Systemic Path - Exam 3 Flashcards
What type of glands make up the endocrine system?
Ductless glands
Where are hormones from the endocrine system secreted?
Bloodstream
This organ has both exocrine and endocrine function.
Pancreas
What are mixed function organs?
Has both exocrine and endocrine function.
What are diffuse endocrine systems?
Comprised of scattered cells within organs acting locally on adjacent cells without entry into blood stream.
Which type hormones are biologically active?
Free hormones
Purpose of hormones bound to plasma proteins
Serve as a reserve for acute changes (e.g. thyroid and steroid)
General characteristics of hormones.
- Have a specific rate and pattern of secretion.
- Feedback systems: to maintain an optimal internal environment
- Affect only cells with appropriate receptors
- Excreted by one organ and deactivated by another (e.g. excreted by the kidney, deactivated by the liver or other mechanisms)
Functions of endocrine system.
- Response to stress and injury
- Growth and development
- Reproduction
- Homeostasis
- Energy metabolism
How does the feedback loop mechanism work?
- When biological sensor detects that a hormone level is low, it will cause processes that increase the hormone level.
- When the hormone level is too high, the sensors will cause a decreased in hormonal production.
Analogous to a thermostat and furnace.
Classification of diseases.
- Hyperfunction - overproduction of secretion
- Hypofunction - underproduction
- Mass effects (tumors)
The parathyroid is a derivative of…
Third and forth branchial pouches
How many parathyroid glands does the typical person have?
Most have four glands, but may vary 1-12.
Ectopic locations of the parathyroid
- intrathyroid
- intrathymic
- anterior mediastinum
Location of the parathyroid.
Normally on the posterior thyroid surface.
What cells make up the parathyroid?
- Chief cells
- Oxyphil cells
- Stromal fat
What do chief cells secrete?
parathyroid hormone (PTH)
What controls the activity of the parathyroid gland?
Free (ionized) calcium, not trophic hormones
Where does PTH act?
Bones, kidneys, and intestines
Describe PTH and regulation of systemic calcium homeostasis
- PTH increases bone resorption in bone –> increases plasma Ca++
- PTH decreases PO4 reabsorption, but increases Ca++ reabsorption in the kidney –> increases plasma Ca++
- After hydroxylation in the liver and kidney, active form of vitamin D3 (1,25-dihydroxy-vitamin D3) increases calcium reabsorption in the intestine –> increases plasma Ca++
As plasma calcium increases, this is sensed by the parathyroid glands as negative feedback –> less PTH will be produced, and this is how calcium homeostasis is maintained
What is normal PTH level?
10 to 65 nanomoles/L
What are the causes of hypercalcemia?
1) Due to raised PTH –> hyperparathyroidism (increased production of PTH)
2) Due to decreased PTH: • Hypercalcemia of malignancy • Vitamin D toxicity • Immobilization • Thiazide diuretics • Granulomatous disease (sarcoidosis)
What is hyperparathyroidism?
- Increased production of parathyroid hormone
* Serum calcium may be decreased, increased or normal, depending upon renal function
What is primary hyperparathyroidism?
Excess of parathyroid hormone from adenoma (85 to 95%), hyperplasia (5 to 10%) or carcinoma (1%)
Note: >95% of cases, primary hyperparathyroidism is caused by a sporadic adenoma or sporadic hyperplasia
Scribe note: PTH normal or increased, calcium increased
What is secondary hyperparathyroidism?
Adaptive increase in parathyroid hormone secondary to hypocalcemia and hyperphosphatemia of chronic renal failure
Scribe note: PTH increased, calcium normal or decreased
What is tertiary hyperparathyroidism?
autonomous parathyroid hyperfunction in patients with secondary hyperparathyroidism
Scribe note: Both PTH and calcium are increased since it is autonomous
Signs and symptoms of hyperparathyroidism
- Asymptomatic
* “Bones, stones, abdominal groans, psychic moans”
Effects/symptoms of the main cause of hyperparathyroidism, parathyroid adenoma:
BONE. Excess PTH acts on bone, causing calcium to leech out and cause osteoporosis (prone to fractures) and osteitis fibrosa cystica (radiolucent areas, called brown tumor, due to hemorrhage).
RENAL. Patient may develop kidney stones, frequent urination, and nephrocalcinosis (increased calcium reabsorption in renal tubules causes calcifications).
GI TRACT. Patient may develop peptic ulcer, gallstones, and acute pancreatitis
BRAIN. Hyperparathyroidism can cause depression or seizures
BLOOD. Hypercalcemia, hypophosphatemia
Brown tumor
Osteitis fibrosa cystica
What’s parathyroid adenoma?
- Benign neoplasm
- Involve a single gland, rarely two or more (<1%)
- Major cause of primary hyperparathyroidism
- Any age, F:M 3:1
- Excellent prognosis after excision
Major cause of hyperparathyroidism
Parathyroid adenoma
Appearance of parathyroid adenoma
- Sharply demarcated from the adjacent rim of normal parathyroid
- Predominantly chief cells in sheets or tubules
- Adipose tissue inconspicuous
What’s parathyroid hyperplasia?
- Classically all four parathyroid involved (frequently asymmetrical)
- Sporadic or as a component of MEN syndrome
- 75% of patients – sporadic
- 15% of patients – part of MEN 2A (not MEN 2B)
- 15% of hyperparathyroidism cases
Note: diagnosis of adenoma versus hyperplasia may depend on the size of the other glands
Appearance of parathyroid hyperplasia
- Enlarged parathyroids
- Stromal fat inconspicuous
- Usually chief cell hyperplasia, diffuse or nodular
- Variable oncocytes
- Cystic change in markedly enlarged glands
What’s parathyroid carcinoma?
- Palpable neck mass (75%)
- Excessive PTH secretion, high serum calcium > 14 mg/dl
- Non-functioning tumors are rare
- Diagnosis based on local invasion and metastases (clinical criteria, NOT microscopic criteria)
- 1/3 recur locally, 1/3 have distant metastases
Appearance of parathyroid carcinoma
- Capsular invasion
- Densely adherent to surrounding soft tissue
- Thick fibrous bands
- Predominantly chief cells arranged in solid or trabecular pattern
- Macronucleoli, more than five mitoses per 50 high-power fields, and necrosis associated with aggressive behavior
- Cytological detail, unreliable for the diagnosis of carcinoma
- Vascular invasion and metastasis (ABSOLUTE CRITERIA)
- Local recurrence (1/3 of cases), distant metastasis (in another 1/3)
What is hypoparathyroidism?
- Disorder in which insufficient parathyroid hormone (PTH) is secreted from the parathyroid glands, resulting in abnormally low levels of calcium in the blood
- Far less common
Causes of hypoparathyroidism
- Damage to the gland or its vessels during thyroid surgery
* Idiopathic, autoimmune disease, congenital
Clinical features of hypoparathyroidism
- Tetany
- Convulsion
- Neuromuscular irritability
- Cardiac arrhythmias
- Increased intracranial pressure
- Seizures
MEN stands for?
