- Well-circumscribed change in skin color

- Not elevated or depressed

- Less than 1 cm in diameter

- Non-palpable on exam

- Non-inflammatory

- Examples: Vitiligo, lentigines, ochronosis, melasma, port-wine stain, petechiae, and ecchymosis

- Circumscribed change in skin color

- Not elevated or depressed

- Greater than 1 cm in diameter

- Not palpable on exam

- Non-inflammatory

- Examples: Vitiligo, nevus spilus, nevus anemicus, purpura, and notalgia paresthetica

- Well-circumscribed solid elevations of the skin

- Not fluid filled

- Less than 1 cm in diameter

- Domed, flat-topped, and umbilicated

- Examples: Lichen planus, guttate psoriasis, leukocytoclastic vasculitis, melanocytic nevus, molluscum contagiosum, morbilliform drug eruption, and polymorphous light eruption

- Something either inflammation or neoplasm fills part of the dermis causing elevation

- Broad papule or confluence of papules

- More than 1 cm in diameter

- Typically flat-topped but may be centrally depressed

- Examples: Psoriasis, Eczematous dermatitis, Lupus erythematosus, Dermatomyositis, Mycosis fungoides, and Sarcoidosis

- Swelling of the skin

- Characterisitically evanescent and disappears within hours

- Borders of a wheal are not stable and move from involved to adjacent uninvolve areas over hours

- Pink to pale red in color

- May be tiny papules 2-4 mm in diameter or giant plaques measuring greater than 10 cm

- Variable shapes

- Morphologically similar to papules

- More than 1 cm in diameter

- Roundish rather than broad and flat

- Frequently centered in the dermis or subcutis

- Examples: Cutaneous lymphoma, cutaneous carcinoma (basal cell or Merkel cell), metastasis, erythema nodosum, polyarteritis nodosa, and infectious abcesses

- Soft or firm movable or fixed masses

- Variable size but usually greater than 2 cm

- Roundish

- Implies neoplasm

- Fluid-filled epidermal elevations

- 1-10 mm in size

- Sometimes in clusters

- May be filled with a serous exudate or blood

- Larger version of a vesicle

- Greater than 1 cm in diameter

- Examples: Bullous impetigo, herpes simplex, allergic contact dermatitis, bullous pemphigoid, arthropod bite reaction, and porphyrias

- Small elevations of the skin containing purulent material

- Typically caused by necrotic inflammatory cells --> Neutrophils

- Similar to vesicles in shape

- Inflammatory halo

- Examples: Bacterial folliculitis, acne vulgaris, acute generalized exanthematous pustulosis, pustular psoriasis, and tinea faceii

- Deep necrotizing folliculitis with suppuration

- Presents as an inflammed follicle centered nodule

- Greater than 1 cm with overlying pustule

- Carbuncle: Several furuncles coalescing

- Localized accumulation of purulent material

- Pus usually not visible due to material being so deep in the dermis or subcutaneous tissue

- Examples: Infectious

- Excess stratum corneum accumulated in flakes or plates

- Becomes apparent when epidermal differentiation is disordered

- Accumulation and casting of stratum corneum becomes apparent as scale

- Ranges in size from fine dust like particles to extensive parchemnt like sheets

- Can also be a sign of malignancy --> Keratin accumulation in SCC

- Types: Crack-like, exfoliative, follicular, gritty, ichthyosiform, and keratotic

- Conical mass of cornified cells

- Arises over an abnormally differentiating epidermis

- Hair follicle infundibulum that is dilated and plugged by keratin and lipids

- Open comedo: Open pilosebaceous unit with visible keratinoceous plug

- Closed comedo: Follicular opening is unapparent and accumulates whitish keratin

- Hardened desposits that result when serum, blood or purulent exudate dries on the skin's surface

- Colors: Yellow-brown (serum), turbid yellowish-green (purulent), and reddish-black (blood)

- Small or punctuate crust may result from scratching

- Larger honey colored moist crusts form with impetiginization --> Secondary suppuration

- Linear or punctate surface excavations of epidermis

- Results from scratching

- Distributed over reachable areas

- Linear loss of continuity of the skin's surface or mucosa

- Results from excessive tension or decreased elasticity of tissue

- Frequently on palms and soles --> Thick stratum corneum is least expandable

- Transitional areas between skin and mucosa are susceptible

- Skin overlying joints are also susceptible

- Thickened skin with accentuated markings

- Resembles tree bark

- Induced by reapeated rubbing

- Diminution in the size of a cell, tissue, organ, or part of body

- Atropic epidermis: Glossy, almost transparent, paper thin, wrinkled, and may not retain normal skin lines

- Dermal atrophy: Decrease in papillary or dermal CT manifesting in depression of the skin

- Atrophy of panniculus results in more substantial depression of the skin

- Moist, circumscribed, depressed lesion

- Results a partial thickness loss of the epidermis

- Tends not to scar

- Defect in which the epidermis and papillary dermis are removed

- Tissues below papillary dermis may be involved too

- Breach of the dermis and destruction of adnexal structions 

- Breakdown impedes re-epithelialization

- Defect heals with scarring

- Location: Medial ankle or pressure points

- Borders: Rolled, undermined, punched out, jagged or angular

- Base: Clean, ragged, or necrotic

- Discharge: Purulent, granular, or malodorous

- Surrounding colors: Red, purple, pigmented, reticulated, indurated, sclerotic, or infarcted

- Thickening or thinning of the skin with fibrous tissue replacing normal tissue

- Scars have a deeper pink to red color early on before becoming hypo or hyper-pigmented

- Keloids: Web-like extensions over areas of initial wounding

- Atrophic scars: Depressed plaques

- Circumscribed or diffuse hardening of the skin

- Results from dermal fibrosis

- Detected more easily by palpation --> Feels board-like, immobile, and difficult to pick up

- Overlying epidermis may be atrophic

- Sclerosis may extend deep into the pannus, fascia, muscle, or bone

- Erythematous: Bright red, dusky, and pink

- Violaceous: Hemorrhage, deep hemosiderin, and lichenoid inflammation

- Purpuric

- Black: Melanin or necrosis

- Brown/tan: Melanin, hemosiderin, chronic inflammation, and dried serum

- Apple jelly: Granulomatous inflammation

- Blue: Deep dermal pigment, reduced hemoglobin, tattoo, and medications

- Green: Deep hemosiderin and pyocyanin pigment

- Lilac: Acute inflammation and dilation of dermal blood vessels

- Pearly: Basal cell carcinoma

- Non-blanching reddish-purple macules

- Due to extravasation of RBCs from vessels

- Color changes from bluish-red to yellowish-brown or green

- Purpuric and palpable: Inflammatory insult to vessel wall

- Small and pinpoint purpuric macules

- Large and bruise-like purpuric patches

- Persistent dilatations of small capillaries in the superficial dermis

- Visible as fine, brigh, non-pulsatile red lines

- Partially or fully disappear with diascopy

- Area of cutaneous necrosis resulting from a bland or inflammatory occlusion of blood vessels

- Tender irregularly shaped dusky reddish-gray macule or firm plaque

- Annular: Ring-shaped --> Tinea and granuloma annular

- Arcuate: Arc-shaped --> Incomplete formation of annular lesion --> Sarcoidosis and Tumid lupus

- Polycyclic: Coalescing circles, rings or incomplete rings --> Subacute cutaneous lupus erythematosus

- Serpiginous: Snake-like --> Cutaneous larva migrans

- Reticular: Net like or lacy purplish patches --> Livedo reticularis and medium vessel vasculitis

- Nummular: Coin-shaped --> Nummular eczema

- Solitary or multiple

- Grouped or scattered

- Regional or diffuse

- Dermatomal

- Blaschkoid --> Embryonic developmental lines

- Photodistributed or sun-protected

- Linear

- Koebner Phenomenon: Appearance of lesions over skin that have experienced trauma

- Acral: Palms and soles

- Truncal

- Extensor/flexor

- Intertriginous: In skin folds

- Stratum basalis: Contains germinal keratinocytes and melanocytes

- Stratum spinosum: Star shaped due to desmosomes

- Stratum granulosum: Dense basophilic granules in cells

- Stratum lucidum: Thin lucid layer just below corneum

- Stratum corneum: Basket-weave configuration

- Spinous keratinocytes: Produce keratins 1 and 10

- Basal keratinocytes: Produce keratins 5 and 14

- Thinnest on the face and eyelids

- Thickest on glabrous skin --> Palms and soles of the feet --> No hair follicles

- Basal layer cells with lucid cytoplasm surrouding nucleus

- Derived from neural crest cells

- Nucleus is round and dense

- Immunoflourescence: Mel-5

- Apocopation: Process where melanin is transferred from melanocytes to surrounding keratinocytes

- Antigen presenting cells in the skin

- Present Ag to T-cells in regional lymph nodes

- Initiate type IV HSN response

- Immunoflourescence: S100 and CD1a

- Tennis racket shaped inclusions within cells on EM

- Receptors in contact with somatosensory afferent neurons

- Associated with light touch

- Immunoflourescence: Cytokeratin (CK) 20

- Complete absence of melanocytes in lesional skin

- Proposed T-cell autoimmune attack

- Targets melanocyte antigens

- Papillary dermis: Loose CT with lots of ground substance --> Have papillary pegs that help connect and stabilize dermis to epidermis

