Exam 1 Week 1

Question 1

1. Identify multiple layers of skin 2. Functions of the skin (6)

Answer 1

1. Layers
   - Epidermis (stratum corneum, granulosa, spinosum, basale)
   - Dermis (fibrous tissues, hair follicle, blood vessels); papillary (superficial) and reticular dermis
   - Subcutaneous Tissue (adipose)
2. • Protects from environment • Immunologic organ (langerhan cells present antigens) • Regulates body temperature • Vitamin D metabolism • Sensory function • Cosmetic properties

Question 2

Identify microscopic lesions (part 1) 1. Diffuse epidermal hyperplasia 2. Abnormal, premature keratinization within cells below the stratum granulosum 3. Discontinuity of the skin showing incomplete loss of the epidermis 4. Infiltration of the epidermis by inflammatory cells 5. Intracellular edema of keratinocytes, often seen in viral infections 6. Hyperplasia of the stratum granulosum, often due to intense rubbing 7. Thickening of the stratum corneum, often associated with a qualitative abnormality of the keratin

Answer 2

1. Acanthosis 2. Dyskeratosis 3. Erosion 4. Exocytosis 5. Hydropic swelling (ballooning) 6. Hypergranulosis 7. Hyperkeratosis

Question 3

Identify microscopic lesions (part 2) 8. A linear pattern of melanocyte proliferation within the epidermal basal cell layer 9. Surface elevation caused by hyperplasia and enlargement of contiguous dermal papillae 10. Keratinization with retained nuclei in the stratum corneum. **It is normal On mucous membranes 11. Intercellular edema of the epidermis 12. Discontinuity of the skin showing complete loss of the epidermis revealing dermis or subcutis 13. Formation of vacuoles within or adjacent to cells; often refers to basal cell- basement membrane zone area

Answer 3

8. Lentiginous 9. Papillomatosis 10. Parakeratosis 11. Spongiosis 12. Ulceration 13. Vacuolization

Question 4

Identify disorders of pigmentation and melanocytes • Chronic depigmenting condition from SELECTIVE DESTRUCTION OF EPIDERMAL MELANOCYTES • Autoimmune hypthesis is favored -associated with other diseases like pernicious anemia and Hashimoto’s thyroiditis **Case 25-year-old woman presents with pale patches of skin around her mouth. They appeared a few months ago and have become more prominent. There is no itching, burning, or numbness in the patches. Vital signs are stable. PE reveals pale white patches symmetrically distributed around her mouth. The borders are well circumcsribed. Similar lesions are found over the areola of her breasts. She denies any trauma or infection. What is the pathology of her condition? **what areas most commonly seen? Presentation? Progression vs regression vs repigmentation?

Answer 4

VITILIGO; destruction of epidermal melanocytes • Autoantibody against melanin-concentrating hormone receptor 1 in serum. • Variable presentation, peaks in 2nd and 3rd decades. • Higher incidence in African Americans may be due to being more noticeable. • Predilection for acral areas (fingers, limbs), ears, and orifices (mouth, eyes, nose, anus)** • Presents as asymptomatic white macules with sharp borders that gradually enlarge** • Hair will also lose pigment • Can see the lesions better under a Wood’s lamp • Usually slowly progressive, but 10-20% experience spontaneous regression. • If repigmentation occurs, it begins around hair follicles that look like freckles and become confluent.

Question 5

Lesions with hyperpigmentation (4) 1. Melanocytes normal in number and morphology but melanin is increased in basal layers of epidermis 2. Acquired lesions. Small 3. 5 types (list) 4. 4 types (list)

Answer 5

1. Ephelis (freckle) 2. Lentigo/lentigines 3. Melanocytic nevi – Junctional – Compound – Intradermal – Dysplastic (Atypical) – Spitz 4. Melanoma – Superficial Spreading – Lentigo Maligna – Acral Lentiginous – Nodular

Question 6

1. Identify lesion of hyperpigmentation •Basal layer hyperpigmentation •Appear after sun exposure in lightly pigmented kids •Darken with sun exposure •No risk of malignancy

Answer 6

Freckle (Ephelis) **remember 4 lesions with hyperpigmentation (freckle, lentigo, melanocytic nevi, melanoma)

Question 7

Identify lesion with hyperpigmentation • Small (often <1.0 cm) circumscribed brown macular lesions • Elongations of rete (club shape) with hyperpigmentation of cells just above the basement membrane • Slight increase in basilar melanocyte density. Melanophages appear in the upper dermis