Multiple Endocrine Neoplasia
What’s MEN I?
- AKA Wermer syndrome
* Neoplasia of: pituitary, parathyroids, pancreas and carcinoids, parathyroid hyperplasia
What’s MEN IIA?
- AKA Sipple’s Syndrome
* Medullary throid carcinoma (c-cell), parathyroid hyperplasia, pheochromocytomas (tumor of adrenal medullary)
What’s MEN IIB?
- Neuromas of the eye, buccal mucosa, and GI mucosa
* There may be medullary thyroid carcinoma and pheochromocytomas
What’s the largest endocrine organ?
Thyroid
What are the thyroid hormones?
• Thyroid hormones (TH):
- Thyroxine (T4) - Triiodothyronine (T3) - Calcitonin
Layers of skin
• Epidermis - top most layer, contains melanocytes (makes pigment) and Langerhans cells (immune cells)
• Dermis - located beneath the epidermis, contains dendritic cells (immune cells) and appendages
- appendages include: hair follicles, sweat glands, Pacinian corpuscles (pressure receptors).
- Red tissue you see when you skin your knee and the epidermis has been removed
• Subcutaneous fat
Where are melanocytes derived from?
- Neural crest derived cells
- Present in epidermal basal layer
- Synthesize melanin
Synthesis of melanin
- Synthesized in melanosomes
- Catalyzed by tyrosine
- Tyrosine -> DOPA –> melanin
- Dendritic processes extend between keratinocytes
- Melanin is transferred from melanocytes to neighboring keratinocytes in melanosomes
Innate immune response: what is it, physical barriers, soluble factors, cells involved?
- Immediate defense; short lived; no memory
- Physical barriers include skin and mucosal epithelia
- Soluble factors include complement, antimicrobial peptides, chemokines, and cytokines
- Cells include monocytes/macrophages, dendritic cells, natural killer cells, and neutrophils
Adaptive immune response
- Has memory; has specificity; long lasting
- Initiated by dendritic antigen-presenting cells
- Langerhan cells in the epidermis
- Dermal dendritic cells in the dermis
- Executed by T cells and antibodies produced by B cells and plasma cells
Which dendritic antigen presenting cell is present in the epidermis?
Langerhans cells
Which dendritic antigen presenting cell is present in the dermis?
Dendritic cells
What are keratinocytes?
- Present in melanosomes
* Secrete cytokines, chemokines, arachidonic acid metabolites, complement components, and antimicrobial peptides
What are Langerhans cells?
- Antigen presenting cells in the epidermis
- Phagocytose antigens
- Migrate via lymphatics to regional lymph nodes
- Expresses protein on its surface to T lymphocytes then undergo clonal proliferation
What do Langerhans cells do, and how do they travel?
- Phagocytose antigens
- Migrate via lymphatics to regional lymph nodes
- Express antigen protein on their surface and present to T lymphocytes, then undergo clonal proliferation
Plays a similar role to Langerhans cells in the dermis…
Dermal dendritiic cells
What are natural killer (NK) cells?
- Survey the body looking for transformed or infected cells
* Kill cells directly or indirectly via the secretion of cytokines
What are macrophages?
- Cutaneous immune surveillance in the dermis
* Phagocytic function (also neutrophils): take up pathogens, recognize them, and destroy them
What is a macule?
- Circumscribed FLAT lesion
* 5mm or smaller in diameter
What is a patch?
- Flat circumscibed lesion
* > 5mm
What is a papule?
- ELEVATED dome-shaped or flat-topped lesion
* 5mm or less across
What is a nodule?
Greater than 5mm
What is a pustule?
Discrete, pus-filled, raised lesion
What is a plaque?
- Elevated flat-topped lesion
* Greater than 5mm across
What is a petechiae?
- Small (1-2mm) red or purple macules due to minor hemorrahage
- Do not blanch with pressure
What is a purpura?
- Large hemorrhagic lesion
- 0.3 - 1cm red or purple macules and patches
- Do not blanch with pressure
These two skin lesions do not blanch with pressure…
Purpura and petechiae
What is a vesicle?
- Fluid-filled raised lesion
* 5mm or less across
What is a bulla?
- Fluid-filled raised lesion
* Greater than 5mm
What is a wheal?
- Itchy, transient, elevated lesion, +/- erythema
* Dermal edema
What is a scale?
- Dry, horny, plate like excrescence
* Imperfect cornification
What is lichenification?
• Caused by repeated rubbing/scratching
• Thickened and rough skin, prominent skin markings
** Looks like lichen
What is ulceration?
Complete loss of the epidermis, revealing dermis or subcutis.
What is eschar?
When tissue dies, turns black, and sloughs.
What is onycholysis?
Nail separates from nail bed.
Microscopic terms used to describe skin findings
- Hyperkeratosis: thickening of the stratum corneum
- Basket weave hyperkeratosis: most normal healthy skin on our body is keratinized in this fashion
- Compact hyperkeratosis: the soles of feet and palms of hands are thicker
- Parakeratosis: keratinization with retained nuclei in the stratum corneum
- Hypergranulosis: hyperplasia of the stratum granulosum
- Spongiosis: intercellular edema of the epidermis
- Hydropic swelling (ballooning): intracellular edema of keratinocytes
- Acanthosis: diffuse epidermal hyperplasia wih thickening of the malphigian layer
- Acantholysis: loss of intercellular cohesion between keratinocytes
- Dysplasia: premalignant proliferation; disorderly, pleomorphic, lacks maturation
- Dyskeratosis: premature keratinization of cells below the stratum granulosum
What is hyperkeratosis?
Thickening of the stratum corneum.
• Basket weave hyperkeratosis: most normal healthy skin on our body is keratinized in this fashion
• Compact hyperkeratosis: the soles of feet and palms of hands are thicker
What is parakeratosis?
Keratinization with retained nuclei in the stratum corneum.
What is hypergranulosis?
Hyperplasia of the stratum granulosum.
What is spongiosis?
Intercellular edema of the epidermis.
What is hydropic swelling (ballooning)?
Intracellular edema of keratinocytes.
What is acanthosis?
Diffuse epidermal hyperplasia with thickening of the malphigian layer.
What is acantholysis?
Loss on intercellular cohesion between keratinocytes
What is dysplasia?
- Premalignant proliferation
* Disorderly, pleomorphic, lacks maturation
What is dyskeratosis?
• Premature keratinization of cells below the stratum granulosum.
Histologic pattern of inflammatory skin disease –> perivascular dermatitis
Can be superficial and deep
Histologic pattern of inflammatory skin disease –> vasculitis
- Injury to blood vessels, causing blood cells to leak out
* Grossly we see petechiae and purpura
Histologic pattern of inflammatory skin disease –> vesicular dermatitis
Blistering diseases like pemphigoid
Histologic pattern of inflammatory skin disease –> diffuse dermatitis
Example: sarcoidosis
Histologic pattern of inflammatory skin disease –> panniculitis
Subcutaneous fat is inflamed.
