Skin Across the Lifespan Notes PDF

**Skin Across the Lifespan** **Infant/Child** - Smoother than adults, less hair - Ratio of skin surface area to body volume is larger than adults - Water content is higher (*more likely to be dehydrated*) - Melanin reaches adult levels by 1 years old - Sebaceous glands stop producing...

**Skin Across the Lifespan** **Infant/Child** - Smoother than adults, less hair - Ratio of skin surface area to body volume is larger than adults - Water content is higher (*more likely to be dehydrated*) - Melanin reaches adult levels by 1 years old - Sebaceous glands stop producing between 6-12 months; becomes more active around 7 years old **Adolescents** - Apocrine glands enlarge and become active during puberty - Sebaceous glands increase sebum production in response to increased hormone levels (primary - Androgen) - Hair growth responds to androgen levels (axillae, pubic, facial - boys) **Pregnant Women** - Increased blood flow to skin - hands and feet due to increased number of capillaries and vasodilation - Acceleration of sweat and sebaceous gland activity - May develop vascular spiders and hemangiomas - Skin thickens and fat deposited in the subdermal layers - Increased pigmentation - face, nipples, areolae, axillae, perianal skin, and umbilicus **Older Adults** - Sebaceous and sweat gland activity decreases resulting in dryer skin, less perspiration - Epidermis thins and flattens - Vascularity of the dermis decrease - Epidermal permeability is increased - Dermis becomes less elastic - loss of collagen and elastic fibers and shrinks; epidermis to fold and wrinkle - Gray hair = \# of functioning melanocytes decreases **Age Related Changes** **Hair** - Progressive hair loss occurs after age 40 - Male pattern baldness is a *inherited trait* that is mediated by ***testosterone*** - Hair changes - from darker, thicker, and more numerous to lighter to thinner, and less numerous with aging **Nails** - Dull, brittle, hard, and thick with aging due to diminished vascular supply to nail bed - Increase in longitudinal striations - can cause splitting of nail surface - Toenails may have hyperkeratosis and resultant thickening (*onychomycosis*) **Glands** - Sebaceous glands show functional decline with a decrease in sebum secretion - Decrease in sebum secretion and in the number of sebaceous glands = drier and coarse skin - Sweat glands generally decrease in size, number, and function - Alterations in skin disorders and/or hair growth may be attributed to skin car and/or hair care practices: - Tight braids or ponytails may cause ***traumatic alopecia*** - Products or practices utilized may contribute to skin irritations - Important to note that skin vaies in its mormal presentation depending on pigmentation: - **Light skin:** more susceptible to skin changes/disorders related to sun exposure (*freckles, squamous and basal cell carcinoma, psoriasis, senile keratosi*s) - **Dark skin**: more susceptible to hypopigmentation and hyperpigmentation - lesions (erythema) may not be easily seen - Seborrheic dermatitis and keloids are seen more often in African Americans - Mongolian spots more prominent in babies with darker skin **Assessment of the Integumentary System** - Examination consists of: - Lesion, size, color, symmetry, shape, number, distribution, including primary and secondary lesions - **Primary lesions** - original appearance - **Secondary lesions** - appearance modified by normal progress over time or by such external agents as scratching (e.g., chicken pox) - Assess family/personal history, geographic origin, present abode, season, occupation, leisure activity, any diseases, previous treatment, special history Terms for Skin Lesions (Table 25.1) - **Excoriation** - traumatic lesion breaking the epidermis and causing a raw linear defect (i.e., deep scratch); often self-induced. - **Lichenification** - thickened, rough skin (similar to lichen on a rock); usually the results of repeated rubbing. - **Macule, patch** - circumscribed, flat lesion distinguished from surrounding skin by color. Macules are 5 mm in diameter or less; patches are greater than 5 mm. - **Onycholysis** - Separation of nail plate from nail bed. - **Papule, Nodule** - Elevated dome-shaped or flat-topped lesion. Papules are 5 mm or less across; nodules are greater than 5 mm in size. - **Plaque** - Elevated flat-topped lesion, usually greater than 5 mm across (may be caused by coalescent papules).\ **Pustule** - Discrete, pus-filled, raised lesion. - **Scale** - Dry, horny, plate-like excrescence; usually the result of imperfect cornification. - **Vesicle, Bulla, Blister** - Fluid-filled raised lesion 5 mm or less across (vesicle) or greater than 5 mm across (bulla). Blister is the common term for either lesion. - **Wheal** - Itchy, transient, elevated lesion with variable blanching and erythema formed as the result of dermal edema - **Acanthosis** - Diffuse epidermal hyperplasia - **Dyskeratosis** - Abnormal, premature keratinization within cells below the stratum granulosum. - **Erosion** - Discontinuity of the skin showing incomplete loss of the epidermis. - **Exocytosis** - Infiltration of the epidermis by inflammatory cells. - **Hydropic swelling (ballooning)** - Intracellular edema of keratinocytes, often seen in viral infections. - **Hypergranulosis** - Hyperplasia of the stratum corneum, often associated due to intense rubbing - **Hyperkeratosis** - Thickening of the stratum corneum, often associated with a qualitative abnormality of the keratin. - **Lentiginous** - Linear pattern of melanocyte proliferation within the epidermal basal cell layer. - **Papillomatosis** - Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae. - **Spongiosis** - Intercellular edema of the epidermis. - **Ulceration** - Discontinuity of the skin marked by complete loss of the epidermis revealing dermis or subcutis. - **Vacuolization** - Formation of vacuoles within or adjacent to cells; often refers to basel cell-basement membrane zone area. - Repair (healing) refers to the restoration of tissue architecture and functions after an injury. - Repair occurs by two processes: regeneration and scarring - **Regeneration** - tissues can replace the damaged components and essentially return to a normal cellular state - **Connective tissue deposition (scar formation)** - injured tissues are incapable of regeneration, or if the supporting structures of the tissue are too severely damaged to support regeneration of the tissue cells, repair occurs by the laying down of connective (fibrous) tissue. - Regeneration of injured cells and tissues involved cell proliferation. - Driven by growth factors and is critically dependent on the integrity of the extracellular matrix (ECM), and by the development of mature cells from tissue stem cells. - Tissues are classified as *labile, stable, and permanent,* according to the proliferative capacity of their