Answer 7

Lentigo/lentigines aka age/liver spot

Question 8

Identify lesion with hyperpigmentation

• Gross features – Tan to brown – Uniformly pigmented – Small (usually < 6mm in greatest dimension) – Flat to elevated – Well-defined, rounded borders

Histologic features – Sharply defined – Well nested at the dermal-epidermal junction – Melanocytes mature as they descend in dermis – No deep mitoses – No deep pigment in melanocytic nests ***Identify stages of progression

Answer 8

Melanocytic Nevi

Progression of maturation; Junctional - compound - Intraderma (dermal) - intradermal nervus with neurotization (extreme maturation)

1. Junctional nevus; Melanocytes nests at the dermal-epidermal junction. Nests are restricted to the tips and sides of rete
2. Compound; More raised and dome shaped than junctional nevus. With increasing depth, they mature and become smaller. **Intraepidermal nevus cell nests + nests and cords of nevus cells in underlying dermis
3. Intradermal (derma); epidermal nests are lost completely
4. Spitz nevus; KAMINO BODIES (basement membrane marterial) - eosinophilic bodies along dermal -epidermal junction (deep red color and common in children)

Question 9

Summarize the 5 types of melanocytic nevi versus the 4 types of melanoma

Answer 9

1. Melanocytic nevi – Junctional – Compound – Intradermal – Dysplastic (Atypical) – Spitz 2. Melanoma – Superficial Spreading – Lentigo Maligna – Acral Lentiginous – Nodular

Question 10

Identify condition - tendency to occur in kids. Red raised nodule - KAMINO BODIES (eosinophilic basement membrane material); along dermal-epidermal junction • Sharply defined laterally • Line symmetry from left to right • Clefts help separate the nests from keratinocytes/epidermis • Clinical: **common in what age group? Mistaken for what?

Answer 10

Spitz Nevus

**Nest of melanocytes are found within the epidermis and are separated from epidermis via clefts – Common in children – Deep red color, may be mistaken for hemangioma**

Question 11

Identify condition (subtype of hyperpigmentation of lesion) – Commonly large, oval, and multiple – Irregular pigment common – Fading border or fried-egg appearance (central papule, surrounding macule) – Histologic: Usually compound, concentric papillary dermal fibrosis – Horizontally oriented nests with bridging of adjacent rete – Nests are at the tips and sides of rete – Cytologic atypia: hyperchromatic, enlarged nuclei **what is restricted to junctional component?***

Answer 11

Dysplasia (atypical) melanocytic nevus) ** ATYPIA is restricted to junctional component; no confluence or significant pagetoid scatter, and dermal melanocytes are banal appearing

Question 12

Identify lesion of hyperpigmentation • Malignancy of pigment-producing cells (melanocytes which are derived from the neural crest) • Develops de novo or from a pre-existing mole • Found in the skin, eyes, GI tract, leptomeninges, oral and genital mucosa** • 4% of all skin cancers • #1 cause of skin cancer deaths worldwide **Most frequent cancer in what gender/race? **4 subtypes **2 growth phases **does it metastasize? Where to?

Answer 12

1. MELANOMA • Incidence is increasing more than any other neoplasm • Lifetime probability in US: 1 in 37 for men, 1 in 56 for women • Most frequent cancer in white women aged 25-29 years**** • Subtypes:*** 1. Superficial spreading 2. Lentigo maligna 3. Nodular 4. Acral Lentiginous • Radial and Vertical growth phases • Melanoma is third most common metastatic tumor to the brain after lung and breast cancer

Question 13

Summarize 4 subtypes of melanoma

**Describe progression

Answer 13

1. Superficial spreading 2. Lentigo maligna 3. Nodular 4. Acral Lentiginous

Question 14

Risk factors for melanoma **what is a sign of >400x the relative risk **what conver 500 to 1000 fold greater risk of developing melanoma ** What are 2 universal risk factors for melanoma?

