Exam 2 Flashcards
Treatment for Furuncle/Carbuncle
– almost always caused by Staphylococcus aureus
– symptoms: systemic. impaired defense, cellulitits
– Empiric treatment should cover MRSA
– CA-MRSA sensitive to TMP-SMX
– CA-MSSA and streptococcus sensitive to cephalexin
SIRS criteria
Two of the following conditions:
1.) Temp above 38 or below 36
2.) HR above 90bpm
3.) RR above 20
4.) WBC above 12,000 or below 4,000 or >10% banded neutrophils
Sepsis criteria
SIRS criteria plus present source of infection
1.) CT scan of brain multiple diffuse hyperdense foci
2.) CT Scan of chest– bilateral patchy areas of consolidation and ground-glass opacities in lungs, small focal effusions, pleural effusions
Staphylococcus aureus sepsis
– infects all tissue of the body
– Toxins leading to food poisoning, enterocolitis, epidermal necrolysis, TSS, and necrotizing pneumonia
– VIRULENCE: adhesions to bind and penetrate, enzymes for tissue breakdown, cytolytic toxins, and superantigens
Superantigens
inappropriately activate T cells and likely contribute to shock
Panton-Valentine Leukocidin (PVL)
A cytotoxin found in most strains of CA-MRSA. It creates pores in the membranes of cells surrounding infection and destroys invading leukocytes. Necrotic lesions of skin and mucosa
– Gene acquired from bacteriophage (lysogenic)
Three ways for bacteria to initiate infection
1.) breach the skin
2.) Systemic disease (lung–> skin)
3.) Toxin-mediated damage (wound–> toxin–> bigger wound)
Skin defenses
1.) Dry outmost protective layer
2.) antimicrobial peptides produced by epithelial cells
3.) Low pH of sebum
4.) Low pH and high salt content of sweat
5.) presence of lysozymes
6.) Langerhans cells (resident phagocytes) in epidermis
7.) competition with normal flora for resources on the skin
Acne/Folliculitis
Follicle-associated lesion.
propionibacterium acnes (G+, aerotolerant) in follicle–> releases lipase to digest surplus trapped oil –> lesion + local inflammation
Treatment: topical agents/ oral antibiotics
Imepetigo
Superficial bacterial infection that causes skin to flake/peel, honey colored crusts. Highly contagious, seen a lot in children.
Caused by: Staphylococcus aureus or Streptococcus pyogenes
Diagnosis: observation, topical mupirocin or oral cephalexin
Staphylococcus aureus
Bacteria, G(+), cocci clustered, Catalase(+), Coagulase(+), Uses protein A, coagulase, and hemolysins/leukocidins
Superficial (boils) and deep (furuncle/carbuncle). Common in surgical wounds. Seen in TSS, and scalded skin syndrome (ET-A and ET-B)
Staphylococcus Aureus virulence factors
1.) Hyaluronidase (breaks down connective tissues)
2.) Staphylokinase (lyses formed clots)
3.) Lipase (breaks down fat)
Streptococcus pyogenes
Bacteria, G(+), cocci chains, Catalase(-), beta-hemolytic, bacitracin sensitive
Common in impetigo, erysipelas, cellulitis, TSS, necrotizing fasciitis. Strep, scarlett fever, pneumonia, glomerulonephritis, and rheumatic fever (Strep=glomneph + rheumatic, skin= only rheumatic)
Streptococcus pyogenes virulence factors
1.) streptokinase (converts plasminogen to plasmin)
2.) M protein (resists phagocytosis)
3.) Hyaluronidase (breaks down connective tissue)
4.) DNase (digests DNA)
5.) Streptolysin O (destroys RBCs)
6.) Streptolysin S (destroys WBCs)
~ encoded by lysogenized prophage
Catalase test
Differentiates between C(+) microccal and staphylococcal species from C(-) streptococcal species
– Catalase is an enzyme that breaks down hydrogen peroxide to O2 and H2O (C(+) = rapid release of oxygen bubbles)
Coagulase test
Differentiate between staphylococcus aureus (coag+) from other staphylococcus that are Coag- (ex. staph epidermidis)
–When mixed with plasma, Coag+ will cause clumping or solid media
Novobiocin sensitivity
Differentiate between Staph saprophyticus (resistant) and Staph epidermidis (sensitive)
– Novobiocin inhibits bacterial DNA gyrase in susceptible (epidermidis) microorganisms
Cellulitis
Fast-spreading infection in the dermis and in the subcutaneous tissues. Pain, tenderness, and warmth on skin. Fever and swelling of lymph nodes draining the area,
–Most common cause in healthy people: Staph aureus, strep pyogenes. in infants: group B streptococci, occasionally from varicella
Staphylococcal scalded skin syndrome
Dermolytic condition caused by staph aureus, shedding occurs within the dermis. Most common in newborns and babies.
Gas gangrene
Caused by clostridium perfringens (anaerobic) that creates many exotoxins (ex. alpha-toxin). Spores of these species can be found in soil, human skin, and in the human intestine/vagina.
Treated with: penicillin and clindamycin
Clostridium perfringens
Bacteria, G(+), Bacilli, spore-forming, obligate anaerobe, only non-motile Clostridium member. Present in cellulitis (cracked skin), gas gangrene (myonecrosis with crepitus) (deep muscle lacerations), food poisoning
Treated with: surgical removal of infected areas. Hyperbaric oxygen to kill anaerobic organisms. Penicillin or clindamycin (only effective in local, weak infections)
Pseudomonas aeroginosa
Bacteria, G(-), bacilli, lactose non-fermenter, oxidase(+), glucose non-fermenter. “HOT TUB FOLLICULITIS”
–Comes from burn wound infection and folliculitis (hto water bacteria)
A vertical mattress suture is ideal for what kind of wound closure?