cells. - Continuously dividing tissues (labile tissues) contain stem cells that differentiate to replenish lost cells and maintain tissue homeostasis. - Cell proliferation is controlled by the cell cycle and is stimulated by growth factors and interactions of cells with the ECM. Example: Liver Regeneration - classic example of repair by regeneration - Triggered by cytokines and growth factors produced in response to loss of liver mass and inflammation - Regeneration may occur by proliferation of surviving hepatocytes or repopulation from progenitor cells - Restoration of normal tissue structure can occur only if the residual tissue is structurally intact **Connective Tissue Deposition** - Tissues are repaired by replacement with connective tissue and scar formation if the injured tissue is not capable of proliferation or if the structural framework is damaged and cannot support regeneration. - Main components: angiogenesis, migration and proliferation of fibroblasts, collagen synthesis, and connective tissue remodeling - Repair starts with the formation of granulation tissue and culminates in the laying down of fibrous tissue - Multiple growth factors stimulate the proliferation of the cell types involved in repair. - TCG-β is a potent fibrogenic agent; ECM deposition depends on the balance between fibrogenic agents, metalloproteinases (MMPs) that digest ECM, and TIMPs - **Primary closure** - edges of incision are closely opposed (e.g., sutures, staple, or taping, to allow healing by injury intention - **Secondary closure** - incision left open and heals by secondary intention as new tissue infills from the base and sides of the wound (will scar) - **Delayed primary closure** - incision left open for several day and sometimes weeks, allowing treatment of infection/contamination, removal of nonviable tissue, and/or for resolution of swelling, before proceeding to primary closure or closure with a *flap/graft* - **Venous leg ulcers** - develops mostly in elderly people as a result of chronic venous hypertension. These ulcers fail to heal because of poor delivery of oxygen to the site of the ulcer - **Arterial ulcers -** develop in those with atherosclerosis of peripheral arteries, especially with diabetes - Ischemia results in atrophy → necrosis; these lesions are painful - **Diabetic ulcers** - affects lower extremities (feet); tissue necrosis and failure to heal as a result of vascular disease causing ischemia, neuropathy, systemic metabolic abnormalities, and secondary infections - These lesions are characterized by ***epithelial ulceration and extensive granulation tissue*** in the dermis. - **Pressure sores -** skin ulceration and necrosis of underlying tissues caused by prolonged compression of tissues against a bone; the lesions caused by mechanical pressure and local ischemia. - **Hypertrophic scars** - accumulation of excessive amounts of collagen may give rise to a raised scar known as a hypertrophic scar; they ***grow rapidly*** and contain abundant myofibroblasts, but they ***tend to regress over several months***. - **Keloid** - scar tissue that grows beyond the boundaries of the original wound and ***does not regress***; keloid formation seems to be an individual predisposition, and common in black populations - **Mechanical Trauma** - type of injury depends on the shape of the colliding object, amount of energy discharged at impact, and the tissues or organs that bear the impact - Soft tissues react similarly to mechanical forces, patterns of injury can be divided (abrasions, contusions, lacerations, incised wounds, and puncture wounds) - **Thermal Injury -** injury depends on factors (depth of burns, percentage of body surface, internal injuries causes by inhalation of hot toxic fumes, promptness and efficacy of therapy, especially fluid and electrolyte management and prevention/control of wound infections) - **Superficial burns (1st degree burns)** - confined to the epidermis - **Partial - thickness burns (2nd degree burns)** - injury to dermis - **Full - thickness burns (3rd degree burns)** - burns to the subcutaneous tissue - *White or charred, dry, and painless (due to destruction of nerve endings), whereas, depending on the depth, partial-thickness burns are pink or mottled with blisters and are **[painful]**; tissue reveals coagulative necrosis, adjacent to vital tissue that quickly accumulates inflammatory cells and marked exudation* - Burn Shock - Patho: capillary leak occurs within minutes and persists for 24 hours - Fluid lost in the area of the burn and internally collects in nearby soft tissues causing interstitial edema - Rate and volume of fluid lost directly related to severity of burn - Parkland formula - estimation of burn injury dictates fluid resuscitation **Shock, sepsis, and respiratory insufficiency are the greatest threats to life in burn patients. Particularly in burns of more than 20% of the body surface, there is a rapid (within hours) shift of body fluids into the interstitial compartments throughout the body due to the systemic inflammatory response syndrome, leading to shock** **Cardiovascular Dysfunction** - Often accompanied by significant drop in cardiac output that does not parallel gradual reduction in blood volume and is refractory to restoration of the circulating volume - Pathophysiologic mechanism is poorly understood but involvement of metabolic and immunologic factors is suggested **Respiratory Dysfunction** - Result of obstruction, interstitial alterations, and metabolic changes - Inhalation injury results in chemical denaturing of pulmonary tissue and edema - Acute respiratory distress syndrome (ARDS) usually seen within 6 days **Renal Dysfunction** - Early renal failure develops within first 5 days post burn, due to low intravascular volume and presence of myoglobin (rhabdomyolysis; can cause kidney failure) - Late renal failure (\>5 days postburn) from sepsis, or use of nephrotoxic medications **Metabolic Changes** - Massive release of catecholamines: hypermetabolism manifests as tachycardia and increased oxygen consumption - Accelerated protein breakdown leads to muscle protein wasting **Cellular Changes** - Cell membrane transport defect related to alteration in the steady-state composition, characterized by high intracellular concentrations of sodium (sick cell syndrome) - Decrease in the efficiency of the sodium-potassium pump; diminished membrane potential (calcium channels disrupted) **Immune Response** - Burns suppress immune system making infections possible - Cytokines act directly on burn wound; activate agents that release oxidants, arachidonic acid metabolites and proteases; further local and systemic inflammation; multisystem organ failure - As a result of vascular changes, fluid and fibrinogen leave the dilated, permeable vessels; leads to burn shock +-----------------+-----------------+-----------------+-----------------+ | **BURNS** | **1st