Musculoskeletal - Skin - Connective Tissue_2 Flashcards
presentation of dermatomyositis?
similar to polymyositis, but also invovles malar rash, Gottron’s papules. heliotrope rash, shawl and face rash, mechanic’s hands
dermatomyositis carries ↑ risk of what?
occult malignancy
pathology in dermatomyositis?
perimysial inflammation and atrophy with CD4+ T cells
findings in polymyositis/dermatomyositis?
↑ CK • ANA (+) • anti-Jo-1 Ab (+)
treatment for polymyositis/dermatomyositis?
steroids
what is the frequency of myasthenia gravis?
most common NMJ disorder
frequency of lambert eaton myasthenic syndrome?
uncommon
pathophysiology of MG?
autoantibodies to postsynaptic AChR
pathophysiology of LEMS?
autoantibodies to presynaptic Ca++ channel →↓ ACh release
clinical presentation of MG?
ptosis • diplopia • weakness • worsens with muscle use
clinical presentation of LEMS?
proximal muscle weakness • improves with muscle use
MG associated with what?
thymoma • thymic hyperplasia
LEMS associated with what?
SCLC
what happens with AChE inhibitor administration in MG?
reversal of symptoms
what happens with AChE inhibitor administration in LEMS?
no effect
what is myositis ossificans?
metaplasia of skeletal muscle to bone following muscular trauma
myositis ossificans is most often seen where?
in upper or lower extremity
myositis ossificans may present how?
as suspicious mass at site of known trauma or as incidental finding on radiography
what happens in scleroderma (SS)?
excessive fibrosis and collagen deposition throughout the body
common manifestation of SS?
sclerosis of skin, manifesting as puffy and taut skin with absence of wrinkles • also sclerosis of renal, pulm, CV, GI systems
most likely cause of death in SS?
sclerosis of pulmonary system
epidemiology of SS?
75% female
2 major types of SS?
diffuse scleroderma • CREST syndrome
clinical features of diffuse scleroderma?
widespread skin involvement, rapid progression, early visceral involvement
marker for diffuse scleroderma?
anti-Scl-70 Ab (anti-DNA topoisomerase I Ab)
clinical features of CREST syndrome?
Calcinosis • Raynaud’s phenomenon • Esophageal dysmotility • Sclerodactyly • Telangiectasia
skin involvement in CREST syndrome?
limited skin involvement, often confined to fingers and face
clinical course of CREST syndrome relative do diffuse scleroderma?
more benign clinical course
marker for CREST syndrome?
anticentromere antibody
what is a macule?
flat lesion with well-circumscribed change in skin color <5mm
examples of macule?
freckle • labial macule
what is a patch?
macule >5mm
what is an example of a patch?
large birthmark (congenital nevus)
what is a papule?
elevated solid skin lesion <5mm
example of papule?
mole (nevus) • acne
what is a plaque?
papule >5mm
what is an example of derm plaque?
psoriasis
what is a derm vesicle?
small fluid containing blister <5mm
example of derm vesicle?
chickenpox (varicella) • shingles (zoster)
what is a bulla?
large fluid containing blister >5mm
example of bulla?
bullous pemphigoid
what is a pustule?
vesicle containing pus
example of pustule?
pustular psoriasis
what is wheal?
transient smooth papule or plaque
example of wheal?
hives (urticaria)
what is derm scale?
flaking off of stratum corneum
example of derm scale?
eczema • psoriasis • SCC
what is derm crust?
dry exudate
example of derm crust?
impetigo
what is hyperkeratosis?
↑ thickness of stratum corneum
example of hyperkeratosis?
psoriasis
what is parakeratosis?
hyperkeratosis with retention of nuclei in stratum corneum
example of parakeratosis?
psoriasis
what is acantholysis?
separation of epidermal cells
example of acantholysis?
pemphigus vulgaris
what is acanthosis?
epidermal hyperplasia [↑spinosum]
example of acanthosis?
acanthosis nigricans
what is dermatitis?
inflammation of the skin
example of dermatitis?
atopic dermatitis
pathogenesis of albinism?
normal number of melanocytes with ↓ melanin production due to ↓ tyrosinase activity • can also be caused by failure of neural crest cells to migrate during development
what is melasma (chloasma)?
hyperpigmentation associated with pregnancy (mask of pregnancy) or OCP use
what is vitiligo?
irregular areas of complete depigmentation
vitiligo is caused by what?
↓ in melanocytes
what are verrucae?
warts
verrucae are caused by what?