Both deep and superficial layers– good for gaping wounds
A horiztonal mattress suture is good for what kind of wound?
High tension wounds, and brittle skin (prevents tears)
Wound closure
Primary: Sutures, staples, tape, adhesives
Secondary: organic healing via the body
Contraindications for wound closure
- wound infection
- gross contamination
- infected tissue
- non-cosmetic wounds that come late to medical attention
- Animal bites
- Deep puncture wounds that cannot be irrigated properly
Time frame for sutures
Clean, uninfected lacerations on any part of the body in healthy patients: 18 hours
Facial wounds: 24+ hours
Wound management
Evaluate: Vascular, neuro, bleeding, healing expectation
Anesthesia: Local v digit v field block
Wound toilet: copiously irrigate
Wound closure: type and size
Complications of wound closures
Hypertrophic scars (keloids)
Wide scars (tension in collagen reformation)
Wound Dehiscence (non-adherence, wound splitting open)
Infection
Absorbable sutures
Gut, Chromic, Vicryl, Monocryl, PDS
Non-absorbable sutures
Prolene, Nylon, Stainless steel (bones/cartilage), Silk
Natural vs. synthetic
Natural: intense inflammation (ex. cow/sheep intestines, chromic/gut, silk)
Synthetic: less inflammation (ex. vicryl, monocryl, PDS, prolene, nylon)
Monofilament sutures
Appears as a single strand of suture material, minimal tissue trauma, ties smoothly, requires more knots, possesses memory (ex. monocryl, PDS, prolene, nylon)
Multifilament sutures
Fibers are twisted or braided together, greater resistance in tissue, fewer knots required (ex. vicryl, chromic, silk)
Suture size
zero is the reference size. More zeros is smaller
5-0 < 4-0 < 3-0 <2-0
Simple sutures
Simple interrupted stitches that are individually knotted, it used for uncomplicated laceration repairs and wound closures
Horizontal mattress sutures
Provides added strength, used in tough skin/calloused skin.
Two step stitch: simple stitch made, needle reversed and 2nd simple stitch made adjacent to first
Vertical mattress sutures
precise approximation of skin edges with eversion, provides additional strength to wound tension (for large gaping wounds)
Two step stitch: simple stitch made “far, far” relative to wound edge (large bite). needle reversed and 2nd stitch made inside first “near, near”
Arms and scalp sutures
4-0, for 7-10 days
Face sutures
5-0 or 6-0, for 3-5 days
Hands, feet, legs, trunk
3-0, 4-0, 5-0, for 10-14 days
Palms or soles
3-0, 4-0, for 14-21 days
Classical complement pathway
- Triggered by antigen binding to IgG (2) or IgM (pentamer)
- C1q, C1r2, C1s2
- Covalent attachment of C4b and C3b to surfaces via thioester bonds
- C4b2a is the C3 convertase
- C4b2a3b is the C5 convertase
MBL complement pathway
- Doesn’t require specific antibody, triggered by polysaccharide structure of microbes
- C1 independent formation of of the classical pathway C3 convertase (C4b2a)
- MBL –> MASP1 and MASP2 (like C1q –> C1r C1s in classical)
Alternative complement pathway
- Easily reactive to any foreign materials, LPS, and nucleophiles
- Oldest pathway
- Factor B and Factor D and properdin
- C3bBbC3b is the C5 convertase
- FB amplies C3bB binding
- FI, FH decays/inactivates C3b
C3 convertases
Classical: C4b2a
MBL: C4b2a
Alternative: C3bBb
C5 convertase
Classical: C4b2aC3b
MBL: C4b2a3b
Alternative: C3bBbC3b
Terminal lytic pathway
Occurs after the binding of C5b, 6, 7, 8, 9
- 9 is not required but the lysis will be SLOW without it
- osmolysis by puncturing a hole in the cell membrane
S protein in the fluid phase
C5b-9 may bind S protein in fluid phase (unattached), inhibiting lysis
Regulators of complement activation in plasma
Classical pathway: C1 INH, C4BP (no cleavage of C4)
Alternative pathway: Factor H (C3bBb inhibitor)
Membrane attack complex: S protein (inhibitor, binds C5b-7 and blocks its integration into membranes)
Membrane bound regulators of Complement activation
C3 convertase: CD46 cofactor activator
C3 convertase: CD55 decays acceleration
membrane attack complex: CD59, inhibitor of C9 (on your cells)
Factor H
A fluid phase inhibitor of alternative pathway C3 convertase. It binds C3bBb and dissociates the Bb. “decay acceleration of convertase” creates iC3b
- Also a cofactor for cleavage of C3b by Factor I
Things C4b and C3b can do
1.) Participate in continued pathway activation leading to MAC
2.) interact with CR1 –> opsonization clearance of immune complex
3.) degrades into fragments –> interacts with CR2 and CR3 –> opsonization clearance of immune complex
4.) augmentation of humoral immunity (x100)
Interaction with complement receptors
C3b: CR1 –> Clearance of immune complex
iC3b: CR1, CR2, CR3 –> Clearance of immune complex
C3d: CR2 –> Augment humoral immunity
CR1 (CD35) activity
Major ligands: C3b, C4b
- RBCs, WBCs, T cells, B cells
- transport immune complexes by RBC
- promotes immune adherence (opsonized)
- promotes phagocytosis with Fc receptors
- Blocks formation of C3 convertase
Binding of C3b to the Ab:ag complex