Answer 14

– A CHANGING MOLE is >400X the relative risk • Clinically atypical/dysplastic nevi (particularly >5-10) • Numerous common nevi • Large (giant) congenital nevi (>20 cm diameter in an adult) • Previous melanoma or prior nonmelanoma skin cancer • Sun sensitivity/history of excessive sun exposure • Melanoma in first-degree relative(s): especially if 2 or more • Xeroderma pigmentosum or familial dysplastic nevus syndrome: confer a 500- to 1000-fold greater relative risk of developing melanoma*** ** Fair skin and the history of blistering sunburn(s) in childhood and adolescence are universal risk factors for melanoma

Question 15

How to manage suspicious lesions for melanoma 2 ways

Answer 15

• Use the simple ABCDE rule of skin lesions – Asymmetry, Border irregularity, Color variation, Diameter > 6mm, Evolving **Lots of melanoma are however smaller than 6mm • Avoid too superficial of a biopsy; if suspected excisional biopsy is best for staging **If you suspect melanoma, make sure the biopsy is deep enough. The excisional biopsy is best to get down to the fat for staging?

Question 16

Identify radial and vertical growth phases of melanoma - which is in the epidermis and papillary dermis ? - which go deeper into dermal layers ?

Answer 16

• RADIAL growth phase – Horizontal spread of melanoma cells within the epidermis and papillary dermis • VERTICAL growth phase – Tumor cells invade downward into deeper dermal layers as a mass – Greater metastatic potential – Invading cells do not mature as in melanocytic nevi

Question 17

Melanoma subtypes – MOST COMMON (50-75% of all melanomas) – 25% from pre-existing lesion, others de novo – Sun-exposed skin, typically on BACKS OF MEN and lower LEGS OF WOMEN but any age, any place – Radial growth phase of uncertain length (but faster than Lentigo maligna) before vertical growth phase develops – Evolved lesions may show multiple shades: red, tan, brown, blue, black , grey and white **Identify histology features - is it symmetric? Regular? - are deep mitoses present? - what is often marked?

Answer 17

SUPERFICIAL SPREADING malignant melanoma Histology features; **One side don’t look like other side (BORDER IRREGULARITY) • Melanocyte confluence with buckshot scatter of atypical melanocytes within the epidermis (pagetoid spread) • Typically not symmetrical (R to L) • Typically fails to mature from top to bottom (dermal component looks like the junctional component) • Mitoses including deep mitoses may be present • CYTOLOGIC ATYPIA often marked**

Question 18

Melanoma subtype – Often slow-growing lesion – Typically, face (head and neck) of old men, but women also affected*** – Sometimes long radial growth phase, 10-50 years – Starts as tan-brown macule**, gradually enlarges, develops darker, asymmetric foci **Some Evolve into what?

Answer 18

LENTIGO MALIGNA – Some lesions evolve to become clinically palpable, signaling dermal invasion and transformation into LENTIGO MALIGNA MELANOMA (5 – 15% of melanomas)

Question 19

identify condition of hyperpigmentation

**2 forms - differentiate

Answer 19

1. Lentigo maligna – Broad lesion on sun-damaged skin – Predominantly JUNCTIONAL growth of atypical melanocytes** – Cytologic atypia – Distinguishing features • Malignant melanoma in situ • Poorly nested and confluent melanocytes at the dermal- epidermal junction • Adnexal extension • Heavily sun-damaged skin (severe solar elastosis present)
2. Lentigo maligna melanoma – Lentigo maligna with invasion

Question 20

Melanoma subtype

– Least common, < 5% of all melanomas – Most common melanoma in African Americans and Asians – Palms, soles, beneath the nail plate

**what sign do you look for?

Answer 20

Acral lentiginous melanoma

**palms, soles, subungal

**Look for Hutchinson’s sign

Question 21

Melanoma subtype – 15-30% of melanomas – Anywhere on the body** – Can be amelanotic – Histology • Vertical growth phase melanoma • No apparent radial growth phase • Dermal growth occurs in isolation or, occasionally, in association with a minor epidermal component • Mitoses are frequent and often atypical

Answer 21

NODULAR melanoma

Question 22

Tumor thickness measurement 2 reported ways of measurement 1. Which is actual measurement from the skin surface? 2. Which is not based on measurement but on number of layers of skin that tumor can penetrate? **which closely correlates with survival stats?