- Reticular dermis: Dense CT with less ground substance

- Elastic fibers are higher density in reticular dermis

- Glomus cells: Thermoregulatory perivascular cells --> Involved in shunting blood in dermal blood vessels

- Meissner Corpuscles: Located in dermal papillae, light touch

- Pacinian corpuscles: Located in the reticular dermis --> Deep pressure

- Thickest on the back

- Appendages within the epidermis/dermis

- Hair follicles

- Sebaceous glands: Secrete sebum into hair follicle to lubricate hair

- Eccrine glands: Located throughout the body, produce watery sweat

- Apocrine glands: Milky fluid located in the axilla and groin --> Decapitation/snouting secretion --> Odorous sweat

- Arrector pili muscle: Smooth muscle that helps stand hair up on the skin --> Goosebumps

- Epidermal thickening

- Usually paler than normal

- Break within the epidermal layers

- Usually due to some infiltrative process such as a blister

- Keratinocytes looks round and like they are floating instead of star shaped

- Lipid infiltration between keratinocytes

- Results in vacuoles of lipid forming within the epidermis

- Acute Spongiotic Dermatitis: Minimal epidermal hyperplasia with large spongiotic vesicles

- Subacute Spongiotic Dermatitis: Moderate epidermal hyperplasia with mild spongiosis

- Chronic Spongiotic Dermatitis: Marked epidermal hyperplasia with minimal or no spongiosis

- Prototype: Seborrheic Dermatitis --> Yellowish greasy scales, dandruff, and exacerbated types in Parkinson's and HIV patients

- Parakaratosis (nuclei in top layers) is also common

- Subtype of epidermal hyperplasia --> Regular/linear

- Dermal papillae become elongated

- Prototype: Psoriasis --> Common

- Can present as plaques, guttae, inverse, or pustular

- Generally follows along with Koebner phenomenon --> Lesions appear in previous sites of skin trauma

- Auspitz sign: Pin point bleeding within lesion --> Sign of vascular involvement

- Also can occur on the nails

- Histopathology: Munro microabcess within the corneum and a spongioform pustule within the spinosum/granulosum layer

1. Vacuolar: Vacuoles form along the dermal/epidermal junction (DEJ) --> No clear delineation anymore

- Prototype: Lupus erythematosus --> Most common CT disease --> Systemic and 75-80% with skin involvement

- "Butterfly"/Malar rash on the face

- Histopathology: Vacuolated interface change, thickened BM and increased dermal mucin

- Lupus band test on IF staining for IgG and C3

2. Lichenoid: Inflammatory infiltration at DEJ --> No clear delineation either

- Prototype: Lichen planus --> Purple, pruritic, polygonal, plateaued, and papules (5 P's) --> Often associated with HCV --> Follows Koebner phenomenon

- Can involve the mucosa

- Histopathology: Hyperkeratosis, hypergranulosis, and irregular epidermal hyperplasia

- Inflammatory Infiltrate: Eosinophil, neutrophil, lymphocyte, and pauci-inflammatory

1. Intraepidermal

- Pemphigus vulgaris: Eosinophilic infiltrate --> Flaccid bullae

2. Subepidermal

- Bullous pemphigoid: Eosinophilic infiltrate --> Tense bullae

1. Sarcoidal granulomas: Non-necrotizing granulomas that lack prominent surrounding inflammation and discrete clusters of epithelioid macrophages

2. Necrobiotic granulomas: Degenerative process in CT with interspersed macrophages

- Granuloma annulare: Papular eruption which coalesce to form annular plaques --> Lateral/dorsal fingers, hands, elbows, dorsal feet, and ankles --> Increased dermal mucin

3. Necrotizing granulomas: Large central areas of necrosis

- Surrounded by dense lymphoplasmacellular inflammation

- Usually infectious --> M. leprae surrounds nerves

4. Foreign body granulomas: Contains foreign body material

- Leukocytoclastic vasculitis

- Fibrinoid necrosis of vessel walls and leukocytoclasia

- Inflammation of the vessel wall causing skin rashes

- Benign pigmented lesion

- Common in childhood

- Directly related to sun exposure --> Sun exposed skin sites

- Fade in the winter and recur in the summer months

- Overproduction of melanin within melanocytes

- Benign pigmented lesion

- Common, irregular, and pigmented macules

- Found in middle-age to elderly patients --> Increases with age

- Indication of chronic UV exposure --> Sun-exposed sites like the dorsal hands and face

- Overproduction of melanin in the stratum basale

- Nevocellular nevus --> Benign melanocytic neoplasm

1. Acquired --> Junctional, compound, or intradermal

- Junctional: Melanocytic proliferation at the DEJ

- Compound: Melanocytic proliferation in both the dermis and epidermis

- Intradermal: Proliferation only in dermis --> Most "mature" form of mole

2. Congenital --> Due to incomplete neural crest cell migration --> Get stuck in dermis

- Congenital melanocytic nevi: Can be very large

- Mongolian spot: Most common in Asian infants, less so in black infants, present at birth --> Blue/black color

- Tyndall effect: Blue/black appearance of melanin deposited in the dermis instead of epidermis

- Must think about the Mongolian spot because otherwise these can be confused for bruises and domestic abuse!!

- Melanocytic nevus that is either congenital or acquired

- Blue/gray due to Tyndall effect

- Frequently on the dorsal hands, feet, and face

- May be present at birth or can arise at any age

- Histopathology: Melanocyte proliferation in the dermis

- Atypical nevi --> "Fried Egg" appearance 

- Meet some but all of the ABCDE criteria

- Large size and pigment variations 

- Patients are at increased risk for melanoma

- 1/3 of melanoma come from dysplastic nevi

1. Melanocytes proliferate along DEJ

2. Melanocytes migrate out of stratum basale to upper layers

3. Melanocytes migrate out of epidermis into dermis

1. Melanoma in one or more 1st or 2nd degree relatives

2. Large numbers of moles (>50) --> Some atypical

3. Dysplastic nevi that demonstrate histological features

- Autosomal dominant mutation in CDKN2A gene (9q21) in 20-40% of patients with FAMMS --> Mutation does not perfectly correlate

- Lifetime risk of melanoma --> Approaches 100%

- Malignant growth of melanocytes

- Vast majority appear in sun-exposed areas

- May also occur on mucosal surfaces, iris or choroid of the eye, and leptomeninges

- 67% occur de novo and 33% from pre-existing nevi

- Least common skin cancer --> High mortality though

- Incidence is increasing

- Risk factors: Fair skin exposure to sun, childhood sunburns, episodic UV exposure, Hx and FHx of melanoma, lots of nevi (>50), irregular nevi, and immunosuppression

- 30 million people use tanning beds in the US

- 74% more likely to develop melanoma than people who have never tanned indoors

- Asymmetry

- Border irregularity

- Color variation

- Diameter greater than 5 mm

- Evolution --> nevus that has changed shape or gotten larger

- Look for the "ugly duckling" 

1. In situ --> Confined to epidermis, very low metatastatic potential

2. Superficial spreading melanoma (70%): Variable radial growth prior to vertical/invasive growth

3. Lentigo maligna melanoma (5%): Head and neck, long radial growth phase (lentigo maligna) before vertical phase (lentigo maligna melanoma)

4. Acral lentiginous melanoma (5%): Only melanoma present in dark skinned individuals (blacks, Asians) --> Occurs on the palms, soles, and nail beds --> Kit mutation and unrelated to UV exposure

5. Nodular melanoma (20%): Very hard to diagnose, almost no radial growth --> Large vertical growth phase and high metastatic potential

- Initial radial growth phase that is usually entirely confined to the epidermis

- Vertical growth phase where the tumor grows down into the dermis, adjacent tissues and possibly lymphatics

- Histopathology: Nests of melanocyte proliferation along stratum basale but also throughout the entire epidermis and possibly down into the dermis depending on phase

1. Breslow depth: Depth and extent of involvement throughout the epidermis, dermis and subcutis

- Tis: in situ, T1 (<1.0 mm), T2 (1.01-2.0mm), T3 (2.01-4.00 mm), and T4 (>4 mm)

2. Ulceration: Ulceration means more severe disease

3. Mitotic rate: Higher rate means higher metastatic potential of the tumor

1. Wide local excision: 0.5 mm to 2 cm margins depending on the tumor --> 2 cm margins for tumor >1 mm depth

2. Sentinel Lymph Node Biopsy: Considered for lesions >1 mm deep, ulcerated, or mitotically active

- Follow lymphatic drainage, remove and section nodes --> Determine if node is affected, if not then stage from there, if it is then continue to further nodes to determine extent

- Before 2011: High-dose IL-2 and dacarbazine --> 10% reponse rates and no real benefit in survival

1. Ipilimumab: Promotes immune response against tumor by blocking the CTLA4 pathway

- CTLA4 normally functions to stop an immune response, blocking this pathway would perpetuate immune response against tumor

- Extended lifespan in patients with stage IV melanoma

2. Vemurafenib: BRAF inhibitor

- BRAF mutation in 40-60% of melanoma --> Mutation exists in 80% of benign nevi to though!!