interferes with lattice formation, limiting its growth and keeps Ab:ag complexes soluble
Immune complex transport
Major mechanism for removal of ICs. ICs coated with C3b bind to CR1 (on RBC) and transport them to the spleen/liver/etc for clearance via macrophages
CR2 (CD21/CD19/CD81)
Major ligands: C3d, C3dg, iC3b
- B CELLS, follicular DC, some T cells
- B cell co-receptor, bind EBV
- augments stimulation of the B cell to increase humoral immune response
CR3 (CD11b/CD18)
CR4 (CD11c/CD18)
Major ligand: iC3b
- Cell adhesion binds immune complex
- monocytes, macrophages, neutrophils, NK, T cells
What are the anaphylatoxins
GPCRs (7-transmembrane proteins)
C3a and C5a via C3a receptor, C5a receptor, respectively
– potent inflammation causers: Chemotaxis, smooth muscle contraction, increased vascular permeability, degranulation of mast cells, neutrophil activation
C1, C2, C4 deficiency
Immune-complex disease
C3 deficiency
Susceptibility to encapsulated bacteria
C5-C9 deficiency
Susceptibility to Neisseria (meningitis)
Factor D, prosperdin (Factor P) deficiency
Susceptibility to encapsulated bacteria and Neisseria but NO immune-complex disease
Factor I deficiency
Similar effects to deficiency of C3
Immune complex Disease
– Type III hypersensitivity
– Ex. Lupus (SLE), Rheumatoid arthritis, glomerulonephritis
Complement deficiencies
–increase IC or autoimmune disease (Classical pathway or C3 deficiencies)
– Infections (Classic, alt, MBL pathways)
– Neisseria infections (alt pathway and terminal lytic)
aHUS (atypical hemolytic uremic syndrome)
MCP (CD46), Factor I, Factor H, C3, Factor B
damage to platelets, RBCs, and kidney inflammation. Leads to systemic thrombotic microangiopathy. Blood clot disorder in small vessels from overstimulation of the alternate pathway
Age-related macular degeneration (eye)
Polymorphisms in factor H
Autoimmune-like conditions, including paroxysmal nocturnal hemoglobinuria
DAF, CD59, CD55
Hereditary angioedema (HAE)
C1 INH
– Reccurent episodes of localized edema in skin, GI tract, or larynx
– C1 inhibitor inhibits C1 esterase (too much activation) –> leads to over consumption –> C4, C2
– Also inhibits MASP, kallikrein, plasmin, Factor XIa, Factor XIIa, and bradykinin B2 receptor
Paroxysmal nocturnal hemoglobinuria
Deficiency on CD55 and CD59
Treatment for C1 INH
– Anabolic steroids to increase synthesis of C1 INH
– Purified C1INH (but expensive)
– Kallikrein inhibitors and bradykinin B2 receptor inhibitors (excess kinin formation responsible for the episodes of edema)
DAF (CD55 and CD59) deficiency and treatment
DAF: in a post-translational modification of the peptide anchors that bind the proteins to the cell membrane
– increased susceptibility of erythrocytes to MAC-mediated lysis (PNH, RBC osmolysis)
Treatment: antibody to C5 (eculizumab) reduces hemolysis (HOWEVER: inhibiting C5 can lead to susceptibility to neisseria infections)
Superficial fungal skin infections
- Pityriasis versicolor
- Tinea nigra (tinea= gnawing worm or moth)
Cutaneous fungal skin infections
Dermatophytosis (other Tineas)
Subcutaneous fungal skin infections
- Sporotrichosis
- Chromoblastomycosis
~ RARE
Cutaneous/systemic fungal skin infections
- Candidiasis
- Cryptococcosis
- Blastomycosis
Pityriasis (tinea) versicolor
Malassezia furfur
- epidermal infections on the back, chest, neck, and upper arms. Painless but may itch, scaling, and can recur easily
- spaghetti and meatballs (spores and hyphae)
- Diagnosis by KOH mount/prep of skin scraping
Tinea Nigra
Exophiala werneckii (Hortaea werneckii)
- Tropical infection. Florida, North, South Carolina
- Dark brown/black patches on the soles of the hands or feet. Irregularly shaped but well circumscribed, fine scale, painless, generally does not recur (long time to clear)
- Diagnosis by KOH mount/prep of skin scraping. Expect to see hyphae that are thick, irregular, and have a slight color
Effective treatment for Pityriasis versicolor and Tinea nigra
- application of dandruff shampoo containing selenium sulfide
- topical antifungals
~ Skin discoloration will take longer to resolve in pityriasis versicolor compared to the M. furfur infection
Dermatophytoses
Trichophyton- most common in USA (microsporum, epidermophyton)
- Lives on you dead stuff
- Secrete keratinase (digests keratin, hair, skin, nails)
- Warm + moist skin = occurrence and recurrence
Ringworm
Tinea corporis (body) dermatophytoses cutaneous infection
- itchy red rash presents on the trunk/extremities
- Centrifugally from a core, leaving a central clearing
- expanding raised red border, scaling
- common in children
Jock itch
Tinea Cruris (groin) dermatophytoses cutaneous infection
- itchy red rash extending anywhere from the groin, upper thigh, and perineum to the perianal region
- Similar pattern to tinea corporis
- common in children
Athlete’s foot
Tinea pedis (feet) dermatophytoses cutaneous infection
- Trichophyton rubrum
- common in adults rather than children
- co-present with onychomycosis
Scalp ringworm