Answer 22

2 reported ways of measurement - 1. BRESLOW is the actual measurement from the skin surface ** Breslow’s measurement most closely correlates with survival statistics (measured in mm from granular cell layer) 2. CLARK level is not based on a measurement, but on the number of layers of skin that the tumor has penetrated (I-V) I: epidermis II: papillary dermis, not yet to papillary-reticular junction III: fills papillary dermis IV: reticular dermis V: subcutaneous tissues

Question 23

What test would you use for this conditions • Lymphoscintigraphy, radioactive tracer and a gamma probe is used • Recommended for INTERMEDIATE TUMORS (1 to 4 mm thickness) or HIGH-RISK THIN tumors (i.e. ulcerated) • Minimally invasive technique that has been shown to help accurately stage the regional nodal basin with a lower associated rate of complications and costs compared to ELND • Subsequent full lymph dissection is performed if metastatic disease is present and adjuvant therapy may be administered

Answer 23

Sentinel node biopsy

Question 24

Identify 6 key prognostic factors (2 major ones)

Answer 24

• Tumor thickness • Mitotic rate • Ulceration • Lymph node involvement • Satellite lesions • Distant metastases **TUMOR THICKNESS and ULCERATION are 2 major ones

Question 25

Prognoses in terms of staging (survival rate in %) Stage I and II III (depends on what 2 prognostic factors) IV

Answer 25

• Stage I and II: 5-year survival rate of 50-90+% • Stage III: Dependent on NODAL INVOLVEMENT and ULCERATION, 5-year survival rate of 40-80% • Stage IV: 5-year survival rate of 15-25%

Question 26

Case A 25-year-old woman presents to your office with a mole on her left calf that has changed in color and shape recently. You tell her that you are suspicious for what type of skin cancer? You tell her that you need to get a biopsy of the lesion. The medical student that is working with you asks if a superficial shave biopsy will be sufficient and your answer is?

Answer 26

1. Malignant melanoma 2. No, prognosis largely depends on thickness/depth of invasion of malignant melanocytes

Question 27

Benign epithelial tumors • The MOST COMMON BENIGN tumor in older individuals (40+ yrs) • Begin as light brown, flat macules • Later they develop a velvety or waxy to finely verrucous surface • Color may vary from pale brown with pink tones to dark brown or black • Typically have an appearance of being stuck on the skin surface and crumble with scraping **WHAT IS LESER TRELAT SIGN? **what test should you do if you thick its melanoma

Answer 27

Seborrheic keratosis • The sign of Leser-Trélat is the association of multiple eruptive seborrheic keratoses with internal malignancy • Biopsy if suspicious for melanoma

Question 28

Identify histologic features of what benign epithelail tumor?

PIGMENTED OR NOT? What type of cysts? What is in the cyst?

Answer 28

Seborrheic keratoses

• Exophytic • Show sheets of small, basaloid cells • Frequently pigmented • Exuberant keratin production at surface • Small keratin-filled cysts known as horn cysts • Loose lamellar “shredded-wheat” or “onion- skin” keratin

Question 29

Benign tumor - subtype of SK • Brown to black, smooth, dome-shaped papules • Can be numerous • Most often seen in African Americans • Sub-type of seborrheic keratosis

Answer 29

Dermatosis Papulosa Nigra

Question 30

Benign epithelial tumor • Hyperpigmentation is first sign • HYPERPLASIA of STRATUM SPINOSUM makes skin thick and velvety • Usually found in folds of the neck, axilla, and groin**** • 80% are BENIGN type; usually occurs in childhood or puberty; may be associated with endocrine abnormalities (example: DIABETES MELLITUS)*** • MALIGNANT type occurs in middle-aged and OLDER, associated with visceral malignancy • May be early indication underlying disorder

Answer 30

ACANTHOSIS NIGRICANS; Brown pigments on folds of neck, axilla and groin (makes skin thick and velvety due to hyperplasia of stratum spinosum) **If you see this in young patient, work them up for DM

Question 31

17-year-old young man comes to the office for evaluation of a skin lesion. For the past 2 mos, he noticed darkening and thickening over his neck and groin area. These areas occasionally feel itchy. PE reveals symmetrical hyperpigmented velvety plaques on the axilla, groin, and posterior neck. This should alert the physician to?

Answer 31

Diabetes mellitus

Question 32

• A top 10 benign lesion • Inflamed vs. “quiet” • Histologic: Cyst wall resembles normal epidermis, filled with strands of keratin • When ruptures, granulomatous inflammation

Answer 32

Epidermal (inclusion) cyst aka Sebaceous cyst **elevation/nodule that look like cyst when taken out (cheesy content inside)

Question 33

Premalignant/malignant epidermal tumors - dysplasis of keratinocytes • ***Earliest identifiable lesion that can develop into squamous cell carcinoma (SCC); Up to 60% of SCCs develop from this conditions. Patient with 10 or more of this condition have 10-15% chance of developing SCC • Risk factors: years of sun exposure, fair skin, immunosuppression **key to diagnosis? **Found in what body areas?