Degree** | **2nd Degree** | **3rd Degree** | | | | | | | | **(SUPERFICIAL) | **(PARTIAL | **(FULL | | | ** | THICKNESS)** | THICKNESS)** | +-----------------+-----------------+-----------------+-----------------+ | Area | ***ONLY | ***Epidermis to | ***Epidermis, | | | superficial | the level of | dermis, and | | | tissue*** | the dermis*** | underlying | | | destruction of | | subcutaneous | | | outermost | | tissue*** | | | layers of the | | | | | epidermis | | | +-----------------+-----------------+-----------------+-----------------+ | Signs/symptoms | Local | Moist, | Appear white, | | | discomfort, | thin-walled | cherry red, or | | | erythema, | blisters with | black, with | | | headache, | pain | deep blisters; | | | chills, N/V | | ***painless*** | | | | Mottled | areas | | | | appearance: | | | | | large areas of | | | | | waxy-white | | | | | tissue | | | | | surrounded by | | | | | light pink or | | | | | red tissue, | | | | | blisters flat | | | | | and dry | | +-----------------+-----------------+-----------------+-----------------+ | Healing | Typically | Injuries heal | Wound has dry, | | | self-limiting | 3-4 weeks; | hard, leathery | | | healing in 3-6 | absence of | texture | | | days | infection | | +-----------------+-----------------+-----------------+-----------------+ | Treatment | In infants and | Hair typically | Often | | | elderly may | reappears in | necessitate | | | require IV | 7-10 days in | escharotomies | | | resuscitation | less severe | or fasciotomies | | | to treat | burns | to restore | | | dehydration | | distal | | | | | circulation | +-----------------+-----------------+-----------------+-----------------+ - **Electrical Injury** - related to subsequent tissue damage as electrical energy is converted to heat - **Incidence Mortality** - Classified as high (1000 volts or greater - high-tension sources)) or low voltage (household currents) - Lightning carries a direct current of 100 million or more volts; may injure by direct stroke or side flash - Type of injury and the severity and extent of burs depend on the strength (amperage), duration, and path of the electric current within the body. - Two types of injuries: - 1\. Burns - 2\. Ventricular fibrillation or cardiac and respiratory center failure - disruption of nerve impulse conduction - **Arcing electricity**: heat injury, current does not travel through body - True electrical injury involves a *current entering the body*, traversing a portion of the body, and *exiting at another body site*; usually classified as ***fourth-degree injury*** - Voltage, type of current (direct or alternating) and length of contact influence damage - High voltage AC or DC most damaging - Manifestations: - Produces entrance wound and at least one exit wound - Current rarely produces direct visceral damage but severe injuries to extremities are common; amputation rate \> 90% - Heat coagulates blood vessels; arrhythmias or cardiac arrest, metabolic acidosis, myoglobinuria - Injury by ionizing radiation - **Heat cramps** - result from loss of electrolytes via sweating. Cramping of voluntary muscles, usually in association with vigorous exercise, is the hallmark. - **Heat exhaustion** - onset is sudden, with prostration and collapse, and results from a failure of the cardiovascular system to compensate for hypovolemia caused by dehydration. Resolves if the rehydration occurs. - **Heat stroke** - is associated with high ambient temperatures, high humidity, and exertion. Older adults, individuals undergoing intense physical stress, and persons with cardiovascular disease are at particularly high risk for heat stroke. - Thermoregulation mechanisms fail, sweating ceases, and the core body temperature rises to more than 40C, leading to multiorgan dysfunction that can be rapidly fatal. - Accompanied by marked generalized vasodilation, with peripheral pooling of blood and a decreased effective circulating blood volume. - Hyperkalemia, tachycardia, arrhythmias, and other systemic effects are common. Particularly important, however, are sustained contractions of skeletal muscle that can exacerbate the hyperthermia and lead to muscle necrosis (rhabdomyolysis) - Prolonged exposure to low ambient temperature leads to hypothermia, a condition seen all too frequently in homeless people. - High humidity and wet clothing, sometimes exacerbated by dilation of superficial blood vessels due to ingestion of ETOH, hastens the lowering of body temperature. - Body temperature of 90F, loss of consciousness occurs, followed by bradycardia and atrial fibrillation at lower core temperature. - Hypothermia causes injury by two mechanisms: - 1.Direct effects are probably mediated by physical disruptions within cells by high salt concentrations caused by the crystallization of intracellular and extracellular water (frostbite). - 2\. Indirect effect results from circulatory changes, which vary depending on the rate and duration of permeability, leading to edema and hypoxia **Disorders of Pigmentation and Melanocytes** - Freckles - Generally small (1mm to several mm in diameter) - Tan-red or light brown macules that appear after sun exposure - Hyperpigmentation of freckles results from increased amounts of melanin pigment within basal keratinocytes - Associated melanocytes may be slightly enlarged but are normal in density - No change in number of melanocytes nut in the degree of pigmentation - Once present, freckles fade and darken in a cyclic fashion during winter and summer - Lentigo - Common benign localized hyperplasia of melanocytes - Occurs at all ages, but most commonly appears in infants and children - There is no sex or racial predilection - Cause and pathogenesis are unknown - May involve mucous membranes as well as the skin and consist of small (5-10 mm across), oval, tan-brown macules or patches - Histologic feature is ***linear (nonested) melanocytic hyperplasia*** restricted to the cell layer immediately above the basement membrane that produces a hyperpigmented basal cell layer - Unlike freckles, lentigines ***do not darken*** ***when exposed to sunlight*** - Melanocytic Nevus - Common benign neoplasms are caused in most cases by acquired activating mutations in components of the RAS signaling pathway. - Acquired mutations that lead to constitutive activation of RAS or the serine/threonine kinase BRAF - Tan to brown, uniformly pigmented, small (usually less than 6 mm across), relatively flat macules or elevated papules with well-defined, rounded borders. - **Junctional nevi** - early lesion, small, ***flat***, symmetric, and uniform; aggregates or nests of round cells that grow along the dermoepidermal junction - **Compound nevi** - junctional nevi form into compound nevi; grows in the underlying dermis as nests or cords of cells - Dysplastic Nevi - Can be direct precursors of melanoma and when multiple in number are a marker of an increased risk for