Tinea capitis (scalp) dermatophytoses cutaneous infection
- Trichophyton tonsurans
- Male, urban, african decent
- 5-10 year olds, very transmissible
Onychomycosis
Tinea unguium (nail) dermatophytoses cutaneous infection
- Trichophyton rubrum
- Clinical signs resemble psoriasis
Acute: spongiosis, acanthosis, pappillomatosis with edema, and hyperkeratosis
Chronic: nail bed = hyperkeratotic, thickened, nail detaches or becomes distorted
Candidiasis
Candida albicans
- skin, mouth, GI tract
- YEAST, pseudohyphal form
- diaper rash, skin folds, oral thrush, vulvovaginal
Diaper rash
Candida albicans: initiates with irritant dermatitis
fecal bacteria –> urease –> urea in urine –> increased pH –> overgrowth of c. albicans
Sporotrichosis
Caused by sporothrix schenckii on soil and plants
- rose gardner’s disease
-Dimorphic: 37C=yeast that buds, 25C=hyphae
- cultured on Sabouraud SDA
Chromoblastomycosis
- Neglected tropical disease, rare in USA
- initiates with skin puncture, cause by MELANIZED FUNGI
- wart-like appearance, then cauliflower-like, can lead to tissue fibrosis and lymphedema that leads to disability
- diagnosed by ID muriform cells (Medlar/sclerotic bodies) in KOH prep or biopsy
Systemic fungal infections that can include a skin presentation
1.) Blastomycosis (Mississippi river valley), repiratory transmission of BLASTOMYCES DERMATITIDIS, skin ulcers can form
2.) Cryptococcosis, mainly in immunocompromised pops, resp. transmission by CRYPTOCOCCUS NEOFORMANS, skin lesions with acne-like appearance
Polyenes
bind to ergosterol, disrupt cell membrane in fungi
Azoles
inhibits CYP450 family lanosterol demethylase leading to loss of membrane ergosterol – targets ERG11
Allylamines
inhibits squalene oxidase in ergosterol biosynthesis, thus loss of membrane ergosterol
“Anti-metabolite”
inhibits DNA synthesis but also likely affects RNA and protein synthesis
Polyenes: Amphotericin B
IV, against Candida broad spectrum
Liposomal (Ambisome) 1 molecule amphotericin B coated with 9 lipid molcules = movement help
-relatively toxic (amphoterrible/awfultericin)
Polyenes: Nystatin
Topical, targets: candida albicans (cutaneous)
too toxic for systemic use
Azoles: Clotrimazole and miconazole (imidazoles)
Topical, targats: c. albicans, (cutaneous), Mala. furfur, exophiala werneckii, dermatophytes topically reached
too toxic for systemic use
Polyenes: Nyastatin
Oral suspension (not absorbed), targets c. albicans in oral thrush
not absorbed by GI tract
Azoles: Clotrimazole
Troches and suppositories, targets c. albicans for thrush and vaginitis, respectively
Azoles: Fluconazole (triazole)
Oral and IV, targets c. albicans, cryptococcus neoformans, and systemic fungal infections
Main azole used for systemic infections, fewer off-target effects
(also included: itra, vori, posa, isavu-conazole)
Azoles: others
Oral and IV, have broad activity, systematic fungal infection use
issues w toxicity: itroconazole for phialophora and cladosporium species causing chromoblastomycosis
Allylamines: Terbinafine
Oral: dermatophyte infection of the nails, scalp, and ones refractory to topical treatments – treatment accumulates in nails
Topical: dermatophyte infections of the skin
“Anti-metabolite”: Flucytosine
IV, targets cryptococcus and c. albicans. Good for CNS crossover, meningitis
Rarely used alone, resistance develops quickly
Glucan Synthesis inhibitors (echinocandins): Caspofungin, micafungin, and anidulafungin
IV, targets ALL candida species, Aspergillis as a last resort
Griseofulvin
Oral, Targets dematophyte infections of the scalp in children (and nail infections). Also for other dermatophyte infections that are refractory to topicals
Static rather than cidal, works very slowly
Potassium iodide
Oral, targets sporothrix schenckii by unknown mechanism
Contraindicated for: pregnancy, hypersensitivity to iodide, acute bronchitis, and TB
Folate inhibitors: TMP/SMX
Oral, targets pneumocystis jirovecii (which causes pneumo. pneumonia in AIDS)
Common antibacterial
Systemic fungal infection drugs
1.) Amphotericin B - IV
2.) Flucytosine - oral
3.) Echinocandins - IV
4.) Azoles - oral or IV - broad spectrum
Cutaneous or subcutaneous fungal infection drugs
1.) Topical imidazoles for SKIN ONLY
2.) Terbinafines (oral) and some azoles (oral) for nail/scalp dermatophytes
3.) Griseofulvin (oral) for tinea capitis
Superficial fungal infection drugs
1.) Selenium sulfide containing shampoo
2.) imidazoles- topical
Oral thrush drugs
Nystatin + Clotrimazole troches (lozenge) - swish and swallow
Candida vaginitis drugs
clotrimazole suppositories
Sporotrichosis drugs
potassium iodide (unless systemic) – pot plants (roses) get sporotrichosis
Chromoblastomycosis drugs
oral itroconazole and local excision (severe disease can be refractory to treatment)
Oculocutaneous Albinism
OCA
- melanocyte amount normal– don’t produce melanosomes because of a tyrosinase enzyme dysfunction
- skin, hair, eyes
- Reduces visual acuity and photophobia
- nystagmus, strabismus, lack of binocular vision
OCA1