Answer 33

ACTINIC KERATOSIS • Palpation is key to early diagnosis • Initially may be hard to see but will have areas of rough or “gritty” skin • Discrete, scaly, feels like “broken glass,” surface lesion • Develop into poorly-demarcated, slightly erythematous papule or plaque with adherent scale • Commonly found on sun exposed areas: face, scalp, ears, posterior neck, forearms and legs**

Question 34

Histologic features of actinic keratosis

Answer 34

• Parakeratosis (retained nuclei) in stratum corneum • Hyperplasia and cytologic atypia of lower 1/3 • Solar elastosis in superficial dermis **lower third of lesion has atypia

Question 35

A 85-year-old widowed white man comes to the office for his yearly check-up. He complains of red crusty bumps on his forehead. These lesions are also located on the back of his hands and on his scalp. He spent the last year in Florida and refused to wear any sunscreen because he wanted to be tan for the ladies. He has tried different moisturizing lotions for the bumps without improvement. What is the most likely diagnosis? What common skin cancer could develop?

Answer 35

Actinic keratosis ** Squamous cell carcinoma

Question 36

• Most common cancer in the US about equal to all other cancers combined **identify the 2 main types

Answer 36

Nonmelanoma Skin Cancer (NMSC) 1. SCC (20%) 2. BCC (80%) ** After developing an initial BCC or SCC, patients have approximately a 50% chance of developing another NMSC within 5 years

Question 37

Patient present with non melanoma skin cancer that occurred from actinic keratosis. Identify; - - various or single morphology? - risk factors? - most important cause? - common in what body areas

Answer 37

• SCC may present as a variety of primary morphologies with or without associated symptoms • Risk factors: Male, elderly, UV and ionizing radiation, fair skin, arsenic, HPV, sites with chronic infection, thermal burn scars and immunosuppression BUT • MOST IMPORTANT cause is DNA damage induced by exposure to UV light: #1 UVB, #2 UVA • Common on the scalp, dorsal upper extremities, and ears

Question 38

• Can present with a scaly pink patch or a thin keratotic papule • BOWEN DISEASE is a subtype characterized by a sharply demarcated pink plaque and can arise on non-sun-exposed skin **What is Bowen disease of the glans penis called? **IDENTIFY clinical and histologic finding

Answer 38

SCC in situ • Erythroplasia of Queyrat: Bowen disease of the glans penis, which manifests as one or more velvety red plaques • CLINICAL: Circumscribed erythematous scaly plaque. Pigmented variant exists. • HISTOLOGY: – May be flat or acanthotic or papillomatous with HYPERPARAKERATOSIS. – Constant features are full thickness KERATINOCYTES ATYPIA and loss of normal maturation. – May replace adnexal structures (folliculo-sebaceous units) – Pagetoid variant exists. **mitotic activity in spinosum

Question 39

Histology slide of SCC in situ ( 3 points)

Answer 39

SCC in situ • Atypia keratinocytes of epidermis • Hyperkeratosis on top (red and dead keratinocytes) • Mitotic activity in spinosum

Question 40

Identify the following based on histologic features 1. • NO invasion through basement membrane of dermoepidermal junction • ATYPICAL NUCLEI (enlarged and hyperchromatic) involve all levels of the epidermis 2. • Invade basement membrane • Variable differentiation – Orderly lobules of polygonal cells, areas of keratinization (well differentiated) – Anaplastic cells, necrosis, no organized keratin production (poorly diffentiated)

Answer 40

1. SCC in situ (Bowen disease) 2. SCC

Question 41

• Raised, firm, pink-to-flesh colored keratotic papule or plaque arising on sun-exposed skin • Surface changes may include scaling, ulceration, crusting, or the presence of a cutaneous horn **IDENTIFY Subtypes? Metastasis?

Answer 41

Invasive SCC • SUBTYPES include oral and verrucous (resemble large warts) • METASTASES to regional lymph nodes < 5%, generally by deeply invasive tumors

Question 42

Clinical and Histology features of invasive SCC

Answer 42

Invasive SCC • CLINICAL: Hyperkeratotic papules or plaques upon sun-damaged skin. • HISTOLOGY: – Atypical keratinocytes invading the dermis. – Well vs Moderately vs Poorly Differentiated – Variants; Keratoacanthoma, Acantholytic, Verrucous

Question 43

Diagnosis of SCC - require what test for definitive diagnosis? - what skin layer must you reach to be able to determine the presence or absence of invasive disease? - what must be performed if regional lymphadenopathy is present? - what 3 tests help offer a good chance of detecting subclinical nodal metastasis in high-risk pts - rate of metastasis? - survival rate?