- BRAF pathway is crucial for cell survival and proliferation

- Blocking BRAF --> Blocks cell survival and proliferation

- Most common type of cancer in the US

- 40-50% of people who live to age 65 will have skin cancer at least once

- About 90% of non-melanoma skin cancers are associated with UV exposure --> Sun exposed areas

- Fair skinned individuals --> Blue eyes with blonde/red hair

- Unprotected sun exposure --> Blistering sunburns (BCC/melanoma) or chronic sun exposure (Actininc keratoses/SCC)

- Personal history --> 50% recurrence

- Family history

- Age

- Basal cell nevus syndrome

- Mutation of PTCH tumor suppressor gene

- Autosomal dominant but may be sporadic too

- Presentation: Widespread distribution of BCCs --> 100-1,000

- Other features: Palmar and plantar pits, odontogenic cysts of jaw, skeletal abnormalities, mental retardation, meningioma, and ovarian tumors

- Autosomal recessive --> Rare

- Mutation in DNA excision repair mechanisms

- Presentation: Numerous BCC and SCCs with a higher risk of melanoma --> >1,000 times more likley

- May be associated with progressive neurologic degeneration and increased risk of internal malignancies

- Lack of normal protective pigmentation --> Lack of melanin and melanocytes

- Red eyes, very fair skinned, blonde/white hair

- Sun protective clothing

- Avoid sun during the hours of 10am-3pm --> Most UVB rays --> Seak out shade

- Sunscreen: Broad spectrum that covers UVA as well --> 15-30 SPF

- SPF: Time with product to burn/Time without product to burn

- SPF=1/UVB transmission --> SPF 10 --> 1 in 10 UVB rays gets through

- UVA protection: Broad spectrum or opaque sunscreens

- Most common of ALL cancers

- Proliferation of basal keratinocytes

- Low metastatic potential generally --> 1 in 100,000

- May become disfiguring if left untreated for long periods of time

1. Nodular: Appears as elevated papule on skin --> Dark purple, peripheral palisading, and retraction of surrounding epidermis

2. Superficial: Very superficial, just looks red on the skin

3. Infiltrative: Red almost ulcerated lesion --> Scattered and infiltrating clusters of basal keratinocytes --> Can appear very small on the surface while actually being very large 

1. Surgical Excision/Mohs Technique: 95-99% cure rate

- Normally 4 mm margins necessary

- Much more tissue sparing and smaller margins necessary with Mohs Technique --> Frozen sections examined in office, more precise but takes a LONG time for patient

2. Electrodessication and curettage: 90% cure rate

- Repeated scarping with curettage and electrodessication process to completely remove lesion

3. Cryotherapy: 80-95% cure rate

4. Photodynamic therapy: 80% cure rate, only for sBCC

5. Topical chemotherapy: 80% cure rate, only for sBCC

6. Topical immunotherapy: 80% cure rate, only for sBCC

7. Radiation therapy: Variable success

8. Oral treatment: Vismodegib --> VERY expensive and only for very advanced disease

- Blocks to SMO pathway which is crucial for cell survival and proliferation

- 30-45% of patients have at least partial response

- Side effects: Teratogen, constitutional, altered taste, muscle spasms, and hair loss

- Location: Face, neck, hand, foot --> Tissue sparing is important in these areas

- Aggressive histology: Poorly to moderately differentiated, infiltrative BCC, and other rare invasive tumors (Merkel cell)

- Larger size (>2cm)

- Recurrent tumors

- Tumors previous excised with positive margins

- Tumors on previously irradiated skin

- Ill-defined borders of tumor

- Ill-defined pink scaly patch --> Sandpaper texture

- Sun-exposed skin

- p53 mutation --> Abnormal cell growth and dysfunctional apoptosis

- Actinic cheilitis also common

- Histology: Abnormal squamous cells involing part but NOT all of the epidermis

- Treatment: Cryotherapy, topical 5-FU, photodynamic therapy, imiquimod (immunotherapy), and ingenol mebutate

- If untreated --> Very few will become SCC

- Topical immunotherapy

- Uses: Condyloma, actinic keratoses, and superficial BCCs

- Applied twice weekly for 16 weeks

- Advantages: Field therapy

- Disadvantages: Dramatic inflammatory response and long-term therapy may be necessary

- Aminolevulanic acid is applied an hour before therapy

- Utilizes the porphyrin pathway

- Pre-treated skin is exposed to blue light

- ALA --> protoporphyrin IX --> Photosensitization

- Free radicals are formed that will attack the tumor cells 

- Persistent thick, warty, rough, scaly bumpy plaques that can bleed with minor trauma

- Risk factors: Sun exposure, immunocompromised patients, etc --> Same as AK

- Usually doesn't metastasize as long as it is treated in a timely manner --> May be disfiguring though

- Prevalence: 700,000 cases per year --> 2,500 deaths

- Often preceeded by pre-existing lesions --> Actinic keratoses (>60%), condyloma acuminata (HPV-16+18), and burns

- Can also affect the mouth or other mucosal surfaces

- Mutations: p53 (47%) and NOTCH1 (15%)

- NOTCH1 or NOTCH2 mutations in ~75% of cutaneous lesions --> Loss-of-function mutation

- Not associated with HPV or other viral infections

- Histopathology: Invasive carcinoma of the supra-basal keratinocytes --> Normal or atypically appearing cells --> Keratinization generally occurs

- Bowen's Disease

- Well demarcated thin erythematous scaling plaques

- Similar to plaques of psoriasis and eczema

- Non-inflammatory and often solitary

- Malignancy is confined to the epidermis --> Do not metastasize

- There is a risk of progression to true SCC --> Dermal invasion

- Surgery/Mohs Technique

- Electrodessication and curettage

- Cryotherapy

- Photodynamic therapy

- Topical chemotherapy

- Topical immunotherapy

- Radiation therapy

- Recurrent tumors

- Large tumors --> Greater than 2 cm wide and/or 4 mm thick

- Location: Lip, ear, and scalp

- Immunosuppressed patients --> Transplants patients --> 95% of cancers in these patient are BCC or SCC

- Histology: Poorly differentiated and perineural invasion

- Hx of radiation at site

- Usually travel first to nodes before distant spread

- Shorter wavelength --> Shallower penetration

- Longer wavelength --> Deeper penetration --> Only red will go through the entire arm

- Molecules that absorb photons of light

- May undergo photochemical reactions after absorbing light

- No absorption --> No reaction

- Major chromophores: DNA, melanin, porphyrins, and hemoglobin

1. Acute: Tanning, sunburn, and vitamin D production

- Tanning: Increased melanin pigmentation due to acute or chronic sun exposure --> Protective mechanism

- Sunburn: Inflammatory response to acute UV injury --> Erythema due to dilation of blood vessels --> Begins within 2-4 hours, peaks 12-24 hours after and resolves within a few days

- Vitamin D Production: UVB produces pre-vitamin D3 --> Liver and kidney for full activation

2. Chronic: Photoaging and photocarcinogenesis

- Photoaging: Coarse, rough, wrinkled, sallow, and irregularly pigmented skin caused by chronic sun exposure

- Photocarcinogenesis: Continuous DNA and cell damage due to UV exposure --> Neoplasms

- Most common photodermatitis --> 2-5% of population

- Sun allergy or sun poisoning

- Caused by broad UV spectrum

- Presentation: Pruritic papules and plaques on sun-exposed areas

- Lesions will resolve within 2 weeks if not exposed to UV light again --> No scarring

- Patient will harden with repeated sun exposure --> Worst in early spring and best in mid to late summer

- Localized to skin or systemic disease

- Many different characteristic lesions --> Butterfly rash across the cheeks, above the eyebrows, bridge of the nose, etc

- Photodistributed across sun-exposed skin

- Photosensitivity may be a sign of worsening systemic disease

- Immune target: UVA-modified DNA --> Anti-dsDNA

- Inherited or acquired enzyme defects

- Enzyme defect --> Build up of heme biosynthesis pathway intermediates (porphyrins)

- Sorbet band light (400-410 nm) --> Responsible for damage --> Light absorbed by unsaturated double bonds on the rings of intermediates

- Produces free radicals --> Epidermal damage

1. Congential/Erythropoietic/Gunther's (EP): Very rare, most severe --> AR transmission --> Red teeth and bones, bullae, vesicles and erosions form due to sun exposure, scarring alopecia, and scleroderma-like changes

2. Porphyria Cutanea Tarda (PCT): Acquired but AD if congenital --> Middle aged alcoholic and women or men on oral contraceptives --> Bullae and crusted erosions form after sun exposure

3. Erythropoietic Protoporphyria (EPP): AD disorder --> Early childhood photosensitivity --> Exaggerated sunburn, swelling/urticaria, purpura, and occasional bullae --> Gallstones also develop in these patients due to improper heme breakdown

- Abnormal reaction to light mediated by a drug or endogenous substance

- Drug-Induced: Ring-structured compounds with unsaturated double bonds --> UVA induced

- Typical photosensitizers: Sulfa drugs, doxycycline, nalidixic acid, phenothiazine, amiodarone, coal tar, NSAIDs, and thiazide diuretics

- Can also affect the nails

- Psoralens --> From apricots, figs, limes, celery, and figs --> Can cause photosensitivity if on skin

- Photosensitivity reactions can be used for treatments!! --> PUVA for psoriasis

- Exaggerated sunburn or suntan

- Normal and intact epidermis --> Just red

- Sun-exposed skin sites

- Not immunologically mediated

- Should occur in all people exposed to sufficient amounts of drug and light

- Photo-distributed rash

- UV associated hypersensitivity reaction

- Drug molecules are altered when they come in contact with light --> Hypersensitivity

- PMLE: UVB and UVA

- LUPUS: UVB, UVA, and some visible --> Largest spectrum

- Porphyrias: Sorbet band --> UVA and visible

- XP: UVB

- Drug photosensitivity: UVA with a little UVB

- All these conditions, except XP, will need special broad spectrum sunscreens!!!