Most severe, complete lack of tyrosinase from gen mutation, 40% of cases
OCA2
P gene mutations, altered trafficking of tyrosinase, 50% cases (most common)
OCA3
Tyrosine-related protein1 (TYRP1) gene mutations, maintenance of melanosomes, cannot stabilize tyrosinase
OCA clinical course and treatment
Varies according to type and amount of melanin present
• OCA2 1000x increased risk of squamous cell carcinoma
• treatment includes prevention of complications and psychosocial support
Vitiligo
Multifactorial disorder leading to the auto immune destruction of melanocytes
Clinical presentation: macules or patches surrounded by normal skin, centrifugal enlargement at variable rates, other immune disorders sometimes present
Vitiligo treatment
Topical steroids: don’t work very well
Narrowband ultraviolet B therapy: prolonged treatment
Melasma, mask of pregnancy
•Increased facial pigmentation
• 90% of cases are women
• Symmetric patches with irregular borders
• increased pigment in epidermis and or dermis with normal or minimally increased number of melanocytes
Post inflammatory hyperpigmentation
Excess melanin pigment following cutaneous inflammation or injury. More frequent, severe, and longer duration in those with dark skin. Distribution and history are key to recognition

Post inflammatory hyperpigmentation pathogenesis
Epidermal: increased melanin produced and transferred to keratinocytes
Dermal: damage basement membrane leads to melanosomes deposition in dermis and phagocytosis by macrophages
Ephelis (freckles)
Most common pigmented lesion of childhood in lightly pigmented individuals. Increased pigment in basil keratinocytes, little or no increase in melanocytes
Café au lait macules
Well circumscribed, uniformly pigmented macules or patches
Consider NF one, and McCune Albright syndrome for genetic disorders associated with these
Lentigo Simplex and mucosal melanotic lesions
Brown macule was an early age of onset. Oral and genital forms are common.
Pathology: elongated rete ridges with hyperpigmented bases and increased density of melanocytes
Management: often biopsied due to concerns for melanoma
Dermal melanocytosis
Very common pigmented blue to blue/gray patch more common and darker skin. Present at birth, fades during childhood
• Lumbosacral: many spots here (Regression of melanocytes happens slowest here in embryology)
• Nevus of ito: shoulder/clavicular area
• nevus of ota: Eye, sclera color present at birth, persists through life
Blue nevus
• Acquired during childhood
• sacral, scalp, dorsal distal extremities
• Small blue gray or blue black papules
• Heavily pigmented spindle-shaped melanocytes and Lana stages in the dermis
• Often biopsy due to concern for melanoma
Common acquired melanocytic nevi (moles) 
Well circumscribed, symmetric, round to oval lesions 2 to 6 mm diameter
Oncogenes: NRAS and BRAF present
Three pathologies:
1.) Junctional nevus (epidermal)
2.) Compound nevus (both)
3.) Dermal/intradermal nevus (dermal)

Atypical (dysplastic) nevi
• possible direct precursor to melanoma
• 50% probability of melanoma by age 60
• CDKN2A and CDK4
• Larger than ordinary nevi, but many
• Sun exposed and protective surfaces
Severe atypia
Re-excise with 5 mm margin and pathologic confirmation of complete excision (Treat like melanoma in situ) 
Melanoma
• malignant neoplasm of melanocytes
• Most lethal skin cancer
• Acquired by UV/sun exposure
• BRAF mutations are common
• V600E mutation has a targeted therapy 
Tool for recognizing melanoma
A -Asymmetry
B -Border irregularity
C -Color variation
D -Diameter > 6 mm
E - Evolving overtime
Melanoma in situ MIS
Malignant melanocytes only within epidermis
Lentigo maligna
MIS on sun damaged skin, usually face
Melanoma
Malignant melanocytes in epidermis and dermis
Lentigo maligna melanoma
Melanoma arising in lentigo maligna
Acral lentiginous melanoma
• elderly patients, 5% of melanoma
• Palms, soles, around nail apparatus
• Longitudinal melanonychia: pigmented nail bands
Melanoma tumor staging
PTis < pT1 < pT2 < pT3 < pT4
• going from in situ to increasing thickness
Melanocytic lesions or sampled by:
Punch biopsies or excision procedures
— Do you want clinical margin to be 5 mm or greater, and pathologic margin to be negative
Pyogenic granuloma/lobular capillary hemangioma
• rapidly growing, friable, red papule or polyp, skin or mucosa, frequently ulcerates
• Children, young adults, gingiva of pregnant women
Cherry hemangioma
• Bright red, dome shaped to polypoid papules, minute up to several mm
• Trunk and upper extremities, elderly adults may have many on their trunk
Venous Lake
• benign dark color, blanches with pressure
• Ears, lips most common
• Only excised for cosmetic concern or prone to repeat bleeding
Spider angioma
• Benign but suggestive of underlying systemic disease such as cirrhosis, rheumatoid arthritis, or thyrotoxicosis
• Multiple or characteristic of chronic liver disease
• solitary lesions are common in young adults, appears in pregnancy
Solar lentigo