melanoma - May be isolated - risk of malignant transformation is very low - Acquire activating mutations in the *NRAS* and *BRAF* genes - Inherited loss-of-function mutations in *CDKN2A* - RAS or BRAF activation and increased CDK4 activity contribute to the development of dysplastic nevi - Larger than most acquired nevi (often greater than 5 mm across) - May appear as flat macules, slightly raised plaques with a "pebbly" surface, or target-like lesions with a darker raised center and irregular flat periphery - Diagnostic architectural feature: coalescent intraepidermal nests - Cytologic feature: cytologic atypia - Clinical significance potential marker or precursor of melanoma - Can occur on the sun exposed and protected body surfaces - Melanoma - Common neoplasm that can be cured if it is detected and treated when it is in its earliest stages. - Melanoma arises in the skin; other sites of origin include the oral and anogenital mucosal surfaces (i.e., oropharynx, gastrointestinal and genitourinary tracts), the esophagus, the meninges, and the uvea of the eye - 10-15% of affected patients, the risk of melanoma is inherited as an autosomal dominant trait with variable penetrance - Most deadly of all skin cancers and is strongly linked to acquired mutations caused by exposure to UV radiation in sunlight. - Normally seen on left side, i.e., driving - Toenail - aggressive - Familial cases are associated with germline mutations affecting genes that regulate cell cycle progression (disrupt cell cycle control genes and activate pro-growth signaling pathways), whereas others are associated with germline mutations affecting telomerase expression - Remaining patients: melanoma is sporadic and strongly related to a single predisposing environmental factor: UV radiation exposure from sunlight - Variations in color, appearing in shades of black, brown, red, dark blue, and gray - May have zones of white or flesh-colored hypopigmentation sometimes due to focal regression of the tumor - The borders of melanomas are irregular and often notched - Clinical features: The most important warning signs, sometimes called the ABCDEs of melanoma, are (1) asymmetry; (2) irregular borders; and (3) variegated color; (4) increasing diameter; and (5) evolution or change over time, especially if rapid. - 6 mm or greater is CONCERNING - Examples - tanning bed exposure, sunburn, and peeling - Pathways important in melanoma. Growth factors activate signaling circuits involving receptor tyrosine kinases, RAS, and two key downstream pathways that include serine/threonine kinase BRAF and the phospholipid kinase P13K. - The most frequent "driver" mutations in melanoma affect cell cycle control, pro-growth pathways, and telomerase. - Typically has a superficial spreading-radial growth phase and then shifts to a vertical growth phase during which the tumor cells invade downward into the deep dermis as an expansile mass. Vertical growth phase is often heralded by the appearance of a nodule and correlates with the emergence of a tumor subclone with metastatic potential. Seborrheic Keratosis - - - - - - Acanthosis Nigricans - Important cutaneous sign of several underlying benign and malignant conditions - Thickend, hyperpigmented skin with a velvet-like texture that most commonly appears in the flexural areas (axillae, skin folds of the neck, groin, and anogenital regions) - In at least 80% of cases, acanthosis nigricans is associated with benign conditions and develops gradually - In the remaining cases, acanthosis nigricans arises in association with cancers - The unifying feature in all types of acanthosis nigricans is a disturbance that leads to increased growth factor receptor signaling in the skin. - Familial form is associated with germline activating mutations in the receptor tyrosine kinase FGFR3 - Type 2 diabetes, hyperinsulinemia, is believed to provoke increased stimulation of insulin-like growth factor receptor-1 (1GFR1), another receptor tyrosine kinase that activates the same signaling pathways as FGFR3 - Usually seen during childhood or puberty. - It may occur (1) as an autosomal dominant trait with variable penetrance, (2) in association with obesity or endocrine abnormalities (particularly with pituitary or pineal tumors, or with diabetes), and (3) as part of several rare congenital syndromes. The most common associations are with ***obesity and diabetes.*** - In the remaining cases, acanthosis nigricans arise in association with cancers, most commonly gastrointestinal adenocarcinoma, usually in middle-aged and older individuals. In this setting, acanthosis nigricans is best viewed as a paraneoplastic phenomenon that is likely caused by growth factors released from tumors. Fibroepithelial Polyp (skin tag) - Other names - acrochordon, squamous papilloma, skin tag - Benign epithelial tumor - One of the most common cutaneous lesions - Usually found on neck, trunk, face, and intertriginous areas - Middle-aged to older adults - Soft, flesh-colored, bag-like tumors that are often attached to the surrounding skin by a slender stalk - More prominent during pregnancy because of hormonal stimulation Epithelial or Follicular Inclusion Cyst - Benign epithelial tumor - Common lesions formed by the invagination and cystic expansion of the epidermis or, perhaps more commonly, a hair follicle - Large, they may be subject to traumatic rupture, which can spill keratin into the dermis and lead to an extensive and often painful granulomatous inflammatory response **Premalignant and Malignant Epidermal Tumors** Actinic Keratosis - Usually occurs in sun-damaged skin and exhibits hyperkeratosis - May show progressively worsening dysplastic changes that culminate in cutaneous squamous cell carcinoma - Usually less than 1 cm in diameter - Typicaly, tan-brown, red, or skin-colored and have a rough, sandpaper-like consistency - Some lesions produce so much keratin that a "cutaneous horn" develops - Sun-exposed sites (face, arms, dorsum, of hands) are most frequently affected - They may regress or remain stable throughout life, but enough transform to malignancy that local eradication (gentle curettage, freezing, or topical application of chemotherapeutics agents) is warranted. Squamous Cell Carcinoma - Second most common tumor arising on sun-exposed in older people, only by basal cell carcinoma - Higher in men - Lesions are nodular and ulcerated - Invasive squamous cell carcinomas are usually discovered while they are small and resectable. - Less than 5% of these tumors metastasize to regional nodes; these lesions are generally deeply invasive and involve the subcutis - Most important cause of cutaneous squamous cell carcinoma is DNA damage induced by exposure to UV light - Incidence is proportional to the degree of lifetime sun exposure - P53 dysfunction is an early event in the development of tumors induced by sunlight Basal Cell Carcinoma - Locally aggressive cutaneous tumor that is associated with mutations that activate the ***Hedgehog*** signaling pathway - Most common invasive cancer in humans; slow-growing tumors that rarely metastasize - Vast majority are recognised at an early stage and cured by local excision - Occurs at sun-exposed sites in lightly pigmented elderly adults - Usually present as ***pearly papules*** containing prominent dilated subepidermal blood vessels (**telangiectasias)** - Advanced lesions may ulcerate, and extensive local invasion of bone or facial sinuses may occur after many years of neglect or in unusually aggressive tumors **Tumors of the Dermis** Benign Fibrous Histiocytoma (Dermatofibroma) - Heterogeneous family of morphologically and histogenetically related benign dermal neoplasms of uncertain lineage - Seen in adults and often occur on the *legs of young and middle-aged women*. Lesions are asymptomatic or tender and *may increase and decrease slightly in size over time.