Derm/Musculoskeletal Flashcards
Epidermis Layers
Corneum Lucidum Granulosum Spinosum Basale "Californians Like Girls in String Bikinis"
Adherens junction
Below tight junction (between epithelial cells)
- Belt connecting actin cytoskeletons via Cadherins (Ca+2- dependent adhesion proteins
- Loss of E-cadherin= metastases
Desmosomes
Macula adherens providing structural support via keratin
- Autoantibodies–> pemphigus vulgaris*
Gap junction
Channel proteins= connexons
- Central channel= electrical, chemical communication
Integrins
Membrane proteins maintaining basement membrane
- Bind laminin in BM
Hemidesmosome
Connects Keratin in basal cell to underlying basement membrane
- Autoantibodies–> bullous pemphgoid*
Endochondrial ossification
Axial and appendicular skeleton
- Cartilaginous model laid down by chondrocytes
- Osteoblasts/clasts replace with woven bone
- Remodel to lamellar bone
**Woven bone in fractures, Paget’s disease
Membranous ossification
Calvarium, facial bones
- No cartilage model- woven bone directly formed
- Remodeled to woven bone
Cytokine stimulation of osteoblasts/clasts
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
Osteoblast activity
Alkaline Phosphatase levels (differentiate from liver Alk-Phos vis gel electrophoresis)
Osteoclast activity
Urinary deoxypyridinoline
Urinary hydroxyproline (also caused by meat consumption)
Tartrate-resistant acid phosphatase (breaks down bone)
Achondroplasia
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
Albright’s hereditary osteodystrophy
Pseudohypoparathyroidism 1A= end organ resistance to PTH (+ TSH, LH, FSH)
- Short stature
- short metatarsal, metacarpals
Osteopetrosis
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
Osteomalacia/rickets
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)
Paget’s disease
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)
McCune-Albright syndrome
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
Rheumatoid arthritis
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
Infectious arthritis
S. aureus, Streptococcus, Neisseria gonorrhoeae
- Synovitis
- Tenosynovitis
- Dermatitis (pustules)
Psoriatic arthritis
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
Ankylosing spondylitis
HLA-B27 association
Ankylosis (stiff spine d/t fusion of joints
Uveitis
Aortic regurgitation
Reactive arthritis= Reiter’s syndrome
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
Digital clubbing
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
Systemic Lupus erythematosus
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
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
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)
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
Polymyositis
- progressive symmetric proximal weakness in shoulders
- Endomysial inflammation
- CD8+ cells
Labs:
- Elevated CK, ANA+, Jo-1 antibodies
Treatment: steroids
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)
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
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
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
Parakeratosis
Hyperkeratosis with retention of nuclei in stratum corneum
- Seen in psoriasis, along with hyperkeratosis (thickness increased in corneum)
Acantholysis
Separation of epidermal cells
- Seen in pemphigus vulgaris= antibodies against desmoglein 3 (desmosomes between epidermal cells linking keratin skeletons))
Acanthosis
Epidermal hyperplasia (increase in spinosum) - Seen in acanthosis nigricans
Melasma (cholasma)
Hyperpigmentation associated with pregnancy (mask of pregnancy) and OCP use
Lentigo
Benign linear melanocyte hyperplasia (in epidermis, above basement membrane)
- vs Nevi= NESTS of melanocytes
Ephelis
Freckle
- Normal melanocyte number, increased melanin pigment production
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
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)
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)
Bullous pemphigoid
Autoimmune disorder
- IgG against hemidesmosomes (epidermal basement membrane binding)
- Linear immunofluorescence
- Eosinophils, tense blisters
- Spares mucosa
- Negative Nikolsky
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
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
Erythema nodosum
Inflammatory lesions of subcutaneous fat on anterior shins (painful)
Associated with:
- Sarcoidosis
- Coccidioidomycosis
- histoplasmosis
- TB
- Strep infections
- leprosy
- Corhn’s disease
- OCP
Lichen planus
Pruritic, Purple, Polygonal Planar papules
- Sawtooth infiltrate of lymphocytes at dermal-epidermal junction
Associated with hepatitis C
Pityriasis rosea
“Herald patch” with “Christmas tree” distribution
- Multiple plaques with collarette scale
Resolves in 6-8 weeks
Impetigo
Superifical skin infection
- S. aureus
- S. pyogenes
Honey colored crusting, contagious
- Also see these bacteria in cellulitis
Staph Scalded Skin Syndrome
Exotoxin from S. aureus–> destroys desmosomes (keratinocyte attachments in stratum granulosum ONLY)
Hair leukoplakia
White, painless plaques on tongue that CANNOT be scraped off (vs candida)
- EBV-mediated
- HIV+ patients
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)
Lipoxygenase
Membrane lipid–> Phospholipase A2 (blocked by corticosteroids)–> Arachidonic acid–> Lipooxygenase–> yields leukotrienes:
- LTB4= neutrophil chemotactic agent
- LTC4, D4, E4= constriction, increased vascular permeability
Cyclooxygenase
Membrane lipid–> phospholipase A2–> Arachidonic acid–> COX1/2–> Endoperoxides–>
- Prostacyclin (PGI2)
- Prostaglandins (PGE2, PGF2alpha)
- Thromboxane (TXA2)
NSAIDS
Reversible inhibit cyclooxygenase (1 + 2)
- Block prostaglandin synthesis
- *vs aspirin: blocks TXA2= good for anti-platelet aggregation, and prostaglandins
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
Acetaminophen
Reversible inhibition of COX in CNS (inactivated peripherally, therefore not Anti-inflammatory, only antipyretic and analgesic)
Bisphosponates
Pyrophosphate analogs
Bind hydroxyapatite in bone–> inhibit osteoclast activity
Tox: corrosive esophagitis, osteonecrosis of jaw
Allopurinol
Inhibits XO
- Increases concentrations of azathioprine, 6-MP
- Do NOT give salicylates (depress uric acid clearance)
Fuboxistat
Inhibits XO
Probenecid
Inhibits reabsorption of uric acid in PCT
- Avoid in patients with excess uric acid excretion
Colchicine
Binds, stabilizes tubulin–> inhibits polymerization–> impaired leukocyte chemotaxis, degranulation
- Do not give in elderly, renal dysfunction
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
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)