- 80-90% of American teenagers are affected

- 3-6% of adult men and 5-12% of adult women are affected

- Causes similar levels of emotional impairment as epilepsy and asthma

- Unemployment is higher in adults with acne as well

- Pathogenesis: Follicular hyperkeratinization, P. acnes infection, inflammation and increased sebum production

- Early comedone --> later comedone --> inflammatory papule/pustule --> nodule/cyst

- Hyperpigmentation often results after healing of acne lesions --> Not truly an acne lesion though

- Open comedone: Black head --> Keratin plug visible

- Closed comedone: White head --> Follicle is closed so keratin plug is not visible

- Higher levels in adolescents with acne

- No correlation between P. acnes number and the severity of disease

- P. acnes --> Increased sebum production

- Antibiotic therapy targets reduction in P. acnes counts

- Topical retinoids

- Topical dapsone

- Benzoyl peroxide

- Salicylic Acid

- Topical or oral antibiotics

- Oral contraceptives

- Spironolactone

- Isotretinoin

- Different prescription versions and formulations (creams, lotions, gels)

- Tretinoin (all-trans-retinoic acid), adapalene, and tazarotene

- Mechanism of Action: Normalize follicular keratinization and decrease keratinocyte adhesiveness --> Anti-inflammatory

- Work along the vitamin A pathway --> Binds specific receptors, exert their effects and then metabolize to inactive forms

- Two distinct types: Retinoic acid receptors (RAR) and retinoid X receptors (RXR) --> RAR and RXR form heterodimer --> DNA regulation/transcription factors

- Tretinoin --> Binds only to RAR

- Application: Apply pea sized amount to dry face and no spot treatment

- May worsen acne initially and takes 6-8 weeks to work

- Contraindications: Pregnancy (category X for tretinoin and category C for trazarotene)

- Anti-inflammatory effects --> Neutrophil suppression, scavenging of reactive oxygen species and antimicrobial activity by inhibiting bacterial dihydropterase synthase

- Safe for patients with G6PD deficiency and sulfonamide allergy

- Can turn skin a tan/orange hue if used in combination with benzoyl peroxide products

- Common in OTC treatments

- Reduces P. acnes --> Generates reactive oxygen species within sebaceous follicle

- Improvements as early as five days after initiation

- Reduction better with leave on products rather than washes

- Can be used to help prevent P. acnes resistance

- Can be drying to the skin

- Common in OTC treatments

- AKA beta-hydroxy acid

- Mechanism: Dissolves intracellular cement holding the cells of stratum corneum

- Comedolytic and anti-inflammatory effect

- Lipid soluble --> Penetrates pilosebaceous unit

- Very drying to skin

- Clindamycin: Most commonly used

- Erythromycin: Lots of resistance

- Available in gels, creams, lotions, solutions, pledgets, and foams --> Twice daily

- Mechanisms: Decreases P. acnes and inflammation

- Disadvantages: Resistance

- Advantages: Less skin irritaiton than topical retinoids

- Used in combination with benzoyl peroxide for the best results

1. Tetracyclines (Tetracycline, minocycline, doxycycline): Inhibits 30S ribosomal subunit

- Indications: Moderate to severe acne, failed topical treatment, moderate acne scarring, and involvement of shoulders, back or chest

- Side effects: GI upset (tetra), photosensivity (doxy), pseudotumor cerebri, and vestibular disturbances (mino)

- Minocycline crosses BBB and has other specific side effects --> Hypersensitivity, drug-induced lupus, and blue-grey hyperpigmentation

2. Macrolides (Erythromycin, clindamycin, and azithromycin) --> Irreversibly inhibits 50S subunit

- High resistance to erythromycin

- GI upset

- Sub-antimicrobial doxycycline: Low dose (20 mg) --> Only anti-inflammatory effect but not anti-microbial

3. Trimethoprim-Sulfamethoxazole (Bactrim)

- Anemia, thrombocytopenia, and agranulocytosis

4. Cephalexin --> Possible MRSA development

- Duration of therapy: Debated but usually 3-4 months and low doses (sub-antimicrobial dosing)

- 13-cis-retinoic acid --> Effects all four pathogenic mechanisms of acne

- Duration of treatment: 5-6 months (20 weeks)

- 80% of patients are CURED of their acne

- Mechanism: Unknown --> Does not bind retinoid receptors directly --> Isomerization to all-trans-retinoic acid --> Interacts with receptors

- Effects: Comedolytic, reduces sebaceous gland size, decreases sebum production, and inhibits P. acnes

- Therapeutic effects: Reverses comedone formation, reduces sebum levels, reduces P. acnes, reduces inflammation, and possible acne cure

- Side effects: Teratogenicity (category X), psychiatric (depression), IBD (possible), lipid disorders, xerosis/cheilitis, arthralgias, and pseudotumor cerebri

- Teratogenicity: Difficult to assess risk of teratogenicity, increased risk of spontaneous abortions, and 1/4 of fetuses brought to term have birth defects

- Most common in female patients --> Before menses

- May or may not actually have endocrine disorder

- Enhanced hormonal activation of sebaceous glands

- Presentation: Sudden onset, adult onset, irregular menses, hirsuitism, and cyclical acne flares

- Distribution: Lower face, jawline, neck, or chin

- Treatments: Topical  treatments, oral antibiotics, oral contraceptives, and sprionalactone

- Suppresses andorgen production --> Suppresses LH production and decreases adrenal androgens

- Increases SHBG which binds testosterone

- Inhibits 5-alpha reductase

- Approved OCPs: Estrostep, Ortho Tri-Cyclen, and Yaz --> Low concentrations of estrogen and progestin

- Androgen receptor blocker

- Diuretic and antihypertensive

- Not FDA approved for acne

- Decreases the effect that androgens have on the sebaceous gland

- Decreases sebum production by 35-50%

- Mechanism: Androgen receptor blocker, inhibits 5-alpha reductase, decreases type II 17 B-hydroxysteroid dehydrogenase, increased levels of SHBG, and decreased sebocyte proliferation/sebum secretion

- Side effects: Breast tenderness/enlargement, orthostasis, polyuria, menstrual irregularity, increased potassium, and avoid pregnancy

- Common condition --> More common in fair-skinned patients

- Higher incidence in women

- Usually diagnosed after 30 years old

- Pathogenesis: Unknown but vascular hyper-reactivity, neurally mediated, thermal stimuli, inflammatory response to leaky vessels, defective skin barrier, and demodex mites in hair follicle

- Triggers: Exercise, alcohol, coffee, and spicy foods

1. Erythematotelangiectatic/Vascular

- Erythema and telangiectasias are characteristic --> Generalized over the face

2. Papulopustular

- Presents as papulopustular lesions on the face

3. Ocular

- 50% of rosacea patients --> Dry eye, pruritis, and photosensitivity

- Eye disease doesn't correlate with severity of skin disease

4. Phymatous/Rhinophyma

- Generalized erythema, edema, and follicle dilation of the nose

- Sun protection

- Avoidance of triggers

- Oral vs. topical therapy

- Laser therapy

1. Vascular --> Laser therapy

2. Phymatous --> Surgical and laser therapy

3. Ocular rosacea --> Oral antibiotics

4. Papulopustular --> Oral antibiotics, topical metronidazole, topical azeleic acid, etc

1. Inflammatory lesions and ocular rosacea

- Oral: Tetracylcine, minocycline, doxycycline, and sub-antimicrobial doxycycline

- Topical: Metronidazole --> Effective in maintaining remission, no effect on telangiectasias

- Doxycycline: Inhibits gelatinases and downregulates cytokines

2. Flusing treatment

- Beta blockers

- Clonidine

- Brimonidine (topical)

3. Extreme or recalcitrant cases

- Isotretinoin

- Clindamycin

- Erythromycin

- Metronidazole

- Azelaic acid

- Brimonidine

- Sodium sulfacetamide/sulphur

- Formations: Cleansers, lotions, creams, and gels

- Best for the papulopustular form

- Oral and topical meds are ineffective

- Pulsed dye laser (595 nm)

- Intense pulsed light device

- Usually in men

- Lower half of the nose

- Soft tissue hypertrophy with overgrowth of sebaceous glands and connective tissue

- Treatment: Surgical sculpting via CO2 laser, dermabrasion, and surgical revision

- Types of edema: Transient, post-flushing soft edema and long-lasting, hard, non-pitting

- Sudden severe eruption of rosacea

- Affects the face

- Usually on women

- Can affect large portions of the skin of the face

- Common, acute, self-limited papulosquamous eruption

- Presents in health adolescents and young adults (10-35 years) --> Peaks during adolescence