• very common tanto brown macule related to chronic UV exposure
• Epidermal hyperplasia, present on over 90% of Caucasians over the age of 60
• “ Liver spots” 
Seborrheic keratosis
• Common benign lesion appearing in people older than 40
• stuck on appearance, variable pigment
• Horn cysts from hyperkeratosis
Dermatosis papulosa nigra
• most common in African dissent with darkly pigmented skin
• Multiple hyperpigmented papules on the face
• Normal skin
Acanthosis Nigricans
• thickened, hyperpigmented skin with velvet like texture in flexural areas
• Associated with obesity, diabetes, cancer, increased growth factor receptor signaling
Fibroepithelial polyp, acrochordon, skin tag
• very common, middle age and older, neck, trunk, face, intertriginous 
• can be associated with obesity, pregnancy, diabetes (Hormonal changes)
Actinic keratosis
• early step in squamous cell dysplasia to carcinoma sequence
• Rough lesions, site of moderate sun damage, hyperkeratosis, basal cell atypia, TP53 mutation
• Gray macules and cutaneous horns
Treatment of actinic keratosis
• local eradication by cryotherapy or field therapy (Including 5FU topical, imiquimod- activates TLRs, or photodynamic therapy)
Squamous cell carcinoma
• invasive malignant neoplasm of keratinocytes
• Red scaling plaques to nodular ulcerated lesions. Contains intercellular bridges (spaces w desmosomes still attached between cells)
• Caused by sun exposure, chronic inflammation, immunosuppression, arsenic exposure
Basal cell carcinoma
• Most common invasive cancer in humans
• Sun exposed, elderly
•  pearly papules with prominent shallow blood vessels (Subepidermal/telangiectasia)
• Sometimes ulcerated lesions with rolled up pearly borders
Pathogenesis of basal cell carcinoma
• uncontrolled hedgehog and patch signaling
• Tumor cells resemble normal basal layer of epidermis, but have a cleft surrounding edges of tumor nests
Superficial basal cell carcinoma
• Well circumscribed, erythematous, macule/patch or thin papule/plaque
• superficial multifocal
Nodular basal cell carcinoma
• shiny, pearly PapiWall or nodule with a smooth surface and arborizing telangiectasias
• complete excision required
Morpheaform Basal cell carcinoma
• more aggressive tumors, requiring complete excision, Mohs surgery
• Light pink to white with ill defined borders, May resemble a scar
Treatment of squamous cell and basal cell carcinomas
• local surgery complete excision (BCC and SCC)
•  Curettage with electrodesiccation (BCC or small SCCin situ)
•  medical treatment, 5FU (Superficial or in situ BCC & SCC)
Merkel cell carcinoma
• oncology required, primary neural endocrine carcinoma of the skin PNECS
• Head, neck, butt
• Pink red, firm, dome shaped, solitary module that has grown rapidly
• aggressive tumor with significant risk for recurrence and death
Merkel cell carcinoma pathogenesis
• Stains with cytokeratin 20
• localized in the basal layer of the epidermis
• Merkel cell Polyomavirus infects 80% of these tumors, the other 20% that are virus negative have multiple UV signature mutations

Vesicular or pustular rash diseases
• herpes simplex virus 1
• Herpes simplex virus 2
• Varicella zoster virus
• Coxsackieviruses A and B
• smallpox
• Orf virus
Maculopapular rash diseases
• measles
• Rubella
• Parvovirus B19
• Roseolovirus (HHV-6 and -7)
• Epstein bar virus (HBV or HHV-4)
• Echo virus
• West Nile virus
Wart like eruption diseases
• papules
• human papillomavirus
• Molluscum contagiosum
Herpesvirus descriptor
Linear genome, class one, dsDNA, envelope, tegument protein, spike protein, icosahedral protein capsule
• Alpha, beta, gamma
Alpha herpes viruses
Herpes simplex one (HSV-1), herpes Symplex two (HSV-2), and varicella zoster virus (VZV)
— Neuron latency
Beta herpes viruses
Human cytomegalovirus (HCMV, HHV-6, HHV-7)
— Immune cells latency
Gamma herpes viruses
Epstein-Barr virus (EBV), Kaposi sarcoma associated herpes virus (KSHV)
— B cell latency
Herpes simplex 1 (HSV1)
• Alpha herpesvirus
• HHV1
• causes: Gingivostomatitis, keratoconjunctivitis, herpes labialis, temporal lobe encephalitis
Herpes simplex 2 (HS2)
• alpha herpes virus
• HHV2
• causes: genital herpes or neonatal herpes
Varicella zoster virus (VZV)
• alpha herpes virus
• HHV3
• causes: Chickenpox and shingles
• spreads through airborne, close contact
Human cytomegalovirus (CMV)
• beta herpes virus
• HHV5
• causes: Congenital Cytomegalovirus infection, systemic infection, mono like infections
Roseoloviruses
• beta herpes virus
• HHV6A/B and HHV7 
• causes: Exanthem subitum (sixth disease), Encephalitis in immunocompromised
Epstein bar virus (EBV)
• gamma herpes virus
• HHV4
• Mononucleosis, lymphoid organ related cancers
Kaposi sarcoma associated herpes virus (KSHV)
• Gamma herpes virus
• HHV8
• causes: Kaposi’s sarcoma
Poxviruses
• dsDNA, group I
• linear genome, complex nucleocapsid, enveloped
• includes: molluscum contagiosum, smallpox, and orf virus
• rash, fever, respiratory, T cell and B cell response
Picornaviruses
• enterovirus
• IgA secreted to fight