Group of disorders of differing etiologies that share similar morphologic and histological features spongiotic dermatitis.
Skin rash
Eczematous dermatitis
Acute appearance of eczematous dermatitis
- Erythema
- Aggregates of tiny pruritic vesicles (1mm)
- Itchy, excude clear fluid, and become encrusted
Chronic appearance of eczematous dermatitis
- Scaly and thickened (lichenification) from continued scratching
- Acanthosis: spongiosum layer gets thickened due to causes like rubbing or psoriasis
- Hyperkeratosis: thickening of the stratum corneum
- Dermal scarring
A generic term applied to acute or chronic inflammatory reactions to substances that come in contact with the skin.
Contact dermatitis
Two variants of contact dermatitis
- Allergic contact
* Irritant contact
What is allergic contact dermatitis?
- Idiosyncratic immunological reaction to an environmental allergen
- Cell-mediated, delayed (type IV) hypersensitivity reaction mediated by Langerhans cells and t-cells.
- Ex: poison ivy; nickel; chromates; synthetic rubber; primula; topical creams
What is irritant contact dermatitis?
- Follows exposure to physical or chemical substances capable of direct damage to the skin.
- Mechanisms include keratin denaturation, removal of surface lipids and water, damage to cell membranes, and direct cytotoxic effects
- Ex: Soaps, detergents, acids and alkalis, industrial solvents
What is atopic dermatitis?
- Chronic, relapsing eczematous rash.
- Any age, but often begins in infancy
- In infants it often affects: head, face, neck, diaper area, and extensor aspects
- In childhood it involves flexural aspects (e.g. back and knees).
- Pruritus is intense - scratching leads to lichenification
- Risk of secondary bacterial, dermatophyte and viral infections
- Disease improves during childhood, with >50% clearing by teen years.
Etiology of atopic dermatitis
Multifactorial: • Genetic susceptibility • Abnormal skin barrier function • Abnormal immune system activity • Environmental factors
Personal or family history of asthma or allergies:
• 75% have a family history of atopy (genetic disposition to develop an allergic reaction)
• 50% have associated asthma or hay fever
Associated with dry skin (xerosis): worsens in the winter months
A very common chronic dermatosis characterized by redness and scaling where the sebaceous glands are most active: face, scalp, presternal area, body folds
Seborrheic dermatitis
- Presents in infants; second peak in adults
- Male predominance; often a family history
Skin findings of seborrheic dermatitis
Erythematous or yellowish patches, covered by a greasy scale
Pathogenesis of seborrheic dermatitis
Pathogenesis is unknown.
• Linked with the yeast Malessezia, immunologic abnormalities, sebaceous activity, stress, neurological disorders, and AIDS
Course of seborrheic dermatitis
- Self-limited with a good prognosis in infants
* Chronic and relapsing in adults
Delayed hypersensitivity type 4 reaction to photo product of topical or systemic medications and chemicals
Photoallergic reactions
• An allergic reaction to something on skin or in blood, as a result of photochemical reaction
Skin lesions observed in photoallergic reactions
- Eczematous papular, vesicular, scaling, and crusted
* Can persist for months or years
What are phototoxic reactions?
UV radiation associated with use of medications causes formation of toxic photoproducts such as free radicals
• Damages DNA or cell membranes
Skin findings of phototoxic reactions
- Occurs on sun-exposed skin
- Occurs minutes to hours after sun exposure
- Mimics severe sunburn: erythema, edema, and blistering desquamation and post inflammatory hyperpigmentation
An acute self-limited, usually mild, often relapsing mucocutaneous syndrome characterized by presence of target-shaped plaques with or without central blisters, predominantly on face and extremeties.
Erythema multiforme
• Any age, peaks in 20-40s; children
What is erythema multiforme minor?
No mucosal involvement
What is erythema multiforme major?
Mucosal involvement
Pathogenesis of erythema multiforme
Epithelial cells are killed by skin-homing CD8+ cytotoxic T lymphocytes
• Immunologic response, most often, to a recurrent herpes simplex virus
• Can also be stimulated by M. peumoniae, drugs, neoplasia
• Begins a week after a recurrence of herpes
In other words: caused by CD8+ T-cells that kill epithelial cells. This is stimulated by herpes simplex cirus, which makes us attach our own skin.
TARGET LESIONS, macules, papules, vesicles, bullae are associated with which inflammatory skin disease?
Erythema multiforme
Additional skin findings:
• symmetric, extremities, arms, legs, hands, feet, anywhere
• Half have oral or vermillion border lesions
Microscopic appearance of erythema multiforme
- interface dermatitis because vacuolar change and cleft formation occur at the dermal-epidermal junction
- Necrotic basal keratinocytes
- Lymphocytic infiltrates of interface and superficial perivascular zones.
What is Stevens-Johnson Syndrome, aka Toxic Epidermal Necrolysis?
- Acute, life-threatening skin and mucous membrane reaction characterized by extensive necrosis and detachment of the epidermis.
- Previously considered severe variants of erythema multiforme, but now considered a separate entity.
- An epidermal emergency
Stevens-Johnson-Syndrome and Toxic Epidermal Necrolysis are the same process, but vary in the % of involved surface area…
- SJS if involved area < 10% of body surface
- SJS/TEN overlap if 10-30%
- Toxic epidermal necrolysis if > 30%
Risk factors for SJS and TEN
- Rare
- Any age, but risk increases with age
- 2F:1M predilection
- Increased risk: HIV, collagen vascular disease and cancer
Mortality SJS vs TEN
SJS: 5-12%
TEN: > 30%
Skin findings on SJS/TEN
- Confluent, erythematous, purpuric and target-like macules evolve into flaccid blisters and epidermal detachment
- Mostly trunk, extremities, and mucous membranes
Pathogenesis of SJS/TEN
Cell-mediated cytotoxic reaction against keratinocytes leads to massive apoptosis.
Common (1%), pruritic (itchy), symmetrical, papulosquamous dermatosis
Lichen planus
Add’l info:
• Often presents in fourth to sixth decades; uncommon in childhood
• Slight female predominance
• Familial cases reported. Associated with specific HLA types
• Usually self-limiting-lesions clear from weeks to 1 or 2 years. Sometimes protracted.
Skin findings for lichen planus
- Four P’s: polygonal, pruritic, purple papule; few millimeters to 1 cm
- Wickham’s striae - white streaks
Inflammatory skin disease where Wickham’s striae (white streaks) are observed
Lichen Planus
Sites affected by Lichen Planus
- Flexor aspect of the wrists, the forearms, the extensor aspect of the hands and ankles, lumbar area, nails, glans penis and generalized
- Oral involvement common: may involve pharynx, larynx, esophagus, nose, anus, and genitalia; ocular rare
Microscopic appearance of Lichen Planus
- Interface dermatitis
- Dense, band like lymphocytic infiltrate along the D-E junction
- Vacuolar degeneration of the basal layer
- Hypergranulosis, hyperkeratosis and sawtoothing of epidermis
- Necrotic keratinocytes - “Civatte bodies”
Civatte bodies, which are necrotic keratinocytes, are observed in which inflammatory skin disease?