* - Exact etiology remains a mystery; possibly *trauma* - Appear as firm, tan to brown papules - Most are less than 1 cm in diameter, but actively growing lesions may reach several cm in diameter; with time they often become flattened Dermatofibrosarcoma Protunerans - Well-differentiated, primary fibrosarcoma of the skin - Slow growing, and although locally aggressive and can recur, they rarely metastasis - Molecular hallmark of dermatofibrosarcoma protuberans is a translocation involving the genes encoding collagen 1A1 (*COL1A1)* and platelet-derived growth factor-β (*PDGFB)* - *Usually appears as a "protuberant"* nodule, most often on the trunk, within a firm (indurated) plaque that may sometimes ulcerate - Composed of closely packed fibroblasts arranged radially, reminiscent of blades of a pinwheel, a pattern referred to as **[storiform]** **Mastocytosis** - Characterized by increased numbers of mast cells in the skin and, in some instances, in other organs as well - Cutaneous form of the disease that affects predominantly children and accounts for more than 50% of all cases is termed *urticaria pigmentosa* - Cutaneous lesions are usually multiple, although solitary mastocytomas may also occur in very young children - Usually in adults - 10% of individuals with mast cell disease have systemic disease, with mast cell infiltration of many organs - **Darier sign** **-** localized area of dermal edema and *erythema (wheal)* that occurs when lesional skin is runned - **Dermatographism** - an area of dermal edema resembling a hive that occurs as a result of localized stroking of apparently normal skin with a painted instrument - Systemic: pruritus and flushing, triggered by certain foods, temperature changes, alcohol, and certain drugs (morphine, codeine, aspirin) - Watery nasal discharge (rhinorrhea) - Rarely, gastrointestinal or nasal bleeding, possibly due to the anticoagulant effects of heparin - Bone pain - which may be caused by *mast cell infiltration* orby pathologic fractures stemming from osteoporosis **Acute Inflammatory Dermatoses** Urticaria (hives) - Common disorder of the skin that is usually caused by localized mast cell degranulation and is uniformly associated with dermal microvascular hyperpermeability - Produces pruritic edematous plaques called *wheals* - Urticaria most often occurs between ages 20-40, but all ages are susceptible - Lesions develop and fade within hours (usually less than 24 hours), and episodes may last for days or persist for months - Sites of for urticarial eruptions include any area exposed to pressure, such as the trunk, distal extremities, and ears - Commonly the result of antigen-induced release of vasoactive mediators from mast cells - *Mast cell--dependent, immunoglobulin E (IgE)--dependent*. - Urticaria of this type follows exposure to many different antigens (pollens, foods, drugs, insect venom) and is an example of a localized immediate hypersensitivity (type I) reaction triggered by the binding of antigen to IgE antibodies that are attached to mast cells through Fc receptors - *Mast cell--dependent, IgE-independent* - *This subset results from substances that directly incite the degranulation of mast cells, such as opiates, certain antibiotics, and radiographic contrast media.* - *Mast cell--independent, IgE-independent*. - These forms of urticaria are triggered by local factors that increase vascular permeability. One form is initiated by exposure to chemicals or drugs, such as aspirin, that inhibit cyclooxygenase and arachidonic acid production. The precise mechanism of aspirin-induced urticaria is unknown. A second form is hereditary angioneurotic edema (Chapter 6), caused by an inherited deficiency of C1 inhibitor that results in excessive activation of the early components of the complement system and production of vasoactive mediators. Acute Eczematous Dermatitis - Eczematous dermatitis typically results from T-cell mediated inflammatory reactions (type IV hypersensitivity) - 5 categories: 1. Allergic contact dermatitis - Results from external application of an antigen ***(e.g. poison ivy)*** or a reaction to an internal circulating antigen (ingested food or drug) - Typically results from t-cell mediated inflammatory reactions (type IV hypersensitivity) - Rhus dermatitis (poison ivy, oak, sumac) is the most common type of allergic contact dermatitis - Symptoms begin within 48 hours of contact; red, papulovesicular, crusted lesions in a sometime-linear pattern that can develop reactive **acanthosis** and **hyperkeratosis** and take on the appearance of raised scaling plaques - If the allergen remains on the skin, it can spread to non exposed areas. Exposure to blister fluid does not spread poison ivy lesions 2. Atopic dermatitis - Patho: Genetic defects in the epidermal barrier protein filaggrin have been cited as a major cause - The stratum corneum layers with this mutation (loss-of-function of filaggrin) have lower levels of natural moisturizing factor and are also deficient in extracellular lipids including ceramides. - Clinical manifestations: - Atopy: genetic component - Most common in children; usually improves with age - Lesions pruritic, oozing, crusting, coalescent papule; thickening of the skin or lichenification occurs - Atopic triad - asthma, allergies (allergic rhinitis/hay fever), conjunctivitis 3. Drug-related eczematous dermatitis 4. Photo Eczematous dermatitis 5. Primary irritant dermatitis Erythema Multiforme - Hypersensitivity reaction to certain infections and drugs - Individuals of any age and is associated with the following conditions: - 1\. Infections such as herpes simplex, mycoplasmal infections, histoplasmosis, coccidioidomycosis, typhoid, and leprosy - 2\. Exposure to certain drugs (sulfonamides, penicillin, barbiturates, salicylates, hydantoins, and antimalarials) - 3\. Cancer (carcinomas and lymphomas) - 4\. Collagen vascular diseases (lupus erythematosus, dermatomyositis, and