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Flashcards in Derm/Musculoskeletal Deck (63)
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1
Q

Epidermis Layers

A
Corneum
Lucidum
Granulosum
Spinosum
Basale
"Californians Like Girls in String Bikinis"
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
3
Q

Desmosomes

A

Macula adherens providing structural support via keratin

- Autoantibodies–> pemphigus vulgaris*

4
Q

Gap junction

A

Channel proteins= connexons

- Central channel= electrical, chemical communication

5
Q

Integrins

A

Membrane proteins maintaining basement membrane

- Bind laminin in BM

6
Q

Hemidesmosome

A

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

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

8
Q

Membranous ossification

A

Calvarium, facial bones

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

10
Q

Osteoblast activity

A

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

11
Q

Osteoclast activity

A

Urinary deoxypyridinoline

Urinary hydroxyproline (also caused by meat consumption)

Tartrate-resistant acid phosphatase (breaks down bone)

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

13
Q

Albright’s hereditary osteodystrophy

A

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

  • Short stature
  • short metatarsal, metacarpals
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

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)

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)
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
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
19
Q

Infectious arthritis

A

S. aureus, Streptococcus, Neisseria gonorrhoeae

  • Synovitis
  • Tenosynovitis
  • Dermatitis (pustules)
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

21
Q

Ankylosing spondylitis

A

HLA-B27 association

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

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
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
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
25
Q

Sarcoidosis

A

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
Q

Polymyalgia rheumatica

A

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
Q

Dermatomyositis

A
  • 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
Q

Polymyositis

A
  • progressive symmetric proximal weakness in shoulders
  • Endomysial inflammation
  • CD8+ cells

Labs:
- Elevated CK, ANA+, Jo-1 antibodies

Treatment: steroids

29
Q

Lambert-Eaton Myasthenic syndrome

A

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
Q

Crises in Myasthenia Gravis

A

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
Q

Scleroderma

A

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
Q

Juvenile hemangioma

A

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
Q

Parakeratosis

A

Hyperkeratosis with retention of nuclei in stratum corneum

- Seen in psoriasis, along with hyperkeratosis (thickness increased in corneum)

34
Q

Acantholysis

A

Separation of epidermal cells
- Seen in pemphigus vulgaris= antibodies against desmoglein 3 (desmosomes between epidermal cells linking keratin skeletons))

35
Q

Acanthosis

A
Epidermal hyperplasia (increase in spinosum)
- Seen in acanthosis nigricans
36
Q

Melasma (cholasma)

A

Hyperpigmentation associated with pregnancy (mask of pregnancy) and OCP use

37
Q

Lentigo

A

Benign linear melanocyte hyperplasia (in epidermis, above basement membrane)
- vs Nevi= NESTS of melanocytes

38
Q

Ephelis

A

Freckle

- Normal melanocyte number, increased melanin pigment production

39
Q

Psoriasis

A

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
Q

Seborrhaic keratosis

A

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
Q

Pemphigus vulgaris

A

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
Q

Bullous pemphigoid

A

Autoimmune disorder

  • IgG against hemidesmosomes (epidermal basement membrane binding)
  • Linear immunofluorescence
  • Eosinophils, tense blisters
  • Spares mucosa
  • Negative Nikolsky
43
Q

Dermatitis herpetiformis

A

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
Q

Erythema multiforme

A

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
Q

Erythema nodosum

A

Inflammatory lesions of subcutaneous fat on anterior shins (painful)

Associated with:

  • Sarcoidosis
  • Coccidioidomycosis
  • histoplasmosis
  • TB
  • Strep infections
  • leprosy
  • Corhn’s disease
  • OCP
46
Q

Lichen planus

A

Pruritic, Purple, Polygonal Planar papules
- Sawtooth infiltrate of lymphocytes at dermal-epidermal junction

Associated with hepatitis C

47
Q

Pityriasis rosea

A

“Herald patch” with “Christmas tree” distribution
- Multiple plaques with collarette scale

Resolves in 6-8 weeks

48
Q

Impetigo

A

Superifical skin infection

  • S. aureus
  • S. pyogenes

Honey colored crusting, contagious
- Also see these bacteria in cellulitis

49
Q

Staph Scalded Skin Syndrome

A

Exotoxin from S. aureus–> destroys desmosomes (keratinocyte attachments in stratum granulosum ONLY)

50
Q

Hair leukoplakia

A

White, painless plaques on tongue that CANNOT be scraped off (vs candida)

  • EBV-mediated
  • HIV+ patients
51
Q

Melanoma

A

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
Q

Lipoxygenase

A

Membrane lipid–> Phospholipase A2 (blocked by corticosteroids)–> Arachidonic acid–> Lipooxygenase–> yields leukotrienes:

  • LTB4= neutrophil chemotactic agent
  • LTC4, D4, E4= constriction, increased vascular permeability
53
Q

Cyclooxygenase

A

Membrane lipid–> phospholipase A2–> Arachidonic acid–> COX1/2–> Endoperoxides–>

  • Prostacyclin (PGI2)
  • Prostaglandins (PGE2, PGF2alpha)
  • Thromboxane (TXA2)
54
Q

NSAIDS

A

Reversible inhibit cyclooxygenase (1 + 2)

  • Block prostaglandin synthesis
  • *vs aspirin: blocks TXA2= good for anti-platelet aggregation, and prostaglandins
55
Q

Celecoxib

A

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
Q

Acetaminophen

A

Reversible inhibition of COX in CNS (inactivated peripherally, therefore not Anti-inflammatory, only antipyretic and analgesic)

57
Q

Bisphosponates

A

Pyrophosphate analogs
Bind hydroxyapatite in bone–> inhibit osteoclast activity

Tox: corrosive esophagitis, osteonecrosis of jaw

58
Q

Allopurinol

A

Inhibits XO

  • Increases concentrations of azathioprine, 6-MP
  • Do NOT give salicylates (depress uric acid clearance)
59
Q

Fuboxistat

A

Inhibits XO

60
Q

Probenecid

A

Inhibits reabsorption of uric acid in PCT

- Avoid in patients with excess uric acid excretion

61
Q

Colchicine

A

Binds, stabilizes tubulin–> inhibits polymerization–> impaired leukocyte chemotaxis, degranulation
- Do not give in elderly, renal dysfunction

62
Q

TNF-alpha inhibitors

A

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
Q

Drug-induced lupus

A

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)