Lichen Planus
Pathogenesis of Lichen Planus
- Possibly expression of altered external antigen stimulus elicits a cell-mediated cytotoxic T-cell immune response at the level of the dermoepidermal junction
- Assoociated with viral infections, metals, and drugs.
- Body mistakes own antigens for external antigens
Course of Lichen planus
- Unpredictable disease
- Typically persists for 1-2 years, but may follow a chronic, relapsing course over many years
- Rx: Topical and systemic glucocorticoids, cyclosporine
- NAILS may be affected: longitudinal ridging, thinning, and distal splitting of the nail plate
Common chronic inflammatory dermatosis characterized by erythmatous scaly plaques of the elbows, knees, scalp, lumbosacral areas and other sites
Psoriasis
Which inflammatory skin disease is this:
- Associated with arthritis, myopathy, enteropathy, joint disease, AIDS.
- Polygenic trait
Psoriasis
Additional info:
• Any age, bimodal
• Often presents in the teens and in early adult life (type I).
• Second peak in sixth decade (type II).
More on polygenic trait: one parent has psoriasis 8% of kids get psoriasis. Both parents have psoriasis, 41% of kids get psoriasis.
Acute form of psoriasis
Eruptive, guttate psoriasis; multiple small lesions; greater tendency toward spontaneous resolution; 2%
Chronic stable plaque psoriasis
- Majority of patients
* Chronic indolent lesions present for months and years
Pathogenesis of psoriasis
- Multifactorial, both genetic and environmental factors
- Interactions between CD4+ T-cells, CD8+ T-cells, dendritic cells, and keratinocytes causing bassal keratinocytes to hyperproliferate
- Strong association with HLA-Cw6; only 10% develop psoriasis
- Systemic glucocorticoids, oral lithium, antimalarial drugs, interferon, adrenergic blockers and alcohol can cause flares
Which inflammatory skin disease has a strong association with HLA-Cw6?
Psoriasis
Skin findings for psoriasis
- Begin as papules, coalesce to form raised, sharply demarcated plaques, silvery scale surface, erythematous base
- Elbows, knees, scalp, lumbosacral areas, intergluteal cleft, and glans penis
- Nail pitting and onycholysis
- Auspitz’s sign: small droplets of blood when removing scales
What is Auspitz’s sign, and in which inflammatory skin disease is it observed?
- Auspitz’s sign is small droplets of blood when removing scales
- Psoriasis
Destruction of the interphalangeal joints resulting in telescoping fingers.
Psoriatic arthritis
Microscopic appearance of psoriasis
- Acanthosis
- Elongation of the rete ridges, suprapapillary thinning, parakeratotic scale, spongiosis and superficial perivascular inflammation
- Munro’s microabscesses - neutrophils aggregates within the parakeratotic stratum corneum
- Spongiform pustules - neutrophils form small aggregates within epidermis
In which inflammatory skin disease are Munro’s microabscesses and spongiform pustules are observed?
Psoriasis
- Munro’s microabscesses: neutrophils aggregates within the parakeratotic stratum corneum
- Spongiform pustules: neutrophils form small aggregates within epidermis
Inflammatory skin diseases include _______ disorders and _______
Blistering disorders; adverse cutaneous drug reactions
Infectious skin diseases can be _____, _____, or _____
Viral, fungal, or infestations
Pemphigus Vulgaris, Bullous Phemphigoid, Dermatitis Herpetiformis
Blistering Disorders
Exanthematous drug eruption, Acute exanthematous pustulosis, Acneiform eruptions, Urticarial eruptions, Fixed drug eruption
Adverse cutaneous drug reactions
Verruca vulgaris, Mulluscum contagiosum, Herpes simplex, Varicella zoster (chickenpox and shingles)
Viral diseases
Dermatophyte infections, pityriasis versicolor, candida infection
Fungal disease
Pediculosis
Infestations
What is pemphigus?
- A serious autoimmune mucocutaeous blistering disorder caused by IgG autoantibodies against desmogleins (proteins involved in cell to cell attachment) causing acantholysis and intraepidermal bullae.
- Disease associated with specific HLA haplotypes.
- Majority fourth to sixth decades; M = F
Net-like pericellular IgG deposit for immunofluorescence indicates this…
Pemphigus
Skin findings for pemphigus vulgaris..
- Superficial vesicles and FLACCID bullae which rupture leaving shallow crusted erosions.
- Commonly involves scalp, face, axilla, groin, trunk, and pressure points.
- Oral ulcers may persist for months before onset of skin involvement.
- Extracutaneous sites include the nasopharynx, larynx, esophagus, ear, eye, urethra, anal, and colonic mucosa.
- Nikolsky sign positive, dislodge epidermis by lateral pressure near lesions.
Which blistering disorder involves positive Nikolsky sign and dislodge epidermis by lateral pressure near lesions?
Pemphigus vulgaris
Treatment for Pemphigus vulgaris
• Systemic corticosteroids, immunosuppressive agents. Manage fluids and infections
Course of Pemphigus vulgaris
- Systemic glucocorticoids and use of immunosuppressive therapy have dramatically improved the prognosis; still significant mortality because patients have trouble maintaining fluid dynamics (ooze causes loss of water) and high risk of infection.
- Before glucocorticoid therapy, almost invariably fatal.
Microscopic appearance of pemphigus vularis
- Acantholysis: the lysis, of the desmosomes connecting squamous cells leads to a suprabasal vesicle.
- Superficial dermal infiltration by lymphocytes, histiocytes, and eosinophils.
What is bullous pemphigoid?
- A bullous autoimmune disease usually in elderly patients.
* Most cases sporadic. Few associated with UV light and medications.
Pathogenesis of bullous pemphigoid
- Auto-antibodies react with basal cell – basement membrane hemidesmosomes involved in dermoepidermal bonding.
- Two forms of antigen recognized: BPAG1 and BPAG2 (collagen type XVIII).
- Causes complement activation, recruitment of neutrophils & eosinophils and injury.
What antigens are recognized in Bullous Pemphigoid?
BPAG1 and BPAG2 (collagen type XVIII).
Skin findings of Bullous Pemphigoid
- TENSE bullae, filled with clear fluid, on normal or erythematous skin usually up to 2 cm or greater in diameter
- Nikolsky sign negative
- Affects any area; lower abdomen, thighs, forearms, axillae, and groin most common
- Oral lesions in 10% to 15%; usually appear after skin lesions
Treatment for bullae pemphigoid
Systemic prednisone alone or combined with azathioprine
Course of bullae pemphigoid
- Patients often go into a permanent remission after therapy.
- Some go into spontaneous remission without therapy.