polyarteritis nodosa) - Characterized by keratinocyte injury mediated by skin-homing CD8+ cytotoxic T lymphocytes - CD8+ cytotoxic T-cells and more prominent in the central portion of the lesions, while CD4+ helper T-cells and Langerhans cells are more prevalent in the peripheral portions - The epidermal antigens that are recognized by the infiltrating T-cells in erythema multiforme remain unknown - Diverse array of lesions (hence the term multiforme), including macules, papules, vesicles, bullar, and characteristic targetoid (target-like) lesions - Stevens-Johnson syndrome, which is often seen in children - Lesions involve not only on the skin but also the lips and oral mucosa, conjunctiva, urethra, genital, and perianal areas. Secondary infection of involved areas due to loss of skin integrity may results in life-threatening sepsis - Toxic epidermal necrolysis is characterized by diffuse ***necrosis and sloughing*** of cutaneous and mucosal epithelial surfaces. The widespread epidermal damage produces a clinical picture similar to patients with extensive burns Psoriasis - Chronic, inflammatory, autoimmune disorder that develops in response to environment and genetic factors, including particular HLA gene variants. Sensitized CD4+ T-cells lead to infiltration into the skin and overexpression of multiple cytokines, including tumor necrosis factor-ɑ (TNF) and various interleukins - Induces keratinocyte proliferation, resulting in the characteristic lesions - Most frequently affects elbow, knees, scalp, lumbosacral areas, intergluteal cleft, and glans penis - The typical lesion is well-demarcated, pink to salmon-colored plaque covered by loosely adherent silver-white scale - Auspitz sign - proximity of vessels within the dermal papillae to the overlying parakeratotic scale accounts for the characteristic clinical phenomenon of multiple, minute, bleeding points when the scale is lifted from the plaque - Inherited condition with immune system involvement - Lesions on knees, elbow, lower back, scalp, nails; exacerbation and remission - Psoriasis is one cause of total body erythema and scaling known as erythroderma. Nail changes occur in 30% of cases of psoriasis and consist of yellow-brown discoloration (often likened to an oil slick), with pitting, dimpling, separation of the nail plate from the underlying bed (onycholysis), thickening, and crumbling. Seborrheic Dermatitis - Unknown cause - Inflammation of the epidermis is not a disease of the sebaceous glands. - Classically involves regions with a high density of sebaceous glands, such as the scalp, forehead (especially the glabella), external auditory canal, retroauricular area, nasolabial folds, and presternal area - Thoughts of an inflammatory reaction to *Malassezia furfur* chronic infection (a yeast that is part of normal follicular flora) in lipid - dense area of the skin is responsible - Papulosquamous skin disease manifested by various degrees of scaling and erythema in areas of high oil gland concentration (scalp, eyebrows, eyelids, nasolabial folds, pinna, and posterior sulcus or ears) - ***Cradle cap (infants) and dandruff (adults)*** - Involvement of sebum is supported by clinical observations of patients with Parkinson disease, who typically show increased sebum production secondary to dopamine deficiency and have a markedly increased incidence of seborrheic dermatitis. Once treated with levodopa, the oiliness of the skin decreases and the seborrheic dermatitis improves Lichen Planus - Pathogenesis of lichen planus is not known. Expression of altered antigens in basal epidermal cells of the dermoepidermal junction elicits a cell-mediated cytotoxic (CD8+) T-cell response. - ***Pruritic, purple, polygonal, planar, papules, and plaques*** are the tongue-twisting *"six Ps"* of lichen planus, a disorder of skin and mucosa - Usually self-limited, most commonly resolving spontaneously 1-2 years after onset - Leaves a residual post-inflammatory hyperpigmentation - Oral lesions may persist for years. - As in psoriasis, the Koebner phenomenon may be seen in lichen planus. **Blistering (Bullous) Diseases** **Inflammatory Blistering Disorders** - Blistering disorders are classified on the level of the epidermal separation - These disorders are often caused by autoantibodies specific for epithelial pr basement membrane proteins that lead to unmooring of keratinocytes (acantholysis) - ***IgG*** autoantibodies to various intercellular desmogleins, resulting in bullae that are either subcorneal (pemphigus foliaceus) or suprabasilar (pemphigus vulgaris) - Pemphigus vulgaris, by far the most common type (accounting for more than 80% of cases worldwide), involves the mucosa and skin, especially on the scalp, face, axilla, groin, trunk, and points of pressure. It may present as oral ulcers that may persist for months before skin involvement appears. Primary lesions are superficial vesicles and bullae that rupture easily, leaving shallow erosions covered with dried serum and crust - ***IgG*** autoantibodies to basement membrane proteins and produces a subepidermal blister - ***IgA*** autoantibodies to fibrils that bind the epidermal basement membrane to the dermis and also produces subepidermal blisters Noninflammatory blistering disorders include inherited defects in proteins that stabilize the epidermis (e.g., epidermolysis bullosa), as well as defects in porphyrin synthesis (the porphyrias) that lead to sun-induced skin damage through uncertain mechanisms. **Disorders of Epidermal Appendages** Acne Vulgaris - Middle to late teenage years, acne vulgaris affects males and females, with males tending to have more severe disease - Acne is seen in all races but is usually milder in people of Asian descent - May be induced or exacerbated by: - Drugs: corticosteroid, adrenocorticotropic hormone, testosterone, gonadotropins, contraceptives, trimethadione, iodides, and bromides - Occupational exposures: cutting oils, chlorinated hydrocarbons, and coal tars - Conditions that favor occlusion of sebaceous glands, such as heavy clothing, cosmetics, and tropical climates - Hormonal changes! - ***Open comedones*** are small follicular papules containing a central black keratin plug. This color is the result of oxidation of melanin pigment (not dirt). - BLACK HEAD - ***Closed comedones*** are follicular papules without a visible central plug. Because the keratin plug is trapped beneath the epidermal surface, these lesions are potential sources of follicle rupture and inflammation. - WHITE HEAD - Pathogenesis of acne is incompletely understood and is likely multifactorial - 1\. Keratinization of the lower portion of the follicular infundibulum and development of a keratin plug that blocks outflow of sebum to the skin surface - 2\. Hypertrophy of sebaceous glands during puberty under the influence of androgens - 3\. Lipase-synthesizing bacteria (*Propionibacterium acnes)* colonizing