- Absence of systemic manifestations

- Spontaneous resolution

- Etiology: HHV-7 > HHV-6

- Prodrome in 5%

- Herald patch in >50%

- Trunk and proximal extremities

- Christmas tree pattern on back

- Face, palms, and soles usually spared

- 6-8 week duration

- Spontaneously resolves

- 25% associated pruritis

- Atypical: Body folds (groin, axilla, neck, etc)

- Patient education and reassurance

- Treat pruritis with antipruritic lotions, low-medium strength topical corticosteroids, UVB phototherapy, and oral antihistamines

- Recurrence is unlikely

- Chronic, immune-mediated disorder

- Results from a polygenic predisposition combined with environmental triggers

- Presents at any age --> Peaks 20-30 years and 50-60 years

- Systemic manifestations: Psoriatic arthritis (20-30%), cardiovascular disease, and metabolic syndrome

- Rash: Bilaterally symmetric white scaly plaques

1. Chronic plaque --> Chronic presentation over the entire body with white ring around papule/plaque (Woronoff's ring)

2. Erythrodermic --> Poorer prognosis

3. Guttate --> Small scaly papules often following streptococcal throat infection

4. Pustular

5. Palmoplantar --> Present on palms and soles of feet

6. Inverse --> Within body folds

- Severe exacerbation can be a sign of HIV infection

- Follows along with the Koebner phenomenon

- Histopathology: Acanthosis with dermal papillae and rete ridge lengthening

- Drug-induced: Beta-blockers, lithium, anti-TNF agents, ACEIs, and femfibrozil

- Exclude triggers and minimize trauma (Koebner phenomenon)

- Reconcile the extent and severity of disease with the patient's own perception of their disease

- Mild to moderate involvement --> Topical corticosteroids and vitamin D3 analogue to inhibit plaque formation

- Vitamin D3 analogue: Activates transcription factors that inhibit keratinocyte proliferation and activate keratinocyte differentiation

- Second line agents: Phototherapy or systemic agents (methotrexate, prednisone, etc)

- Idiopathic inflammatory disease of the skin, hair, nails, and mucous membranes

- Most common in 50-60 years old

- Associated with HCV infection --> Particularly with oral involvement

- Drug-induced: Antihypertensives (ACEIs, B-blockers, and diuretics), antimalarials, and anti-TNF agents

- Lesions develop over several weeks

- Symmetrical and bilateral over distal lower extremities

- Flexural areas of the wrists and arms

- No face or palmoplantar involvement

- Can have mucosal (groin, vagina, mouth), nail, or scalp involvement

- Koebner phenomenon --> Appear after trauma

- Clinical features: Pruritic, polygonal, planar, purple, papules (5 P's), and Wickham's Striae

- Striae can be present on skin and in the mouth

- Scalp involvement can result in balding with destruction of hair follicles

- Superficial dermal inflammatory infiltration

- Acanthosis

- Consider drug-induced --> Withdrawal causative agent

- Mild disease --> Topical or intralesional corticosteroids, and topical calcineurin inhibitors

- Severe disease --> Systemic corticosteroids, acitretin, photochemotherapy, hydroxychloroquine (antimalarial), and systemic immunosuppressive agents (methotrexate, etc)

- Common, mild chronic eczema

- Typically confined to skin with high sebum production (face) and large body folds

- Etiology: Active sebaceous glands, abnormal sebum composition, and Malassezia furfur infection

- Infantile form: <3 months old

- Adult form: Chronic, peaks between 40-60 years old

- Extensive and therapy-resistant disease may be a marker for HIV infection, Parkinson's disease, and mood disorders

- Ill-defined patches or thin plaques

- Pink-yellow to dull red to red-brown

- Bran-like to flaky "greasy" scales

- Areas rich in sebaceous glands --> Scalp, face, ears, and presternal region

- Mild disease course with chronic relapsing pattern

- Infants: <3 months --> Scalp involvement

- Topical antifungals --> Shampoos and creams

- Low-potency topical corticosteroids and emollients

- Zinc pyrithione and tar shampoos (Selsun blue)

- Tends to relapse if treatments aren't continued

- Inflammatory skin condition

- Due to dysfunctional epidermal barrier --> Falagrin mutation

- Associated with other atopic conditions (ashtma, dermatitis, and rhinoconjunctivitis)

- Intense pruritis and chronic/chronically relapsing course

- Multiple subtypes: Infantile, childhood, adlescent, and senile-onset

- Can greatly effect the quality of life of patients

- Sleep disturbances, psychological distress, social isolation, disrupted family dynamics, and impaired functionality

1. Infantile (<2 years): Seborrheic dermatitis of scalp at 1-2 months old

- Edematous, erythematous pauples and plaques --> Vesicuation, oozing, and serous crusting

- Involved areas --> Cheeks, scalp, neck, extensor aspects of extremitis, and trunk --> Sparing of the central face and diaper area

2. Childhood (2-12 years): Subacute lesions most common

- More dry and papular lesions in well circumscribed scaly patches

- Less exudative lesions --> Become lichenified

- Inolved areas --> Periorificial, wrists, ankles, hands, feet, and antecubital and popliteal regions

- Xerosis typically becomes pronounced and widespread

3. Adolescent/Adult (>12 years): Subacute to chronic lesions

- Dry, scaling erythematous papules/plaques

- Lichenified plaques

- Involved areas --> Flexural folds, chronic hand dermatitis, facial dermatitis (severe on eyelids), and prurigo nodularis

- Atopic Stigmata: Papules around the eyes, numerous pinpoint papules, hyperlinear palms, or

hypopigmented lesions on the face

4. Senile-onset: >60 years old

- Education about disease

- Skin care aiming to keep skin moisturized and help maintain skin barrier --> Immediate application of oily moisturizer after showering

- Anti-inflammatory therapy to control subclinical inflammation

- Identification and elimination of triggers

- Adverse inflammatory reactions --> 80% irritant and 20% allergic

- Reaction is dependent on the specific chemical, duration of exposure, and individual host response

- Presentation: Well-demarcated, very itchy, erythematous vesicular/scaly patch or plaque

- Patches and plaques will lichenify when chronic

- Distribution: Linear or localized --> Object rubbing against skin and hand/foot dermatitis

- Type IV hypersensitivity: cell-mediated, delayed-type

- Requires prior sensitization

- Spongiotic epidermal changes

- Initial sensitization: Langerhans cellstrap the antigen --> Travel to lymph node, present to T-cells --> Specific T-cells multiply and circulate

- Re-exposure: Sensitized T-cells bind allergen-activated Langerhans cells --> Local immune response --> Epidermal changes/blistering

- Common allergens: Urushiols (poison ivy/oak), nickel, fragrances, neomycin, thiuram mix (rubber), preservatives, and paraphenylenediamine

- Occupational dermatitis --> Cleaning supplies, etc

- Acute insult to the skin or cumulative damage over time

- Common irritants: Soaps, detergents, cleaners, friction, etc. 

- Not immune-mediated

- Spongiotic epidermal changes

- Withdrawal allergen/irritant

- Protection of exposed areas

- Topical corticosteroids

- 2-3 weeks of systemic steroids if severe

- Recurrent whealing of the skin

- Acute vs. chronic --> More or less than 6 months

- Common causes: Medication, infection or food

- Pathogenesis: Type I hypersensitivity --> IgE and mast cell mediated --> Cytokine release

- Small or large pink erythematous and edematous wheals --> Peripheral rim of pallor

- Single or multiple --> Diffusely distributed

- Wheals last <24 hours and fade without bruising or hyperpigmentation

- Typically intensely pruritic

- Cooling lotions

- Avoid triggers

- Dietary changes to exclude food triggers

- Antihistamines

- Topical or systemic corticosteroids

- Immunotherapy

- Skin is most common target for adverse drug reactions --> 75-90% of drug reactions

- 1-5% of patients on NSAIDs, antibiotics or anticonvulsants

- Causative agents: Penicillins, sulfonamides, cephalosporins, anticonvulsants, allopurinol, and thiazides

- 2% of drug reactions are serious --> DRESS, Stevens-Johnson and Toxic Epidermal Necrolysis (TEN)

- Presentation: Erythematous macules in symmetric distribution, can become slightly palpable --> 1-7 days after initiating drug

- Begins on trunk and upper extremities

- Disappears spontaneously after 1-2 weeks without complications/sequelae

- More severe disease: Facial edema, marked peripheral blood hypereosinophilia, and mucous membrane lesions, painful, or dusky skin

- Discontinue agent

- Topical antipruritics and corticosteroids

- Systemic corticosteroids

- Benign, usually self-limited cutaneous disease

- Unkonwn etiology

- Most common in children and young adults

- One or more papules with centrifugal enlargement and central clearing

- Usually asymptomatic but mild pruritis may be present

- Prognosis: Spontaneous resolution within 2 years (50%), 40% recurrence, and duration ranges from weeks to decades

- Annular or arcuate lesion that may be skin-colored, erythematous or violaceous

- 1-5 cm in diameter

- Commonly on the dorsal hands and feet, ankles, lower limbs and wrists --> Rarely on the face

- Annular margin is firm upon palpation and may be continuous or coalesce

- Epidermis is usually normal

- Solitary umbilicated papules or nodules may also occur especially on the fingers