• ssRNA (+), group IV
• Non-segmented, icosahedral nucleocapsid, non-enveloped
• includes hand-foot-mouth and echovirus (and rhino/polio/entero)
1.) Measles virus (Rubeola)
• ssRNA(-), group V
• non-segmented, helical nucleocapsid, enveloped, paramyxoviridae, morbillivirus
• Complications include: otitis media, group, bronchopneumonia, encephalitis, SSPE
3.) Rubella virus
• ssRNA(+), group IV
• non-segmented, icosahedral nucleocapsid, enveloped, togaviridae, rubivirus
• adult: pain in joints wrists, fingers, knees. More common in women. Can lead to congenital defects for babies in pregnant women
5.) Fifth disease, erythema infectiosum, parvovirus B19
• ssDNA, group II
• linear genome, icosahedral nucleocapsid, non-enveloped, parvoviridae
• slapped cheek appearance
•  Aplastic crisis in patients with chronic hemolytic anemia 
6.) sixth disease - Roseola 
• occurs in young children and babies
•  very high fevers, rash on chest and trunk
• Mononucleosis-like or hepatitis-like symptoms in adults
• potentially treated with gancyclovir
• Dangerous for people with AIDS 
human papillomavirus (HPV)
• ddDNA, group I
• Circular genome, icosahedral nucleocapsid, nonenveloped, papoviridae
• infects epithelial cells of skin, mucous membranes
• Blocks p53 and E2F, which is carcinogenic
• test with Pap smear for cervical cancer (Large cells with large nuclei or binuclei indicates cancer) — PCR-based screening tests
HIV fusion inhibitors
- Enfuvirtide (locks GP41 I belonged state)
- Maraviroc (used when CCR5 coreceptor is used
HIV integrase inhibitors
- Dolutegravir
- Elvitegravir
- Raltegravir
• Inhibit HIV genome integration into the host cell chromosome by reversibly inhibiting the HIV integrase enzyme
HIV reverse transcriptase inhibitors NRTIs
- Abacavir
- Didanosine
- Emtricitabine
- Lamivudine
- Stavudine
- Tenofovir (nucleotide)
- Zidovudine
• competitively inhibit nucleotide binding to reverse transcriptase and terminate the growing DNA chain (Missing 3’ OH group, trick nucleotide)
NRTIs side effects
• bone marrow suppression (reversed with G-CSF, and erythropoietin)
• Peripheral neuropathy, lactic acidosis, pancreatitis
HIV reverse transcriptase inhibitors NNRTIs 
- Delavirdine
- Efavirenz (not in pregnancy)
- Nevairapine
• Block active site of reverse transcriptase enzyme, lose enzyme function
• do not require phosphorylation to be active (Unlike NRTIs)
• Compete with nucleotides
HIV protease inhibitors
- Atazanavir
- Darunavir
- Fosamprenavir
- Indinavir
- Lopinavir
- Ritonavir (inhibits CYP450 too)
- Saquinavir
• protease inhibitors block the function of polypeptide cleavage, preventing the maturation of new viruses
Interferon-a
• type I IFN, glycoprotein that is normally synthesized by virus infected cells that exhibit a wide range of antiviral properties
• Used in treatment of chronic HBV and HCV, KSHV, hairy cell leukemia, condyloma acuminatum, Renal cell carcinoma, and malignant melanoma
SE: Flu like symptoms, depression, neutropenia, myopathy
Nucleic acid synthesis inhibitors
- Acyclovir (Used against HSV, VZV, EBV)
- Ganciclovir (Used against CMV)
• Guanosine analogues— Not monophosphorylated in non-infected cells, only in HSV or VZV encoded thymidine kinases
Nucleic acid synthesis inhibitors— Viral DNA polymerase inhibitors
- Cidofovir (HSV-acyclovir resistant, CMV)
- Foscarnet (HSV-acyclovir resistant, and CMV-ganciclyovir resistant)
• nephrotoxic, not first-line drugs
Nucleic acid synthesis inhibitors— Guanine nucleotide synthesis inhibitor
- Ribavirin (RSV, HCV)
- inhibits the synthesis of guanine nucleotides by competitively inhibiting inosine monophosphate dehydrogenase
- causes hemolytic anemia, is a teratogen
Viral release inhibitors
- Oseltamivir (Flu A and B)
- Zanamivir (Flu A and B)
- inhibit the influenza neuraminidase enzyme which results in a decreased release of progeny virus particles— Must be used early to be effective
- Enzyme Cleves away salicylic acid from binding to hemagglutinin, locks viruses into the host that is dying
Rate limiting step to topical therapy absorption
Stratum corneum, brick and mortar barrier for the skin
Two important mechanisms for absorption
Hydration: str. corneum more penetrable
Vehicle: determines occlusivity and absorption (lipid vs. water)
Corticosteroids
- anti-inflammatory, immunosupressive, anti-proliferative, vasoconstrictive
Uses: eczema, contact dermatitis, psoriasis, itch, lichen planus
Adverse effects of corticosteroids
skin atrophy (transparency occurs), striae (stretch marks), acne. suppression of the HPA axis
Corticosteroid strength
1- strongest, usually ointment, hands/feet
7- weakest, usually cream, babies and facial skin
Topical Retinoids
Vitamin A analogs which work through nuclear receptors in the DNA causing alteration of gene transcription (cellular differentiation)
Examples: tretinoin (Retin-A), tazarotene (Tazorac), adapalene (Differin gel)
Topical retinoids actions/uses/AE
Actions: Regulate cell growth, inhibit carcinogenesis, alter enzymes involved with cellular differentiation(maturation)