Microscopic appearance of bullous pemphigoid
- SUBEPIDERMAL BLISTERS containing eosinophils, lymphocytes, and occasional neutrophils.
- Dermal edema, perivascular lymphocytes and eosinophils.
When doing immunoflorescence a linear deposition of IgG and complement in the basement membrane zone…
Bullous pemphigoid
What is dermatitis herpetiformis?
- A rare, chronic, intensely burning, pruritic papulovesicular eruption associated with GLUTIN SENSITIVE ENTEROPATHY AND IgA DEPOSITS in upper dermis.
- all ages, but 20-40 years most common
- Male to female ratio is 2:1
- Caucasians mainly affected; rare in Asians and blacks
- Familial involvement; up to 10% of cases
- Relatives of patients with DH have increased risk for celiac disease.
Relatives of patients with dermatitis herpetiformis have increased risk for this…
celiac disease
Skin findings for dermatitis herpetiformis
- Pruritic papulovesicular and urticarial rash
- Often symmetrical, posterior scalp, shoulders, back, buttocks, and extensor aspects of the limbs; excoriation and/or lichenification
- Occasionally, larger blisters. Oral involvement is rare.
Pathogenesis of dermatitis herpetiformis
- Genetically predisposed patients develop IgA antibodies to gluten in diet
- Antibodies cross-react with reticulin, a component of the fibrils that anchor the epidermal basement membrane to the dermis.
- Asymptomatic patients can develop GI lesions with large gluten intake. Some people with DH and GSE respond to a gluten free diet.
- Increased incidence of thyroid disease, insulin-dependent diabetes mellitus, and connective tissue diseases.
Immunofluorescence reveals discontinuous, granular deposits of IgA localized to the tips of ermal papillae in normal appearing skin.
Dermatitis Herpetiformis
Treatment for dermatitis herpetiformis
Sulfones; gluten free diet
Microscopic findings for dermatitis herpetiformis
- Papillary dermal neutrophilic microabscesses within the tips of the dermal papillae.
- Coalesce to multilocular subepidermal vesicles.
- Dermal mixed inflammatory infiltrate of lymphocytes, histiocytes, and abundant neutrophils.
What are adverse cutaneous drug reactions?
- Mimic virtually all skin rashes.
- First consideration in the DDx (differential diagnosis?) of a suddenly appearing eruption.
- Occur in both systemic or topical administration of a drug.
- Most are mild, pruritic, and resolve after drug discontinued.
- Severe, life-threatening ACDRs do occur.
What causes adverse cutaneous drug reactions?
- Caused by immunologic and nonimmunologic mechanisms.
- The majority are immunologic hypersensitivity reactions and may be of types I, II, III, or IV.
- Nonimmunologic mechanisms include idiosyncratic, irritant toxicity photosensativity reaction, accumulation of drug, atrophy secondary to drug effect.
What is exanthematous drug eruption?
- Exanthem = breaking out in mouth
- Moribiliform = measles-like
- Hypersensitivity reaction to an ingested or parenterally administered drug
- Symmetric; almost always on trunk and extremities
- Intertriginous areas
What are pustular eruptions?
- Acute generalized exanthematous pustulosis
- Acute febrile eruption; often leukocytosis
- Drug or virus can trigger the eruption
Skin findings for pustular eruptions
- Nonfollicular sterile pustules on a diffuse, edematous erythema
- Usually starting in the folds and/or the face
- Resolves spontaneously in two weeks
Acneform eruptions (mimics acne) may appear in atypical areas, such as on the arms and legs, in this adverse cutaneous drug reaction…
Pustular eruptions
What are urticarial eruptions?
- Pruritic red WHEALS, generally last for < 24 hours; new lesions can develop
- Pruritus, cutaneous flushing, nausea, vomiting, diarrhea, abdominal pain, rhinorrhea, laryngeal edema, bronchospasm, hypotension
- Angiodema - deep dermal and subcutaneous tissues swollen, nonpruritic; lasts for 1-2 hours, up to 2-5 days
- Can be IgE-mediated or non-IgE-mediated
- IgE mediated: immediate hypersensitivity reaction: penicillin; ABs
- Non IgE mediated: direct stimulation of mast cells: NSAIDs, ACE-inhibitors and opioids
What are fixed drug eruptions?
- Solitary, erythematous,dusky macules or plaques; May blister
- 30 min to 8-16 hours after ingestion
- ** On rechallenge, lesions recur in same spot; often with new lesions
- Commonly genitalia and perianal area; anywhere
- +/- burning fever, malaise, and abdominal symptoms
- Acute phase lasts days to weeks; residual hyperpigmentation
- Hundreds of drugs can cause fixed eruption
Which adverse cutaneous drug reaction on rechallenge, lesions recur in the same spot?
Fixed drug eruptions
What is verruca vulgaris?
- Common wart
* Human papillomavirus (HPV) infection
Common warts (verruca vulgaris) are caused by HPV types…
1, 2, 4, 7, and 26-29
Skin findings for verruca vulgaris
- Firm, flesh colored, keratotic papules 1-10mm
- Anywhere, any age
- Most common location: backs of the hands, fingers and knees
- Persist for months up to years and often regress spontaneously
Microscopic finding for verruca vulgaris
- Acanthosis
- Hyperkeratosis
- Papillomatosis
- Hypergranulosis
- Inward folding of rete
Treatment for verruca vulgaris
- Topical salicylic acid preparations, liquid nitrogen, and very light electrocautery for initial therapy.
- Burn or freeze warts off
HPV types that cause plantar warts
- Plantar surface of feet can get warts
* Caused by HPV 1, 2, 4, 63
HPV types that cause planar warts
HPV 3, 10, 27, 38, 41, 49, 75, 76
HPV types that cause condyloma accuminatum
- Fleshy moist warts on genitalia, can look like syphilis
* HPV 6, 11, 30, 43, 43, 44, 45, 51, 54, 55, 70
HPV types that cause epidermodysplasia verruciformis
- A genetic disease, patient is highly predisposed to HPV infection
- HPV 5
What is mulluscum contagiosum?
Viral skin infection from DNA pox virus
Transmission of mulluscum contagiosum
Direct cutaneous contact; fomites; sexual contact in young adults
Skin findings for mulluscum contagiosum
- Clusters of small 1 to 6 mm white, pink or brown papules with CENTRAL PIT (umbilicated)
- Can be much larger in HIV patients
- Face, trunk, and limbs
• COURSE: may persist for months or occasionally years and remit
Microscopic appearance of Mulluscum Contagiosum
- Proliferation of epidermis in PEAR shaped lobules
* Maturing epidermal cells contain mulluscum bodies, eosinophilic inclusions compressing the nucleus
Which viral skin disease is associated with pear-shaped lobules of epidermal proliferation with pink bodies (mulluscum bodies) that rise into the umbilication?
Mulluscum contagiosum
Are HSV-1 and HSV-2 DNA or RNA viruses?