- Reassurance and clinical observation

- High-potency topical corticosteroids with or without occlusion

- Intralesional corticosteroid injections

- Oral niacinamide, isotretinoin, antimalarials, dapsone, and pentoxifylline

- Epidermal neoplasm

- Can present anywhere on the body

- Round or oval, well-demarcated or "stuck on"

- Color: Skin-colored to tan to brown to gray to black --> May become inflammed

- Lesions may be macular

- Etiology is unknown

- Epidermal lesion

- More commonly on darker skinned people

- Small seborrheic keratoses

- Often periocularly

- Epidermal lesion

- Benign proliferations of epidermis --> Commonly on the fingers and feet

- Caused by HPV viruses

- Verrucous papules with thrombosed capillaries (black dots)

- HPV-1 --> Plantar warts

- HPV-2,4,27,29 --> Common warts

- HPV-6,11 --> Genital warts

- HPV-16,18 --> Cervical cancer

- Epidermal lesion

- AKA Sebaceous cyst

- Derived from upper portion of hair follicle epithelium

- Firm, subcutaneous, mobile, and a black punctum

- May get inflammed

- Purulent, cheesy, and malodorous material when drained

- Treatment: Excision, hot compresses, incision and drainage, intralesional steroids, and antibiotics

- Epidermal lesion

- Tricholemmal cyst

- Generally on the scalp --> >90%

- Occurs in 5-10% of the population

- Almost always benign  but can be locally aggressive, large and ulcerated

- Treatment: Excision

- Epidermal lesion

- Small, EIC-like lesions found on the central face --> Periocularly and eyelids

- Contains keratin

- Can affect any age group

- Single to numerous present

- Small, smooth, white, firm, and spherical

- May be congential

- Treatment: None unless concerning to patient

- Epidermal/dermal lesion

- Solitary or multiple, hard, solitary, smooth, dome-shaped or depressed papules/nodules

- Slow growing

- Variety of colors --> Usually brownish to tan

- Commonly on extremities (lower)--> Sometimes on trunk

- Possibly tender

- Most commonly in females (4:1)

- Dimple/Fitzpatrick's Sign: Lateral pressure on the lesion producing dimpling/depression

- Epidermal/dermal lesion

- Benign neoplasms of skin and blood vessels

- Hyperkeratotic vascular plaques

- Commonly found grouped on the scrotum

- May bleed --> Especially if traumatized

- Possible solitary lesions

- Dermal lesion

- Skin tags

- Usually asymptomatic but occassionally tender/inflammed/irritated

- Favors axillae, groin, and inframammary area

- Neck and eyelids also common

- Soft, flesh colored pedunculated papules

- Usually not removed because they recur very frequently

- Dermal lesion

- Proliferation of sebaceous glands

- Often in older patients

- Located on coarse, oily/sebaceous skin

- Multiple yellowish and lobulated papules --> 1-3 mm in diameter

- Centrally umbilication is characteristic

- Easily confused with basal cell carcinoma

- Dermal/Subcutis lesion

- Multiple bright red to violaceous, dome-shaped papules

- Tiny macules also possible

- Caused by numerous dilated capillaries surrounded by endothelial lining

- After age 30

- Most commonly found on the trunk

- Dermal/Subcutis lesion

- Exuberant scar tissue at the site of cutaneous injury

- Rarely spontaneous

- Keloid extends outside the boundaries of original scar

- More common in darker skinned individuals

- Commonly on earlobes, chest, and upper back

- Presentation: Skin-colored to red or hyperpigmented tumors/nodules

- May be tender or pruritic

- Benign tumor of subcutaneous fat

- Skin-colored, soft, freely movable, less well-defined than cysts

- Asymptomatic --> Variants with increased vasculature can be painful

- Fever and rash

- Fever and blisters/denuding skin

- Rash in an immunocompromised host

- Palpable purpura

- "Full body redness"

- Toxin-mediated cleavage of the skin at the granular layer of the epidermis --> Flaccid bullae

- Risk factors: newborns, children, or adults with renal failure

- Causes: Staph strains producing exfoliative toxin A and B

- Derm findings: Erythema periorifically on the face, neck, axilla, and groin --> Generalized within 48 hours --> Sloughing in 1-2 days and recovery in 2 weeks

- Nikolsky sign: Lateral pressure on the lesions causes dimpling

- Presentation: Prodrome with fever, malaise and sore throat

- Mortality: 3% in kids, >50% in adults and ~100% in adults with underlying conditions

- Necrotizing infection of the subcutaneous tissue

- Type I: Mixed anaerobes, G- aerobic bacilli, and enterococci

- Type II: Group A strep

- Risk factors: Diabetes, peripheral vascular disease, anad immunosuppression --> Diseases with decreased circulation already

- Derm findings: Diffuse edema and erythema --> Bullae --> Burgundy color --> Gangrene

- Presentation: Severe pain, anesthesia, crepitation, and exudates --> Shock and organ failure are possible

- Management: Surgical debredement and IV antibiotics

- Disseminated presentation of Neisseria meningitides

- Transmission: Respiratory droplets

- Most commonly in young adults and children

- Risk factors: Asplenia and immunoglobulin or terminal complement deficiencies

- Derm findings: Abrupt onset of maculopapular or petechial eruptions on the palms, soles, trunk, or lower extremities --> Progresses to purpura with "gun metal gray" center within hours

- Can present with or without mucosal involvement

- Presentation: Fever, chills, malaise, headache, photophoia, nuchal rigidity, DIC, and shock

- Rickettsia rickettsii carried by ticks --> Possible eschar at site of bite

- Derm findings: Purpuric macules and papules --> Starts on wrists and ankles within 2 weeks --> Palms and soles --> Trunk and face

- Skin becomes hemorrhagic and petechial over 2-4 days

- Presentation: Fever, headache rash, and mutli-organ involvement

- Mortality: 30-70% mortality if untreated and 3-7% if treated

- Treatment: Doxycycline --> Even in kids!!!

- Kaposi's varicelliform eruption

- Due to HSV infection --> HSV1>HSV2

- Risk factor: Any disease with impaired skin barrier

- Derm findings: 2-3 mm umbilicated vesicles --> Coalesce to form scalloped erosions and hemorrhagic crusts

- Systemic involvement possible

- VZV/HSV3

- Primary/Chickenpox: Pruiritic erythematous macules and papules --> Vesicles with clear fluid surroudned by narrow red halos --> Lesions in all stages of development

- Primary infection begins on face and moves down

- Presentation along dermatomes

- Secondary/Zoster: Same pruiritic erythematous macules and papules

- Derm findings: Vesicles that coalesce and ulcerate like other herpes viruses

- Prodrome in 90% of patients

- V1 of trigeminal involvement needs ophthalmology consult to prevent blindness

- Disseminated: >20 vesicles across midline or outside of primary dermatome

- Diagnosis: Tzanck smear

- Treatment: Oral or IV acyclovir, etc

- HIV or immunosuppressed patients

- Elderly --> Polypharmacy

- Genetic predisposition

- Drug induced mucocutaneous reaction

- Requires the involvement of 2 or more mucosal surfaces

- Meds: Sulfonamides, anticonvulsants, allopurinol, NSAIDs

- Usually presents 1-3 weeks after drug ingestion

- SJS: BSA <10% and TEN: BSA >30%

- Presentation: Fever, chills, malaise, stinging eyes, difficulty swallowing and urinating

- Derm. findings: Skin tenderness, dusky erythema, epidermal detachment and desquamation, and mucosa involvement

- Management: Ophthalmology and urology consults, IVIG, and systemic steroids

- Anticonvulsant, drug-induced, and drug-induced multi-organ hypersensitivity syndrome

- Derm findings: Maculopapular/morbilliform and urticarial eruption --> Vesicles, bullae, pustules, purpura, targetoids lesions, and erythroderma are also possible

- Facial edema is also common

- Presentation: Fever, eosinophilia, lymphadenopathy, hepatic damage, endocrinopathy (hypothyroid), kidney, lung, and heart involvement

- Hepatic damage can lead to fulminant hepatitis in 10% of patients

- Idiosyncratic

- Problem with drug detoxification

- Common onset 2-6 weeks after exposure

- Common causes: Aromatic anticonvulsants, sulfonamides, minocycline, allopurinol, antiretroviral drugs, NSAIDs, and calcium channel blockers

- FAS-ligand circulating through the bloodstream --> Apoptosis 

- Increased intravascular permeability

- Derm findings: Well circumscribed acute cutaneous edema due to increased intravscular permeability --> Painful but NOT pruritic

- Commonly found on the face, lips, extremities, and genitalia

- Presentation: Abdominal pain and respiratory distress

- Etiology: Idiopathic, drug induced (ACEI, penicillin, and NSAIDs), allergens, physical agents, and C1 esterase inhibitor deficiency

- Airway management

- Antihistamines

- Cool compresses

- Avoid triggers

- Pts with C1 esterase inhibitor deficiency: Acute management with androgens and long term therapy with C1 esterase inhibitor concentrate, antifibrinolytics, and icatibant