the upper and mid portion of the hair follicle, converting lipids within sebum to proinflammatory fatty acids - 4\. Secondary inflammation of the involved follicle Rosacea - Common disease of middle age and beyond - Four stage are recognized: - 1\. Flushing episodes (pre-rosacea) - 2\. Persistent erythema and telangiectasia - 3\. Pustules and papules - 4\. Rhinophyma (permanent thickening of the nasal skin by confluent erythematous papules and prominent follicles) - High cutaneous levels of the antimicrobial *peptide cathelicidin*, an important mediate of the cutaneous innate immune response - Rosacea is characterized by a nonspecific perifollicular infiltrate composed of lymphocytes surrounded by dermal edema and telangiectasia - In the pustular phase, neutrophils may colonize the follicles, and follicle rupture may occur and cause a granulomatous dermal response - The development of rhinophyma is associated with hypertrophy of sebaceous glands and follicular plugging by keratotic debris - - - - Erythema Nodosum - Presents poorly defined, exquisitely tender, erythematous plaques and nodules that may be more readily palpated than seen - Often associated with infections (β-hemolytic streptococcal infection, tuberculosis, and less common, coccidioidomycosis, histoplasmosis, and leprosy), drug administration (sulfonamides and oral contraceptives), sarcoidosis, inflammatory bowel disease, and certain malignant neoplasms - Fever and malaise may be present - Pathogenesis is a mystery - Thought to be caused by a delayed hypersensitivity reaction to microbial or drug-related antigens - Over the course of weeks, lesions usually flatten and become bruise-life, leaving no residual clinical scars, while new lesions develop **Infection** Verrucae (warts) - Verrucae are squamoproliferative lesions caused by human papillomaviruses (HPVs) - General self-limited, regressing spontaneously within 6 months - 2 years - This is cause an exaggeration of normal skin composition with the stratum corneum being irregularly thickened - Transmission is through direct skin contact although contact with viral particles on inanimate objects has been known to cause infection - Genital infection is usually acquired through sexual contact; anogenital warts are caused predominantly by HPV types 6 and 11 - Appearance varies depending on the location and virus. (named by location) - Verruca vulgaris is the most common type of wart. The lesions of verruca vulgaris may occur anywhere but are most often found on the hands, particularly on the dorsal surfaces and periungual areas, where they appear as gray-white to tan, flat to convex, 0.1- to 1-cm papules with a rough, pebble-like surface (Fig. 25.38A). **Verruca plana, or flat wart**, is common on the face or the dorsal surfaces of the hands. The warts are slightly elevated, flat, smooth, tan papules that are generally smaller than verruca vulgaris. **Verruca plantaris and verruca palmaris** occur on the soles and palms, respectively. These rough, scaly lesions may reach 1 to 2 cm in diameter, may sometimes coalesce, and may be confused with ordinary calluses. **Condyloma acuminatum** (venereal wart) occurs on the penis, female genitalia, urethra, perianal areas, and rectum. Venereal warts appear as soft, tan, cauliflower-like masses that occasionally reach many centimeters in diameter. Molluscrum Contagiosum - common , self-limited viral disease of the skin caused by a poxvirus - Infection spread by direct contact, particularly amount children and young adults - Multiple lesions may occur on the skin and mucous membranes, with a predilection for the trunk and anogenital area - Individual lesions are firm, often pruritic, pink to skin-colored umbilicated papules - A curd-like material can be expressed from the central umbilication Impetigo - Common superficial bacterial infection of skin - Highly contagious and is frequently seen in otherwise healthy children as well as occasionally in adults in poor health - 2 forms exist: *Impetigo contagiosa and Impetigo bullosa* - Differ from each other simply by the size of the pustules - Both most commonly caused by S. aureus - Patho: bacteria in the epidermis evoke an innate immune response that causes epidermal injury, leading to local serous exudate and formation of a scale crust (scab) - Related to bacterial production of a toxin that specifically cleaves desmoglein 1, the protein responsible for cell-to-cell adhesion within the uppermost epidermal layers - Clinical manifestations: formation of vesicles, pustules, and yellow/honey-colored crusts - Innate immune response Superficial Fungal Infections - *Trichophyton Rubrum* causes tinea - Infection (tinea) named after location: - Tinea **cap**itis (scalp) - usually occurs in children and is only rarely seen in infants and adults. - dermatophytosis of the scalp characterized by - asymptomatic, patchy skin lesions associated with mild erythema, crust formation, scaling, and frequent hair loss. - Tinea **fac**iei (face) - Tinea corporis (trunk) - Common superficial fungal infection of skin that affects persons of all ages, but particularly children. - Predisposing factors include excessive heat and humidity - Exposure to *infected animals*, and chronic dermatophytosis of the feet or nails. - Most common type of tinea corporis is an expanding, round, slightly erythematous plaque with an elevated scaling border - Tinea **man**us (hand) - *Tinea cruris (groin)* - *Occurs most frequently in the inguinal areas of obese men during warm weather* - *Heat, friction, and maceration all predispose to its development.* - *Infection usually first appears on the upper inner thighs as moist, red patches with raised scaly borders.* - Tinea **ped**is (athete's foot) - Affects 30% to 40% of the population at some time in their lives - Diffuse erythema and scaling, often initially localized to the web spaces. - Most of the inflammatory reaction, however, appears to be the result of bacterial superinfection and is not directly related to the primary dermatophytosis. - Spread to (or primary infection of the nails) is referred to as *onychomycosis.