DNA
HSV-1 usually causes…
• Herpes labialis
HSV-2 usually causes…
• Herpes genitalis
How is HSV transmitted?
- Transmitted through mucosal surfaces or break in skin by contact or exposure to secretions.
- First-episode often with fever and malaise
What is herpetic whitlow?
• HSV infection, involvement of a finger or hand; often healthcare workers, dental practitioners
How to diagnose this is a herpes virus?
- Tzank smear
- Unroof a vesicle and scrape the base onto a slide
- Viral cytopathy present in cells
Skin findings for herpes simplex
- Small grouped vesicles
- +/- erythematous base
- Evolve into pustules, rupture and form a crusted ulcer
- Mucosal lesions ulcerate early
Microscopic findings for herpes simplex
- Ballooning degeneration coalesce to intraepidermal vesicle
- Multinucleation
- Intranuclear inclusions
- Nuclei have a ground-glass look because millions of live virus inside
- Dense red inclusion is a degeneration byproduct
- Nuclear molding
- Margination
- Almost looks like vasculitis, because so much dermal inflammation
Course of herpes simplex
- Primary episode resolve completely in around 15 days
- Virus persists, become latent within the ganglia of the corresponding sensory nerve
- Recurrent HSV lesions are usually less florid than the first infection without general symptoms
- Secondary outbreaks are precipitated by sunlight, fever, menstruation, pregnancy, HIV infection, emotional stress, or local trauma
Treatment ofr herpes simplex
Acyclovir tropical and oral
What is varicella zoster?
- Herpes varicella zoster virus infection
- Chickenpox
- Worldwide, all races, gender and age
- Largely a childhood disease < 10 years of age
- Incubation period 2-3 weeks
- ** Remains in anterior horn cells and be reactivated as herpes zoster infection (shingles)
Mode of transmission of varicella zoster?
- Highly contagious
- Inhaled fomite droplets
- Direct contact with the fluid from the open sores
Used to diagnosis chickenpox/varicella zoster
Tzank smear
Skin findings for chickenpox
- Pruritic red papules & vesicles to crusted ulcer
- Commonly affected areas include trunk, back, face
- Spreads distally (lesions usually start centrally - near bellybutton - then grow out peripherally)
- Can involve palms soles and mouth
- Remain infectious for 4-5 days until vesicles crusted
What are varicella zoster - shingles?
• Reactivation of varicella virus infection manifests as a painful outbreak of papules and vesicle in a dermatome distribution
Shingles, increasing incidence with…
- Age: average 55 y/o
- Immunosuppression
- Malignancy, especially from lymphoproliferative disorders and chemotherapy/radiotherapy
- HIV/AIDS: eightfold increased incidence of HZ
- Most cases triggering factors are not known
What is prodrome?
Shingles may have a prodrome, meaning certain symptoms occur before specific symptoms of shingle occur: • pain in dermatome distribution • fever and headache • lymph nodes enlarged and tender • 1-3 day prior to rash
Skin findings for varicella zoster-shingles
- Crops of red papules, progress to vesicles in a dermatome pattern
- Thoracic, lumbar, facial
- Lesions very painful
Even after rash resolves you can have post-herpetic neuralgia:
• Pain may persist for months or years
Treatment for varicella zoster
- Acyclovir
* Prevention through vaccination
What is impetigo?
- Superficial staph aureus skin infection; strep pyogenes may also be the culprit
- Can occur at any age, but most common in children
How is impetigo spread?
- Contagious
* Spread by close contact through primary breaks in skin or secondary involvement of rash or preexisting lesion
Clinical presentation of impetigo
- Bullous (less common):
- caused by an epidermolytic toxin produced at the site of intefection (bacteria produces toxin that causes epidermal cells to lyse)
- causes intraepidermal cleavage below or within the stratum granulosum
- Nonbullous
Skin findings for impetigo
- Pustules and oozing patches
- Golden yellow honey crusts or blisters (bullous impetigo)
- Most often exposed areas such as the hands and face, or in skin folds (axilla)
Golden yellow honey crusts or blisters observed in …
Impetigo
Microscopic appearance of impetigo…
Neutrophil filled subcorneal vesicle
What is cellulitis?
- Bacterial infection of skin and subcutis
* Usually caused by strep pyogenes (2/3), and staph aureus (1/3)
Skin findings for cellulitis
- Expanding area of redness, swelling, warmth, tenderness, blistering abscess, ulteration
- Often fever and leukocytosis
- Can ascend up lymphatics = lymphangitis
- Infection involves lymphatics
- Red line originates from the cellulitis leading to draining lymph nodes
- Minor trauma to the skin is common cause
- Seen commonly in peripheral vascular disease, diabetes, lymphedema, and alcohol predispose
Treatment for cellulitis
Antibiotics
What is scarlet fever?
• Streptococcus pharyngitis with erythrogenic toxic strains (a streptococcus infection - a toxin causes redness in affected person)
Clinical findings of scarlet fever
- Fever
- Sore throat
- Lymphadenopathy
- Headache
- Vomiting
- Strawberry tongue
- Abdominal pain
- Aches
- Malaise
Manifestation of strawberry tongue
Scarlet fever
What are sand paper rash
- Rashes for scarlet fever
* Begins as scarlet blotches, progresses to look like sunburn with goose pimples
Treatment for scarlet fever
Systemic antibiotic
What’s dermatophyte infections?
- Superficial fungal infection of the keratin of the stratum corneum, hair or nail
- Three species: Microsporum, Trichophyton, and Epidermophyton
- Spread is by contact, animals, or soil
- Favors moist and warm conditions
Skin findings for dermatophyte infections
- Expanding, erythematous, scaly, annular lesions with central clearing (ringworm)
- Less common vesicles, bullae, pustules
Treatment for dermatophyte infections
- Topical antifungals
* Systemic for severe or refractory cases
Microscopic findings for dermatophyte infections
PAS stain will reveal fungal hyphae in the stratum corneum
KOH (potassium hydroxide) prep
- Another test that can be done for dermatophyte infections
- A scraping of the lesion placed on a slide in a drop of KOH
- Visualization of fungal hyphae is a positive test
What’s Wood’s lamp?
- A backlight, which will cause infected lesion to fluoresce
- Pertains to dermatophyte infections
- Can be used for differential diagnosis against psoriasis
Clinical name for dermatophyte infection
• Tinea
Buffet of tinea infections:
• Tinea corporis - when fungal infection involves body
• Tinea capitis - involves scalp
• Tinea pedis - aka athlete’s foot
• Onychomycosis - fungal infection of nails. Less treatable when involves nails
What is pityriasis versicolor?
- Superficial fungal infection by Malassezia furfur
- Often young adults 20-40
- F:M, 2:1
- More common in warm climate
- Children more common in tropics
Skin findings for pityriasis versicolor
- Multiple, oval, well demarcated, hypo- or hyperpigmented macular lesions
- Become confluent and extensive
- Trunk and shoulders most common
Microscopic findings for pityriasis versicolor
Yeast and short septate hyphae, spaghetti and meatballs
Spaghetti and meatballs
Pityriasis versicolor
Treatment for pityriasis versicolor
Tropical antifungals
What is a candida infection?