Uses: acne, psoriasis, cosmetic skin improvements
AE: dryness, irritation, sun sensitivity
Calcipotriene (Dovonex)
A vitamin D analog that acts through DNA receptors to alter skin differentiation (through nucleus, non-steroid alt)
Uses: psoriasis, eczema
AE: irritation, increased serum calcium
Topical Calcineurin Inhibitors: TCIs
Tacrolimus (Protopic), pimicrolimus (Elidel)
– acts through calcineurin (a protein phosphatase) to alter T cell activation
AE: limited action, local irritation/burning
Crisaborole (Eucrisa) ointment
Well-tolerated, newer medication for Atopic dermatitis
Mech: inhibits PDE4 (phosphodiesterase-4) which reduces production of pro-inflammatory cytokines
Mohs micrographic surgery
excision of cancer from the skin, fresh frozen prep onto slides, reading of slides by surgeon to evaluate margins (while cut still open– chance to go back and get missing tumor)
Sunscreens
UVA: 320-400, reach dermis
UVB: 290-320, reach epidermal base (burn, cancer)
Avobenzone/helioplex/mexoryl= UVA protectors
Titanium dioxide/zinc oxide= reflectors
SPF– Sun protection factor
indicated relative sun protection from a given product against UVB
- SPF 2= 50%
- SPF 15= 93%
- SPF 30= 97%
Imiquimod cream (aldera)
– Immune response modifier (increases response via TLR-7 activation, INF, TNF, NK cells, T cells
Uses: condyloma (genital warts), Actinic keratosis, BCC
occasionally used for: common warts, molluscum, in situ Ca, in situ melanoma
Topical 5-FU (Carac, Efudex)
Inhibits thymidylate synthase resulting in reduced DNA synthesis
- acts selectively in actinic keratosis damaged skin cells (cells with high turnover rates)
Systemic retinoids
Isotretinoin: Accutane
Acitretin: Soriatane
– Vitamin A analogs that bind to the nuclear retionoid receptors to alter gene transcription and “normalize” cell differentiation
USES: acne, psoriasis, ichthyosis, Darier’s disease, chemoprophylaxis of skin cancer – repairs disordered keratinization
Adverse effects of systemic retinoids
Dryness, hyperlipidemia, teratogenicity, hepatitis, hair loss, arthralgias, pseudotumor cerebri, headaches, DISH, depression
Labs run: Lipids, LFT, HCG
Dapsone Oral medication
-Sulfone, sulfa meds
-Mainstay leprosy therapy
ACTION: inhibits myeloperoxidase in NEUTROPHILS (CD11a/CD18)
USES: dermatitis herpetiformis, linear IgA disease, bullous lupus, Sweet’s syndrome, spider bite
Methotrexate
Action: dihydrofolate reductase inhibitor that disrupts DNA synthesis to block cell division (immunosuppressive)
Uses: psoriasis, CTCL, lupus
AE: Hepatotoxicity, myelosupression, pneumonitis
Biological therapies
Biogenetically engineered proteins which disrupt/inhibit focused portions of the immune system involved in psoriasis (and other diseases). Targets signal molecules and immune cells
Dupilumab (Dupixent) injection
Biologic therapy for mod-to-severe atopic dermatitis. Inhibits IL-4, IL-13 involved in B and T cell activation and stimulation of humoral immunity including IgE
Ultraviolet light therapy
- Narrow band UVB (311nm)
- PUVA (psoralen plus UVA light at 320-400nm)
- Forms pyrimidine dimers in DNA and reduces langerhans cells and leukocytes. Anti-inflammatory/immunosupressive
USES: psoriasis, pruritus, eczema, CTCL
AE: burns, carcinogenic, photo-aging
Minoxidil (2% or 5%)
Rogaine (topical foam 2x a day)
- vasodilation and direct stimulation of hair shaft growth
- used for alopecia
Finasteride (1mg)
Propecia
- blocks 5-alpha reductase enzyme in follicles to inhibit the conversion of testosterone to dihydrotesterone
USES: androgenetic alopecia (pattern baldness)
Liquid nitrogen
- Freezes/kills tissue
USES: warts, actinic keratosis, irritated keratosis, skin tags, skin cancer - 3-5 seconds for AK
- 10-15 seconds for warts
- 20-30 seconds for skin cancers
Stages of hair cycle
Anagen (growth) –> Catagen (transition) –> telogen (rest/shed)
Androgenetic alopecia
-Simple baldness, hereditary alopecia, pattern alopecia
-non-scarring
- miniaturization of hair follicles triggered by androgens
Treatments: Minoxidil, finasteride, hair transplants
Telogen Effluvium
- Stress hair loss
- disrupted growth cycle of hairs causing premature shift from anagen –> telogen
Treatments: Minoxidil, remove trigger, time
Alopecia Areata
Autoimmune disorder of hair loss where T-cells attack the hair bulb, HLA determined (immune epitope present)
- A. totalis (scalp) and A. universalis (all body)
Treatment: Topical or IL steroids, minoxidil, anthralin/SADBE, JAK inhibitors (effective)
Secondary alopecia
Diffuse hair thinning as a complication of an existing medication or medical problem
From: chemo, meds, hepatic failure, nutritional disorder, etc
Treatment: remove cause/trigger, minoxidil
Pediculosis (Lice)
Head: pediculus humanus capitis
Body: pediculus humanus humanus
Pubic: Pthirus pubis (crabs)
Paronychia
Inflammation of the nail folds
ACUTE: trauma, bacteria, contact derm., eczema falir
CHRONIC: irritant contact derm., eczema, psoriasis, cadida albicans