* This produces discoloration, thickening, and deformity of the nail plate. - Onychomycosis (nails) - Tinea barbae (beard) - is a dermatophyte infection of the beard area that affects adult men - it is relatively uncommon. - Tinea vesicolor - Usually occurs on the upper trunk and is highly distinctive in appearance - Caused by *Malassezia furfur* (a yeast, not a dermatophyte) - The lesions consist of groups of macules of varied size and color with a fine peripheral scale. - Pathophysiology: dermatophytes invade, infect, and persist in the stratum corneum. Rarely penetrate below the surface of the epidermis - Clinical manifestations: clinical signs vary depending on the location of the infection; may manifest as erythematous or plaques with peripheral scaling and central clearing - HSV-1 and HSV-2 differ serologically but are closely related genetically and cause a similar set of primary and recurrent infections - Both viruses replicate in the skin and the mucous membranes at the site of entry of the virus (usually oropharynx or genitals), where they produce infectious virions and cause vesicular lesions of the epidermis. - The viruses spread to sensory neurons that innervate these primary sites of viral replication and release. - Viral nucleocapsids are transported along axons to the neuronal cell bodies, where the viruses establish latent infection. - Reactivation of HSV-1 and HSV-2 may occur repeatedly with or without symptoms, and results in the spread of virus from the neurons to the skin or to mucous membranes. - HSV-2 infection increases the risk of HIV transmission fourfold and increases the risk of HIV acquisition twofold to threefold. HSV 1 & 2 - Lesions ranging from self-limited cold sores and gingivostomatitis to life-threatening disseminated visceral infections and encephalitis. - Fever blisters or cold **sores** favor the facial skin around mucosal orifices (lips, nose), where their distribution is frequently bilateral and independent of skin dermatomes. - Intraepithelial vesicles (blisters), which are formed by intracellular edema and ballooning degeneration of epidermal cells, frequently burst and crust over, but some may result in superficial ulcerations. - Gingivostomatitis, which is usually encountered in children, is caused primarily by HSV-1. - Vesicular eruption extending from the tongue to the retropharynx and causing cervical lymphadenopathy.Genital Herpes - Two forms of corneal lesions are caused by HSV: Herpes epithelial keratitis and herpes stromal keratitis - All herpes can be spread (shed virus) without vesicles present - Genital herpes is more often caused by HSV-2 than by HSV-1. It is characterized by vesicles on the genital mucous membranes as well as on the external genitalia that are rapidly converted into superficial ulcerations that are rimmed by an inflammatory infiltrate (Chapter 22). Herpesvirus (usually HSV-2) can be transmitted to neonates during passage through the birth canal of infected mothers. Although HSV-2 infection in the neonate may be mild, more commonly it is fulminating with generalized lymphadenopathy, splenomegaly, and necrotic foci throughout the lungs, liver, adrenals, and CNS. - HHV-6 and HHV-7 causes exanthem subitum (sixth disease), a benign rash of infants, - Has been associated with encephalitis, pneumonitis, hepatitis, and myelitis on reactivation. - Generally affects children younger than 4 years. - Maculopapular rash covering the trunk and spreading to appendages. - Symptoms: Rapid rise in temp up to 105F and cold like symptoms. - Symptoms usually subside in 3-5 days **Varicella-Zoster Virus (VZV) infections** - Acute infection with VZV causes chickenpox, and reactivation of latent VZV causes shingles (also called herpes zoster). - Mild in children but more severe in adults and in immunocompromised people. - VZV evades immune responses and establishes a latent infection in sensory ganglia. In contrast to HSV, VZV is transmitted in epidemic fashion by respiratory aerosols, disseminates hematogenously, and causes widespread vesicular skin lesions. - Latent VZV infection is seen in neurons and/or satellite cells around neurons in the dorsal root ganglia. Reactivation and clinical recurrences causing shingles are uncommon but may occur many years after the primary infection. - Localized recurrence of VZV is most frequent and painful in dermatomes innervated by the trigeminal ganglia, where the virus is most likely to be latent. - Physical manifestations: - Chickenpox rash occurs approximately 2 weeks after respiratory infection. - Lesions appear in multiple waves centrifugally from the torso to the head and extremities. Each lesion progresses rapidly from a macule to a vesicle, which resembles a dewdrop on a rose petal. - After a few days, most chicken pox vesicles rupture, crust over, and heal by regeneration, leaving no scars. - Bacterial superinfection of vesicles that are ruptured by trauma may lead to destruction of the basal epidermal layer and residual scarring. - Shingles: causes vesicular lesions, are often associated with intense itching, burning, or sharp pain because of concomitant radiculoneuritis. - This pain is especially severe when the trigeminal nerves are involved; rarely, the geniculate nucleus is involved, causing facial paralysis (Ramsay Hunt syndrome). - Due to infections in doral roots lesions follow dermatomes and present unilaterally. - If it is seen in the eye = MEDICAL EMERGENCY **Lyme Disease** - **Patho:** Tick bite that carries spirochete *Borrelia burgdorferi* from deer and mice - Much of the pathology associated with the infection is thought to be secondary to the immune response against the bacteria and the inflammation that accompanies it. - ***Clinical Manifestations:*** - Affects skin, nervous, heart, and musculoskeletal system. - Stage I: single or multiple erythematous papules that itch, burn, or sting; flulike symptoms (Bull\'s eye rash) - Stage II: meningitis, cranial nerve palsies, and peripheral neuropathy; stage III: oligoarticular arthritis - **Patho:** - *Sarcoptes scabiei* is a mite - Begins with eggs laid in the stratum corneum, hatch into larvae within 3-4 days - Contracted after close contact with an infested individual - **Clinical Manifestations:** - Small erythematous papules with overlying dry scale or crust; linear burrows - Severe, constant itching **Tick Borne Illness** Rocky Mountain Spotted Fever - **Patho:** Caused by tick that carries *Rickettsia rickettsii*; most states have reported cases. The rickettsiae then enter the bloodstream and multiply in body tissues. - **Clinical Manifestations:** Initial bite appears as papule or macule with or without a central punctate area - Within 4 to 8 days HA, fever, N/V, and muscle aches appear; macular, maculopapular rash on wrist/ankle - Ehrlichiosis and anaplasmosis have similar presentations. The rash is nonspecific and can be macular, maculopapular, or petechial. **Vitiligo (Leukoderma)** - **Patho:** Pigment disappears from a patch of skin; sudden onset - Exact cause is unknown. - Pathogenic theories include autoimmune involvement, viral causes, decreased melanocyte survival, genetic defects in the structure of the melanocyte, and neurochemical destruction of the melanocyte. **Clinical Manifestations:** - Depigmented patch with definite smooth borders **Albinism (Oculocutaneous Albinism)** - Patho: Partial or total absence of melanin arises as an inborn error in metabolism - autosomal recessive - Clinical Manifestations: - Generalized lack of skin and hair pigmentation - Eyes may show nystagmus and lack of pigmentation of the fundi - Sunscreens, sunglasses, and protective clothing used to prevent ultraviolet-induced damage