- Persistent/recurrent infections of the skin, nails, and oropharynx
- Fungal organisms with yeast and pseudohyphal forms
- Candida albicans most common
Predisposing factors for candida infection
- Immunosuppression
- Diabetes
- Cushings disease
- Pregnancy
- Malnutrition
- HIV
- Systemic steroid and antibiotics
- Predelection for moist, occluded skin
- Intertrigo (seen below the breast), occlusive dressings, diaper dermatitis
Skin findings for candida infection
- Erythematous, pruritic, tender, painful rash
* In neonates, curd like pseudomembrane on an erythematous base
Mucosal candiasis
- Oral thrush - white patches inside mouth
- Angular chelitis - inflammation at corners of mouth
- Vulvovaginal trush
Chronic forms of candida infection frequently associated with…
Endocrinopathies
What are scabies?
- Infestation by mite
* Sarcoptes scabiei
Skin findings for scabies
- Papules and burrows between fingers or along the sides of the fingers, soles, and sides of the feet with excoriations and eczematous dermatitis
- Also affects elbows, axillae, scrotum, penis, labia
Transmission of scabies
Close personal contact and sexually transmitted
What is pediculosis?
• An infestation of sucking lice that lay their eggs on hair shafts or in seams of clothing
Species that infest humans to cause pediculosis…
- Pediculus humanus: capitus (headlice) and humanus (bodylice)
- Pthirius pubis: public lice
Transmission of pediculosis
direct contact
Skin lesions associated with pediculosis
- Vary with immune sensitivity
- From subclinical to papules, urticaria and pruritus
- May become secondarily infected
Treatment for pediculosis
- Topical insecticides: malathion, permethrin
- Environment vacuumed, bedding, clothing
- Combs and brushes cleaned
What’s actinic lentigo?
- Benign, irregular, pigmented macular lesions that involves sun-damaged skin of the middle aged and elderly
- Fair skin Caucasians most at risk
- 0.1 to > 1.0 cm
- Not precancerous, needs no Rx
Mimics lentigo maligna
Actinic lentigo
What’s vitiligo?
- Common acquired loss of pigment due to autoimmune destruction of melanocytes by cytotoxic T-cells
- Peak incidence 10 and 30 years
- More common in dark skin
- 15-30% associated autoimmune disease
Skin presentation of vitiligo.
Hyperpigmented macules enlarge and become confluent
Microscopic presentation of vitiligo
Loss of melanocytes and melanin pigment. Perivascular lymphocytic infiltrate.
What is melanocytic nevus?
- “nevus” = “birthmark”
- Benign melanocytic neoplasm; acquired or congenital
- Acquired - present in childhood and adolescence
- Skin, nails, mucosa, conjunctiva, uveal tract
- More common in pale skinned with light colored eyes
- Caucasians average 15-40 nevi
- Related to sun exposure (intermittent intense sunlight) during the first two decades of life. People who burn.
- Rare cases develop melanoma
In what type of people are melanocytic nevus more common in?
- Pale skinned with light colored eyes
* Caucasians average 15-40 nevi
What’s a junctional nevus?
- Ovoid to round, well circumscribed; light to dark brown, macular or slightly raised, up to 0.5 cm, regular border
- Micro –> proliferaion begins in nests at the dermo-epidermal junction
What’s a compound nevus?
- Raised, often warty, often deeply pigmented; circumscribed with a regular border
- Micro –> Nevus cells, still proliferating at the D-E junction, descent into the dermis and form nests
What’s an intradermal nevus?
- Raised
- +/- pigment
- May be dome shaped nodule, papillomatous, or pedunculated
- Micro –> melanocytes are only found in nests in the dermis. Cells “mature” as they descend deeper into the dermis
Congental Nevus
Risk of malignancy (if large) and can be covered with hair
Blue nevus
- Collections of spindled dermal melanocytes
* Tyndall effect: blue light is scattered more passing through the dermis
Halo nevus
A zone of HYPOpigmentation represents immunologic regression seen microscopically as an intense lymphocytic dermal infiltrate
What’s a dysplastic nevi?
- Melanocytic nevi with dysplastic melanocytic proliferation
- Isolated solitary lesions of familial autosomal dominant syndrome
- May progress to melanoma
- Most remain clinically stable and never progress
- In 36% of melanomas we find adjacent dysplastic nevi.
Skin findings for dysplastic nevi
- Large (>6mm)
- Irregular shaped
- Ill-defined border
- Variable shades of browns, tans, and pink
- May be erythematous surround
- Not all clinically atypical nevi are dysplastic
What’s dysplastic nevus syndrome?
• Inherited autosomal dominant syndrome
• Normal at birth, develop large numbers of nevi in early childhood
• Few to > hundred
• Acquire atypical clinical features
around puberty. Predilection for trunk, face, and arms; also buttocks, genitalia, breasts, scalp.
• Histology show dysplastic features.
• Increased incidence of melanoma;
50% by age 60.
• Five dysplastic nevi – relative risk
for melanoma increases to 46%.What’s malignant melanoma?
Malignant transformation of melanocytes.
Highest incidence of malignant melanoma occurs in…
- Fair skinned caucasians - highest incidence.
- The incidence increasing.
- 1 in 50 born in the US in 2010.
- 1 in 1500 in 1935.
- Mean age 52 years; 35% < 45 years of age.
Prognosis of malignant melanoma
- Early detection of melanoma - high cure rates after excision.
- Prognosis directly related to size and depth of invasion.
Etiology and pathogenesis of malignant melanoma
- Sun exposure; Genetic predisposition.
* Germline mutations in the chromosome 9p21 tumor suppressor gene, account for 40% of hereditary melanoma cases.
Risk Factors for Development of Melanoma
- Genetic markers (CDKN2a mutation)
- Skin type I/II (light skin)
- Family history of dysplastic nevi or melanoma
- Personal history of melanoma
- Ultraviolet irradiation; childhood sunburns, intermittent burning exposures
- Number (>50) and size (>5 mm) of melanocytic nevi
- Congenital nevi
- Number of dysplastic nevi (>5)
- Dysplastic melanocytic nevus syndrome
Melanoma signs, ABCDE rule
- Asymmetry: 1/2 unlike the other
- Border: irregular, poorly defined edges
- Color: not uniform; all shades of brown, black, pink
- Diameter: greater than 6.0 mm
- Elevation & enlargement: change in size or shape
Growth phases of melanoma
Most melanomas show an initial radial growth phase followed by a subsequent vertical phase.
- Radial growth: cells are running up and down rete, with upward invasion into epidermis; cells spread out laterally
- Vertical growth phase: loose E-cadherin and express N-cadherin
What is superficial spreading melanoma?