HPV
what do verrucae look like?
soft, tan colored, cauliflower like papules
microscopic features of verrucae?
epidermal hyperplasia • hyperkeratosis • koilocytosis
what are verrucae on genitals?
condyloma accuminatum
what is melanocytic nevus?
common mole
pathogenicity of melanocytic nevus?
benign, but melanoma can arise in congenital or atypical moles
intradermal nevi are what?
papular
junctional nevi are what?
flat macules
what is urticaria?
hives- pruritic wheals that form after mast cell degranulation
what is ephelis?
freckle
molecular features of ephelis?
normal number of melanocytes, ↑ melanin pigment
what is atopic dermatitis (eczema)?
pruritic eruption, commonly on skin flexures
atopic dermatitis is often associated with what?
other atopic diseases (asthma, allergic rhinitis)
course of atopic dermatitis?
usually starts on the face in infancy and often appears in the antecubital fossa thereafter
what is allergic contact dermatitis?
type IV HSR that follows exposure to allergen
where do lesions occur in allergic contact dermatitis?
at site of contact • (nickel, poison ivy, neomycin)
what is psoriasis?
papules and plaques with silvery scaling, especially on knees and elbows
microscopic features of psoriasis?
acanthosis with parakeratotic scaling (nuclei still in stratum corneum)
cellular features of psoriasis?
↑ stratum spinosum • ↓ stratum granulosum
what is Auspitz sign in psoriasis?
pinpoint bleeding spots from exposure of dermal papillae when scales are scraped off
psoriasis can be associated with what?
nail pitting and psoriatic arthritis
what is seborrheic keratosis?
flat, greasy, pigmented squamous epithelial proliferation with keratin filled cysts (horn cysts)
how does seborrheic keratosis look?
stuck on
lesions in seborrheic keratosis occur where?
on head, trunk, and extremities
incidence of seborrheic keratosis?
common benign neoplasm of older persons
what is the Leser-Trelat sign?
sudden appearance of multiple seborrheic keratoses, indicating an underlying malignancy (GI, lymphoid)
what is pemphigus vulgaris?
potentially fatal autoimmune skin disorder with IgG Ab against desmoglein 3 (1 and/or 3), a part of the desmosomes (needed for cell adhesion)
IF findings in pemphigus vulgaris?
Ab around epidermal cells in a reticular or net like pattern
dermatologic pathology findings in pemphigous vulgaris?
acantholysis- intraepidermal bullae causing flaccid blister involving the skin and oral mucosa
positive PE sign in pemphigus vulgaris?
Nikolsky’s sign (separation of the epidermis upon manual stroking of the skin)
what is bullous pemphigoid?
autoimmune disorder with IgG Ab against hemidesmosomes (epidermal basement membrane)
IF findings in bullous pemphigoid?
shows linear immunofluorescence
Bx findings in bullous pemphigoid?
eosinophils within tense blisters
how does bullous pemphigoid compare to pemphigus vulgaris?
similar to but less severe than PV • affects skin but spares oral mucosa • negative Nikolsky’s sign
presentation of dermatitis herpetiformis?
pruritic papules, vesicles, and bullae
cause of dermatitis herpetiformis?
deposits of IgA at the tips of dermal papillae
dermatitis herpetiformis is associated with what?
celiac disease
erythema multiforme is associated with what?
infections • drugs • cancers • autoimmune disease
infections associated with erythema multiforme?
Mycoplasma pneumoniae • HSV
drugs associated with erythema multiforme?
sulfa drugs • β lactams • phenytoin
erythema multiforme presents with what?
multiple types of lesions- macules, papules, vesicles, and target lesions
Stevens-Johnson syndrome is characterized by what?
fever • bulla formation and necrosis • sloughing of skin • high mortality rate
skin lesions involved in Stevens-Johnson syndrome?
typically 2 mucus membranes are involved and skin lesions may appear like targets as seen in erythema multiforme
stevens johnson syndrome usually associated with what?
adverse drug reaction
what is the more severe form of stevens johnson syndrome?
> 30% of body surface area involved→toxic epidermal necrolysis
what is acanthosis nigricans?
epidermal hyperplasia causing symmetrical, hyperpigmented, velvety thickening of skin, especially on neck or in axilla
acanthosis nigricans is associated with what?
hyperinsulinemia (diabetes, obesity, Cushings) • visceral malignancy
what is actinic keratosis?
premalignant lesions caused by sun exposure
how does actinic keratosis look?
small, rough, erythematous or brownish papules or plaques
how is risk of cancer in actinic keratosis assessed?
risk of SCC is proportional to degree of epithelial dysplasia
what is erythema nodosum?
inflammatory lesions of subcutaenous fat, usually on the anterior shins
erythema nodosum is associated with what?
sarcoidosis • coccidioidomycosis • histoplasmosis • TB • streptococcal infections • leprosy • crohn’s disease
what are the 6 P’s of lichen planus?
pruritic • purple • polygonal • planar • papules
histopathology of lichen planus?
sawtooth infiltrate of lymphocytes at dermal-epidermal junction
lichen planus is associated with what?
hepatitis C
what is the presentation of pityriasis rosea?
herald patch followed days later by christmas tree distribution
what does pityriasis rosea look like?
multiple plaques with collarette scale
course of pityriasis rosea?
self resolving in 6-8 weeks
what happens in sunburn?
