLE (just develop low-grade fever, joint pain, erythematous rash)

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