- 70% of melanomas
- Any site, lower extremities, trunk
- Radial growth phase - Months to 2 years
Microscopic appearance of superficial spreading melanoma
- Neoplastic melanocytes proliferate along D-E junction
- Pagetoid invasion of epidermis
- Severe atypia. Inflammation
- Gas not invaded dermis, so this is called melanoma in situ
What’s Nodular melanoma?
- 15% of melanomas
- Any site, trunk, head, neck
- Arises rapido; NO RADIAL GROWTH PHASE
- Brown, black, or pink, nodule
What’s lentigo maliga melanoma?
- Occurs in older patients with heavily sundamaged skin; mean age 65
- Flat, irregular variably pigmented macule or patch
- Face, neck, dorsa of hand
- 5% of melanomas
- Radial growth phase - very long; years
What’s Acral Lentiginous melanoma?
- 5-10% of melanomas
- Asians, Africans, and African Americans most common
- 50-70% of the melanomas found in these populations
- Palms, soles, subungual (nails?)
- Radial growth phase - months to years
What is mucosal melanoma?
- Can be seen in the mouth
* Biopsy patient if present
What’s Amelanotic melanoma?
• Little to no pigment - bizarre giant cells with prominent nucleoli.
Which type of melanoma is most common?
Superficial spreading melanoma (70% of melanomas)
Which type of melanoma is most commonly observed in palms, soles, subungual (nails)?
Acral lentiginous melanoma
Which type of melanoma is most commonly observed on the face, neck, dorsa of hand?
Lentigo maligna melanoma
Which type of melanoma affects any site, but more commonly the trunk, head, neck?
Nodular melanoma
Which type of melanoma affects any site, but more commonly the lower extremities, trunk?
Superficial spreading melanoma
Compare and contrast the radial growth phases of the different types of melanoma
- Superficial spreading melanoma –> radial growth phase: months to 2 years
- Nodular melanoma –> arises rapidly, no radial growth phase
- Lentigo maligna melanoma –> radial growth phase: very long; years
- Acral lentiginous melanoma –> growth phase: months to years
What is staging?
- T Staging is based on tumor thickness and +/- ulceration.
- T1: < 1.0mm
- T2: 0.1-2.0mm
- T3: 2.01-4.0mm
- T4: >4.0mm
Treatment for melanoma
- Surgical excision with 1.0 cm. Margin
- Sentinel node biopsy in lesions > 1.0mm thickness
- Complete lymph node dissection for metastatic disease
- Chemotherapy, immunotherapy for higher stage disease
Survival rates for melanoma (general idea)
- Lymph node involvement and metastasis indicates very poor prognosis.
- Presence of any mitosis (?) means only 10% survival.
What is seborrheic keratoses?
- Most common BENIGN epithelial tumor seen in middle-aged or older
- Trunk most common, also extremities, head, and neck
Skin findings for seborrheic keratoses
- Sharply delineated
- Round or oval
- Brown-black or flesh-colored warty plaques
- Millimeters to several centimeters
Activitating mutations in which growth factor is though to drive the growth of the tumor in seborrheic keratoses?
Fibroblast growth factor receptor-3
Seborrheic keratoses occur explosively in large numbers associated with gastric adenocarcinoma…
Leser-Trelat sign
Microscopic appearance of seborrheic keratoses
- Exophytic and sharply demarcated proliferation of small basal like keratinocytes
- Hyperkeratotic with horn cysts
What is dermatoheliosis?
- Means chronic photodamage
- Involves epidermis, vascular system, and dermal connective tissue
- Severity depends on duration, intensity, skin color, tanning capacity
What is Fitzpatrick’s skin phototypes?
• Lists different skin types and how they tan/damage
Which type in Fitzpatrick’s skin phototypes is most susceptible to chronic photodamage (dermatoheliosis)?
- Type 1 will get the worst
- Pale skin, blue/hazel eyes, blond/red hair
- Always burns, does not tan
- Photodamage occurs mostly in types 1-3, and also 4 with heavy exposure
- SPT I and II make up 25% of the white population in the US
Which is the most damaging UV radiation?
UVB
Pathogenesis of chronic photodamage/dermatoheliosis
UVB is the most damaging UV radiation
Skin findings for chronic photodamage/dermatoheliosis
- Epidermal atrophy
- Wrinkles
- Telangiectasia
- Hypo/hyperpigmentation
- Solar lentigines
Microscopic appearance of chronic photodamage/dermatoheliosis
- Acanthosis hyperkeratosis
* Elastosis
Treatment for chronic photodamage/dermatoheliosis
- Protective sunblocks
- Change of behavior
- Topical sun-protective lotions
- SPT I and II persons should avoid the peak hours of sun 10-2:00
What is actinic keratosis?
- Sun induced dysplasia of the epidermis.
- Excessive exposure to UV radiation, particularly UVB.
- Males > females
- Middle aged or elderly
- Fair complexions that burn rather than tan
- 2-5% of cases develop an invasive squamous cell carcinoma. Numerous lesions for many years have higher risk.
- Predictor of risk for melanoma and other skin cancers.
2-5% of cases of Actinic keratosis develop this…
- Invasive squamous cell carcinoma
- Numerous lesions for many years have higher risk
- Predictor of risk for melanoma and other skin cancers
Appearance of actinic keratosis
- Erythematous or yellow-brown, flat, rough, scaly papules
- 2 mm to > cm
- Sun exposed surfaces: face and neck, dorsal hands and forearms
- Sun damaged of surrounding skin
Microscopic appearance of actinic keratosis
Epithelial dysplasia with alternating parakeratosis and orthokeratosis
Etiology for squamous cell carcinoma in situ
- Ultraviolet radiation
- Chronic arsenicism
- Immunosuppression
- Ionizing radiation, HPV, PUVA Rx
- 3-5% progress to invasive carcinoma
Treatment for squamous cell carcinoma in situ
- Excision
- Mohs micrographic surgery
- Histopathologic evaluation to exclude invasive SCC
What’s invasive squamous cell carcinoma?
- Malignant tumor of keratinocytes, arising in the epidermis
- Usually arises in epidermal precancerous lesions
- M>F, except legs
- Age of onset - >55 in the US
- 20s & 30s in Florida, Southwest, Southern California, Australia, New Zealand
- Incidence varies with sun exposure
- Continental US: 7-12/100,000
- Hawaii: 62/100,000 whites
Aggressiveness of invasive squamous cell carcinoma
- Aggressiveness varies with etiology and differentiation
- Sun induced lesions low rate of metastasis
- Immunosuppressed –> more aggressive more often metastasizes
Skin findings for invasive squamous cell carcinoma
- Indurated erythematous, yellowish or skin tone papule, plaque or nodule
- Keratotic scale
- Eroded or ulcerated, firm elevated margin
Etiology of invasive squamous cell carcinoma
- Ultraviolet radiation
- HPV
- Immunosuppression
- Chronic inflammatory and scarring conditions
- Industrial carcinogens
- Inorganic arsenic