- Icatibant: Bradykinin receptor antagonist

- Derm findings: Generalized pruritic erythema involving 90% BSA 

- Presentation: Fever, malaise, and excessive vasodilation

- Vasodilation --> Protein and fluid loss --> Hypotension, electrolyte imbalance, and CHF

- Etiology: 50% due to pre-existing dermatoses

- Supportive care

- Search for underlying causes --> Treat

- Look for signs of secondary infection

- 18% mortality after treatment

- Autoimmune disease attacking desmoglein 3 --> Cell-cell desmosomes

- Epidermal break at the granulosum layer

- Causes flaccid blisters that easily rupture

- IF pattern: Web-like pattern

- Autoimmune disorder producing autoantibodies against collagen 17 and plakins --> Lamina lucida of BM

- Epidermal break at basal layer --> Tense blisters

- IF pattern: Linear pattern along the DEJ

- Direct IF: Skin taken from patient and incubated with fluorescence-labled anti-IgG, anti-IgM, or anti-C3-IgG

- Indirect IF: Serum is taken from patient and incubated with normal skin --> Incubate with flourescence-labeled anti-IgG, anti-IgM, or anti-C3-IgG

- Autoimmune disorder producing autoantibodies to collagen 7 of the anchoring fibrils

- Skin break below the lamina densa

- Lesions heal with scarring

- Differentiate from BP via the salt split skin IIF technique

- Deeper scarring tends to heal in milia

- Autoimmune disorder producing autoantibodies to desmoglein 1 in desmosomes

- Epidermal break higher than pemphigus vulgaris

- IF pattern: Lacy/Web-like pattern

- Congenital condition with easy blistering upon minor trauma or friction

1. Dystrophic: Collagen 7 mutation in anchoring fibrils --> Leads to severe scarring

- Deeper scarring tends to heal in milia

2. Simplex: Keratin 5 or 14 mutation in the basal keratinocyte later --> No scarring but basal epidermal break

- Keratin 5 and 14 are intracellular cytoskeletal components --> No associated autoimmune disease

3. Junctional: Collagen 17, A6/B4 integrin, or laminin 5 mutation --> Variable severity --> Split at DEJ

- Staph. aureus and Strep. infections

- Yellow crusts seen on lesions

1. Bullous form: Infection with exotoxin producing S. aureus --> Exfoliative toxins attacking desmoglein 1

- Most commonly affects children

- Face, extremities, trunk, buttocks, and perineum

- Can lead to SSSS if toxin gets into the blood stream

2. Non-bullous form: S. aureus or S. pyogenes infection

- Most common in neonates

- Face and extremities

- Honey-crusted erythematous patches/plaques with pustules

- Same epidermal split as in PF --> Upper epidermal layer

- Systemic lupus with autoantibodies against desmoglein 1

- Combination of lupus and pemphigus foliaceous

- More common in patients already diagnosed with systemic lupus (SLE)

- Initial lupus causes cell rupture and death

- PE develops due to lupus and individual propensity to develop autoantibodies --> Intracellular antibodies

- Antibiotics --> Bullous impetigo and SSSS

- Hereditary Epidermolysis Bullosa --> Avoid trauma, wound care, nutritional support, and possible gene therapy

- Autoimmune bullous disorders --> Reduce auto-antibodies --> High dose prednisone, azathioprine, mycophenolate, plasmapheresis, immunoabsorption, rituximab, and high dose IVIG

- Rituximab --> Anti-CD20 --> Kills off B-cells but autoantibodies still circulate for 3-4 weeks

- Acanthosis nigricans

- Diabetic dermopathy

- Bullosis diabeticorum

- Necrobiosis lipoidica

- Diabetic foot ulcers

- Eruptive xanthoma

- Yellow discoloration

- Necrolytic Migratory erythema

- Diabetic cutaneous disease

- 1-3% of diabetics --> 20-35% with NLD have diabetes

- Red-brown papules --> Well defined yellow-brown atrophic plaques with irregular violaceous borders and telangiectasias

- Most commonly found on the shins

- 35% ulceration

- Often painless

- Reddish yellow, pruritic and painful lesions

- Common in uncontrolled diabetics with hypertriglyceridemia

- Reduction of lesions through glucose and lipid reduction

- Familial hyper-lipoproteinemia (Type V) --> Genetic cause

- Most common on the back and extensor surfaces

- Can be present in diabetics or as a paraneoplastic syndrome in certain cancers

- Hyperpigmented velvety plaques found on areas of high friction

- Paraneoplastic type: Tripe palms --> Hyperpigmented/thick palms

- Neuroendocrine syndromes: Cushing's, Carcinoid, and glucogonoma syndrome

- Addison's disease

- Acromegaly

- Hypothyroidism: Myxedema

- Hyperparathyroidism: Calcinosis

- Hypoparathyroidism: Mucocutaneous candidiasis, Albright's hereditary osteodystrophy, pseudohypoparathyroidism, and pseudopseudohypoparathyroidism

- Polyostotic fibrous dysplasia: Melanotic macules

- Commonly seen pretibilally

- Yellow/redish plaques with massive swelling

- Associated with Hypothyroidism

- Associated with pseudopseudohypoparathyroidism

- Indurated plaques

- Very hard to treat

- IgG lambda overproduction due to tumors of monoclonal B-cells

- Purpuric lesions around the eyes --> Pinch purpura

- Blood vessels become so weak because of amyloid deposition

- Macroglossia and papules can also present around the eyelids and nasolabial folds --> Plasma cell and amyloid deposition

- Vesicles and bullae on sun-exposed areas --> Solitary

- Heals with scars and milia

- Hypertrichosis and fragile skin with sclerodermoid changes

- Porphyria Cutanea Tarda: Uroporphyrinogen decarboxylase deficiency in liver

- Risk factors: Alcoholism and hepatitis C infection

- Treatment: Phlebotomy and hydroxychloroquine (qlaquinil)/antimalarials

- Occurs in patients with chronic renal failure receiving maintanence hemodialysis

- Drugs-induced: Furosemide, nalidixic acid, tetracyclines and naproxen

- Normal porphyrin levels in urine, stool, and plasma 

- Henoch Schonlein Purpura: Associated with severe IgA nephropathy

- Dermatitis Herpetiformis: Associated with Celiac Disease --> IgA deposition in dermal papilla

- Inflammatory Bowel Disease

- Peutz Jeghers Syndrome

- Bowel by pass Syndrome

- Neutrophilic microabscesses in dermal papillae

- Granular IgA deposition in dermal papillae

- Derm presentation: Symmetric erosions and excoriations --> Pruritic

- Vesicles are rarely intact

- Increased risk of gastric lymphoma

- Single or multiple painful ulcers beginning as pustule and enlarge

- Undermined, boggy, violaceous border and surrounding edema

- Lesions may ulcerate down to fat or fascia

- May develop in sites of trauma

- Non-infectious

- Associated with inflammatory bowel disease, RA, monoclonal gammopathy, and malignancy

- Treatment: Steroids

- Multiple hamartomatous polyps on the tongue and fingers

- Also in the GI tract

- Increased incidence of visceral malignancies

- Autosomal dominant transmission --> STK11 mutation (chrom. 19)

- Pruritis

- Perforating dermatosis

- Calciphylaxis

- Nephrogenic Fibrosing Dermopathy

- Angiokeratomas/Fabry's Disease

- Henoch Schonlein Purpura

- Wegners granulomatosis (vasculitis)

- Associated with chronic renal failure

- Usually presents shortly before puberty

- Non-blanching, dark brown to red macules or papules

- Can present with corneal opacity, GI problems, tinnitus, and hearing loss

- Initially presents with burning pain on the palms as soles --> Fabry's crisis

- Prognosis: Death within 30-40 years

- Pathogenesis: Accumulation of glycolipids --> Renal and coronary disease and CVAs

- Alpha-galactosidase A deficiency --> X-linked lipid storage disease

- Vasomotor disturbances and labile hypertension due to ANS involvement

- Associated with glomerulonephritis

- Fevers

- Night sweats

- Fatigue

- Lethargy

- Loss of appetite

- Weight Loss

- Hypertension

- Proteinuria

- Renal failure

- Pulmonary hemorrhage

- c-ANCA positive

- Painless, nodular skin lesions --> Macules, papules or axillary freckles

- Initially appear on anterior chest --> Progressed to the whole body

- AD mutation in neurofibromin gene (Chrom. 17) in 2-10% of cases

- Associated symptoms: Bone deformities, acoustic neuromas, and meningiomas

- Ash-leaf hypopigmented macules

- AD mutation in TSC1 or TSC2

- Presents with mental retardation and seizures as well

- Periungual fibromas, subependymal nodules, and multiple renal angiomyolipomas possible

- Muir Torre Syndrome

- Cowden Syndrome

- Multiple neoendocrine neoplasia type 2B

- Reed's syndrome

- Gardners syndrome

- Howel-Evans syndrome

- Multiple leiomyomas of the skin and uterus

- Genetic origin

- Pruritic papular eruptions

- Most pronounced on arms and legs

- Possible renal cell cancer

- Heterozygous mutations in fumarate hydratase (FH) gene

- DNA mutation in mismatch repair --> MLH1 or MLH2 gene

- Internal malignancies --> Colon or GU cancers

- Sebaceous adenomas seen on the skin

- Mucosal and skin papules --> Benign

- Autosomal dominant disease --> Loss-of-function PTEN mutation (tumor suppressor gene)