UV radiation causes DNA mutations, inducing apoptosis of keratinocytes
which type of light is dominant in tanning and photoaging?
UVA
which type of light is dominant in sunburn?
UVB
sunburn can lead to what?
impetigo and skin cancers
which skin cancers can be caused by sunburn?
basal cell carcinoma • SCC • melanoma
what is impetigo?
very superficial skin infection
organisms that cause impetigo?
usually S aureus or S pyogenes
transmissibility of impetigo?
highly contagious
appearance of impetigo?
honey colored crusting
features of bullous impetigo?
has bullae and is usually caused by S aureus
what is cellulitis?
acute, painful, spreading infection of dermis and subcutaneous tissues
organisms that cause cellulitis?
S pyogenes or S aureus
cellulitis often starts with what?
a break in skin from trauma or another infection
what is necrotizing fasciitis?
deeper tissue injury usually from anaerobic bacteria or S pyogenes
necrotizing fasciitis results in what?
crepitus from methane and CO2 production
necrotizing fasciitis AKA?
flesh eating bacteria
skin appearance in necrotizing fasciitis?
bullae and purple color
what happens in staphylococcal scalded skin syndrome (SSSS)?
exotoxin destroys keratinocyte attachments in the stratum granulosum only
difference between SSSS and TEN?
SSSS destroys stratum granulosum only, • TEN destroys dermal-epidermal junction
SSSS characterized by what?
fever • generalized erythematous rash with sloughing of the upper layers of the epidermis that heals completely
SSSS seen in who?
infants and children
what is hairy leukoplakia?
white, painless plaques on the tongue that cannot be scraped off
virus that mediates hairy leukoplakia?
EBV
hairy leukoplakia occurs in who?
HIV patients
what is the most common skin cancer?
basal cell carcinoma
basal cell carcinoma found where?
sun exposed areas of body
severity of basal cell carcinoma?
locally invasive, but almost never metastasizes
appearance of basal cell carcinoma?
pink, pearly nodules, commonly with telangiectasias, rolled borders, and central crusting or ulceration • or • nonhealing ulcers with infiltrating growth • or • scaling plaque
histological features of BCCs?
palisading nuclei
what is the second most common skin cancer?
SCC
SCC of skin is associated with what?
excessive exposure to sunlight, immunosuppression, arsenic exposure
SCC of skin commonly appears where?
face, lower lip, ears, hands
severity of SCC of skin?
locally invasive, but may spread to lymph nodes • rarely metastasizes
appearance of SCC of skin?
ulcerative red lesions with frequent scale • chronic draining sinuses
histopathology of SCC of skin?
keratin pearls
which scaly plaque is a precursor to SCC of skin?
actinic keratosis
which variant of skin SCC grows rapidly for 4-6 weeks and may regress spontaneously over months?
keratoacanthoma
which skin cancer is a common tumor with significant risk of metastasis?
melanoma
tumor marker associated with melanoma?
S-100
predisposing factors for melanoma?
sunlight exposure • fair-skinned persons at ↑ risk
risk of mets in melanoma is proportional to what?
depth of tumor
what should you look for in melanoma?
ABCDEs: • Asymmetry • Border irregularity • Color variation • Diameter>6mm • Evolution over time
4 types of melanoma?
superficial spreading melanoma • nodular melanoma • lentigo maligna melanoma • acrolentiginous melanoma
genetics of melanoma?
often driven by activating mutation in BRAF kinase
primary treatment for melanoma?
excision with appropriately wide margins
metastatic or unresectable melanoma in patients with BRAF V600E mutation may benefit from what?
vemurafenib, a BRAF kinase inhibitor
lipoxygenase pathway yields what?
leukotrienes
function of LTB4?
neutrophil chemotactic agent
LTC4, LTD4, LTE4 function in what?
bronchoconstriction • vasoconstriction • contraction of smooth muscle • ↑ vascular permeability
action of PGI2?
inhibits platelet aggregation and promotes vasodilation
effect of corticosteroids on arachidonic acid products?
inhibits PLA2 • inhibits protein synthesis →↓ COX
effect of NSAIDs, aspirin, acetaminophen, COX-2 inhibitors on arachidonic acid products?
inhibit COX enzymes to ↓ formation of endoperoxides PGG2 and PGH2
effect of zileuton on arachidonic acid products?
inhibits lipoxygenase to ↓ formation of hydroperoxides (HPETEs)
action of TXA2?