- Predisposition to developing breast, thyroid, and endometrial cancer

- Presentation: Macrocephaly, intestinal hamartomatous polyps, benign skin tumors, and gangliocytoma of the cerebellum

- Erythema gyratum repens

- Dermatomyositis

- Signs of Lesser-Trelat

- Paraneoplastic pemphigus

- Hypertrichosis lanuginosa

- Acquired ichthyosis

- Acanthosis nigricans: Common present on the palms (tripe palms)

- Erythematous skin lesions

- Concentrically raised or serpiginous bands with desquamation

- Associated with lung, esophagus, and breast malignancies

- Greater risk of malignancy in patients over 40

- Occurs within the first 3 years of cancer diagnosis

- Women --> Ovarian and breast cancer

- Men --> Gastric cancer and lymphoma

- Can have muscle involvement and muscle weakness

- Small scaly papules on the fingers

- Generalized erythematous rash on the face

- Aldolase is a muscle enzyme similar to CPK used to diagnose

- Sudden eruption of brown papules

- Associated with GI and lymphoid malignancies

- Sudden increase in hair growth over a few months

- Intense growth of fine hair all over the body, including the face

- Association with colon and rectal cancer

- Kwashiorkor: Protein deficiency --> Edematous

- Marasmus: Severe malnutrition of proteins, fats, and carbs --> Emaciated

- Zinc deficiency: Erythematous scaly/yellow crusted plaques in the diaper and on the face

- Iron deficiency: Nail pitting

- Carotenemia: Excess B-caratene in the body --> Orange discoloration of the palms and tongue --> Rarely associated with hypothyroidism, diabetes, anorexia, liver disease, or kidney disease

- Pox-virus (dsDNA) infection --> Often asymptomatic

- Derm findings: Skin-colored papules (2-5mm) with central umbilication --> Solitary papules, no coalescence or erosions

- Commonly involved areas: Entire body --> Easily spread between body sites

- Transmission: Sexually or direct contact in children

- Incubation: 4-8 weeks

- HIV patients --> Multiple facial lesions

- Severe atopic dermatitis --> Multiple lesions

- Treatment: Curettage, liquid nitrogen, topical cantharidin, and immunomodulators

- Cantharidin: Induces blistering which separates the epidermis taking the virus with it when the skin sloughs off

- Over 100 genotypes identified

- HPV-1: Plantar and common warts

- HPV-6+11: Genital warts

- HPV-16+18: Cervical cancer

- Incubation: 6-18 months

- Transmission: During delivery, direct contact and fomites

- Histology: Acanthotic epidermis with papillomatosis, hyperkeratosis, and parakeratosis --> Prominent thrombosed capillary vessels (black dots) and large keratinocytes with an eccentric, pyknotic nucleus

- Diagnosis: Clinically

- Common warts/Verruca vulgaris: Sharply demarcated verrucous papules/nodules on the hands and fingers

- Flat warts/Verruca plana: Slightly elevated flat-topped papules on the face, hands and lower legs

- Plantar warts: Thick, enophytic, and hyperkeratotic papules

- Anogenital warts/Condylomata acuminate: Exophytic, cauliflower-like lesions

- Common feature is loss of skin lines due to wart growth

- Podofilox

- Imiquimod

- Podphyllin

- Cryotherapy --> 60-90% cure rate wth 20-40% recurrence rate

- Electrodesiccation and curettage

- CO2 laser

- Pulse dye laser and intralesional belomycin

- Vaccine: Gardasil (HPV-6,11,16,and 18)

- HSV-1: Oral and HSV-2:Genital

- Neonatal: 80% due to HSV-2 --> Acquired through delivery and 60% mortality rate for disseminated disease

- Derm findings: Multiple grouped vesicles than coalesce and rupture to form scalloped erosions

- Preceeded by prodrome, tingling and pain

- High mortality for disseminated disease

- Diagnosis: Tzanck smear test --> Multinucleated keratinocytes

- Treatment: Acyclovir, valcyclovir, and famcyclovir

1. Gingivostomatitis: Herpes infection that involves the entire oral mucosa

- Primarily in children

- VERY painful

- Fever, myalgias, inability to eat, and cervical adenopathy

2. Eczema Herpeticum: Herpes infeciton that spreads to the body folds

- Associated with atopic dermatitis

3. Herpetic whittlow: Herpes infection involving the fingers

4. Complications: Aseptic meningitis, encephalitis, and ocular involvement leading to blindness

- Ulcerated form of non-bullous impetigo

- S. pyogenes infection --> Primary or superinfection

- May result in post-streptococcal glomerulonephritis in some cases

- Culture

- Antibiotics: Topical mupirocin 2% then B-lacatamase-resistant penicillin

- Ecthyma infection: B-lactamase-resistant penicillin or first generation cephalosporin

- Folliculitis: Inflammation limited to the superficial aspect of the follicle

- Furuncle/Boil: Deeper involvement of the follicle with inflammatory cells --> Suppurative nodule with central necrotic plug

- Carbuncle: Coalescence of inflammed follicles

- Abscess: Fluctant warm and tender nodule

- Impetigo

- Management: Culture, warm compresses, incision and drainage, and systemic antibiotics

- Unilateral, poorly demarcated expanding erythema

- Warmth (calor), redness (rubor), pain (dolor), and induration (tumor)

- Face and lower extremities are most commonly affected

- Infection of the deep dermis and subcutis

- Causative agents: Group A strep, S. aureus, H influenza type B, group B strep (newborns), Strep. pneumo, and Staph. epidermidis

- Often polymicrobial if present in diabetics

- Management: Immobilization and elevation, board spectrum antibiotics, wound care, and treat underlying conditions

- Caused by exotoxin A production by S. aureus or S. pyogenes

- Conjunctival hyperemia, toxic palmar erythema and edema

- Multisystemic illness --> Fever, hypotension, GI symptoms (diarrhea), renal failure, and hepatitis

- May occur via the skin, vagina, or pharynx

- Exotoxin A is a superantigen --> Binds MHCII on T cells, activating T-cells

- Up to 20% of the body's T-cells become activated at one time!!

- Due to Corynebacterium species infection

- Derm findings: Pink/red erythematous patch --> Scale not typically present

- Typical areas of involvement: 4th toe web space, axilla, groin, or scrotum --> Moist, intertriginous areas

- Risk factors: Moisture, obesity, diabetes, and immunosuppression

- Diagnosis: Bright coral-red fluorescence with Woods lamp

- Management: Topical clindamycin, erythromycin, or 10-20% aluminum chloride

- Due to N. gonorrhoeae infection

- Symptoms: Fever, chills, polyarthralgia, and tenosynovitis

- Derm findings: Papules, pustules, and vesicles on palms, soles, and periarticular

- Eruptions may become hemorrhagic

- Reccurent infections: Late complement (C5-C9) deficiency

- Treatment: IV ceftriaxone, penicillin G, or chloramphenicol

- T. pallidum infection --> Spirochete

1. Primary chancre: Painless, presents  18-21 days after infection --> Unilateral or bilateral, non-suppurative with regional lymphadenopathy

- Extragenital chancres are possible

2. Secondary syphillis: Skin manifestations occuring in 80% of patients --> Presents on the hands, face, and body, extremely contagious

- Copper colored with white scale --> Annular papules/plaques

- Rash lasts several weeks to months

- 25% of patients have rash relapses

- Prodrome: Weight loss, low grade fever, malaise, headache, sore throat, arthralgias, etc

- Can present on mucosal surfaces or on the scalp (moth-eaten hair loss)

3. Tertiary: High cellular immune reactivity to organism

- Gumma formation in skin, bones, CNS, heart and great vessels

- Skin biopsy

- Primary serology: Non-specific (RPR and VDRL) and specific (MHA-TP and FTA-ABS)

- Antibiotics: Penicillin G and tetracyclines as second line therapy

- Jarisch-Herxheimer Reaction: Fever, etc after antibiotic initiation --> Systemic response to dying spirochetes

- Borrelia specious infection from tick bite

- Clinical marker: Erythema migrans behind the knee, axilla, and groin

- Flu-like illness common

- If untreated --> Neuro, CNS and joint manifestations

- AV block and myocarditis are possible

- Serology: Immunoflourescence and the western blot to determine prescence of disease

- Treatment: Doxycycline or penicillin in children under 8 years old

1. Tinea versicolor: Malassezia furfur/P. ovale infection --> Hypopigmented lesions that coalesce to form large patches

- Treatment: Topical imidaxole or selenium sulfide shampoo

2. Candidiasis: C. albicans infection in the skin folds --> Red satallite macules seem

- Treatment: Topical nystatin or clotrimazole or oral fluconazole, etc

3. Dermatophyte Infections --> Trichophyton, microsporum, or epidermophyton infections --> Ingest keratin in the stratum corneum, hair, and nails

- Tinea capitis: Hair loss and inflammatory scalp plaques

- Tinea corporis/Ringworm: Annular sclaing plaques with central clearing and mild itching

- Onychomycosis: Yellowed and thickened nails --> Commonly seen with tinea pedis

- Tinea pedis/Athlete's foot

- Treatment: Oral antifungals and topical antifungals depending on presentation