↑platelet aggregation • ↑ vascular tone • ↑ bronchial tone
action of PGE2 and PGF2?
↑ uterine tone • ↓ vascular tone • ↓ bronchial tone
action of prostacyclin (PGI2)?
↓ platelet aggregation • ↓ vascular tone • ↓ bronchial tone • ↓ uterine tone
effect of zafirleukast and monteleukast on arachidonic acid products?
block actions of LTC4 and LTD4 at receptors
MOA of aspirin?
irreversibly inhibits COX1 and COX2 by acetylation→↓ synthesis of TXA2 and PGs • NSAID
effect of aspirin on blood labs?
↑ bleeding time • no Δ in PT, PTT
clinical use of low dose aspirin?
<300mg/d ↓ platelet aggregation
clinical use of intermediate dose aspirin?
300-2400mg/d→ antipyretic and analgesic
clinical use of high dose aspirin?
2400-4000mg/d→anti-inflammatory
toxicity of aspirin?
gastric ulceration • tinnitus • stimulates respiratory centers causing hyperventilation and respiratory alkalosis
chronic use of aspirin can lead to what?
acute renal failure • interstitial nephritis • upper GI bleeding
risk of what in children with aspirin use?
Reyes syndrome when used to treat viral infection
which drugs are NSAIDs?
ibuprofen • naproxen • indomethacin • ketorolac • diclofenac
MOA of NSAIDs?
reversibly inhibit COX1 and COX2→ block PG synthesis
clinical use of NSAIDs?
antipyretic • analgesic • anti-inflammatory
special use of indomethacin?
close a PDA
toxicity of NSAIDs?
interstitial nephritis • gastric ulcer • renal ischemia
MOA of COX2 inhibitors (celecoxib)?
reversibly inhibit COX2 found in inflammatory cells and vascular endothelium • spares COX1 to protect gastric mucosa and platelet function
clinical use of celecoxib?
RA and OA, patients with gastritis or ulcers
toxicity of celecoxib?
↑risk of thrombosis • sulfa allergy
MOA of acetaminophen?
reversibly inhibits COX mostly in CNS, is inactivated peripherally
clinical use of acetaminophen?
antipyretic • analgesic • not anti-inflammatory • used instead of aspirin in children with viral infection to avoid reyes syndrome
toxicity of acetaminophen?
OD→hepatic necrosis; acetaminophen metabolite depletes glutathione and forms toxic tissue adducrs in liver
antidote for acetaminophen overdose?
N-acetylcysteine- regenerates glutathione
which drugs are bisphosphonates?
alendronate, other -dronates
MOA of bisphosphonates?
pyrophosphate analogs; bind hydroxyapatite in bone, inhibiting osteoclast activity
clinical use of bisphosphonates?
osteoporosis • hypercalcemia • pagets disease of bone
toxicity of bisphosphonates?
corrosive esophagitis • osteonecrosis of the jaw
MOA of allopurinol?
inhibits xanthine oxidase, ↓ conversion of xanthine to uric acid • used in lymphoma and leukemia to prevent tumor lysis associated urate nephropathy
PK considerations for allopurinol?
↑ concentrations of azathiprine and 6-MP
CI with allopurinol?
do not give salicylates (↓ urate clearance)
MOA of febuxostat?
inhibits xanthine oxidase
MOA of probenecid?
inhibits reabsorption of urate in PCT (also inhibits secretion of penicillin)
MOA of colchicine?
binds and stabilizes tubulin to inhibit polymerization, impairing leukocyte chemotaxis and degranulation
AE of colchicine?
GI side effects, especially is given PO
which are the NSAIDs for acute gout?
naproxen, indomethacin
ROA for glucocorticoids for acute gout?
oral or intraarticular
immune precaution for all TNF-α inhibitors?
all predispose to infection including reactivation of latent TB since TNF blockade prevents activation of macrophages and destruction of phagocytosed microbes
which drugs are the TNFα inhibitors?
etanercept • infliximab, adalimumab
MOA of etanercept?
fusion protein (receptor for TNF-α + IgG1 Fc), produced by recombinant DNA • decoy receptor
clinical use of etanercept?
RA • psoriasis • ankylosing spondylitis
MOA of infliximab, adalimumab?
anti TNFα monoclonal Ab
clinical use of infliximab and adalimumab?
crohns • RA • ankylosing spondylitis • psoriasis