Answer 43

• Definitive diagnosis of NMSC requires a biopsy (shave, punch, incisional, or excisional) • Must reach at least the depth of the mid dermis to allow for a determination of the presence or absence of invasive disease • Lymph node biopsy or FNA should be performed if regional lymphadenopathy is present • PET scanning, ultrasound-guided FNA, and Sentinel lymph node biopsy all appear to offer a good chance of detecting subclinical nodal metastasis in high-risk pts • Metastasis for squamous cell carcinoma is in the range of 2-6% but can be much higher with high-risk lesions • 5-year survival rate of patients with nodal metastasis is as high as 73% with aggressive treatment

Question 44

What is a look alike of SCC - Appear suddenly on actinically-damaged skin, grow rapidly and spontaneously regress after a few months • Red to flesh colored dome-shaped papule with a central crater filled with keratinous plug • Pathologists have trouble differentiating the two • Many treat the same as SCC ** Can they ever transform into SCC? What age group? Histology?

Answer 44

Keratoacanthoma (KA) **Has preprogrammed cell involution • May transform into SCC (more common in older patients 80+) • May be well-differentiated SCC and most treat as such; evidence however suggests it is an abortive squamoproliferative lesion which mimics squamous cell carcinoma Histology - Large, red, glassy squamoid cells - Cellular atypia mild and mitoses uncommon - Neutrophil microabscesses common - Eosinophils and lymphocytes are common in surrounding infiltrate

Question 45

• MOST COMMON MALIGNANCY • Annual incidence in US is ~1 million cases • Estimated lifetime risk in the white population is 33-39% in men and 23-28% in women. • Pluripotential cells in the basal layer of the epidermis or follicular structures ** - rate of growth? Metastasis? - cause what if neglected? - prognosis?

Answer 45

Basal cell Carcinoma (NMSC) • Slow growing and rarely metastasizes • Can cause local destruction and disfigurement if neglected or inadequately treated • Prognosis is excellent with proper therapy

Question 46

BCC - Risk Factors? (Most important one?) - presentation? - found in what body areas? - subtypes (4)

Answer 46

• Risk factors: UV radiation (most important risk factor), x-ray, arsenic, immunosuppression, a number of hereditary syndromes and prior history of NMSC • Often present with a non-healing lesion that bleeds, pearly papule or “rodent ulcer” • Commonly found on the face, ears, scalp, neck, or upper trunk • Subtypes include: nodular, superficial and infiltrative/morpheaform, other rare subtypes

Question 47

BCC subtype - Young age – Autosomal dominant; mutations in PTCH (Patched) gene on chromosome 9q. – Abnormal facies, multiple BCCs, skeletal abnormalities, odontogenic keratocysts, calcification of flax cerbri.

Answer 47

• Nevoid basal cell carcinoma syndrome (Gorlin- Goltz syndrome)

Question 48

BCC subtype - most common BCC subtype - most common body site? - classic signs? - what happens when person has minor trauma?

Answer 48

Nodular- most common type (60% of BCCs) – FACE is most common site – Waxy papules with central depression – PEARLY appearance – Erosion, ulceration or crusting – Bleeding with minor trauma – ROLLED (RAISED) BORDER* – Translucency – TELANGIECTASIAS over the surface*

Question 49

BCC subtype - second most common subtype - common site? - color?

Answer 49

Superficial – Second most common subtype (30% of BCCs) – TRUNK is most common site – Slightly scaly papule or plaque – Light red color – Atrophic center with fine translucent micropapules on rim

Question 50

Diagnosis of BCC - What type of biopsy? (2)

Answer 50

• Biopsy is required to confirm the diagnosis and to identify the histologic subtype • SHAVE or PUNCH biopsy is usually performed

Question 51

Histology of BCC - what is at border of nest - where are the nests - some tumor nests/nodules attach to what skin layer? - do stroma and tumor nodules separate or come together?

Answer 51

BCC (they are slow growing and metastases is very rare. Problems they cause relate to local invasion) • Variable Histologic Morphology •

Question 52

Histology of BCC **3 classic features

Answer 52

BCC The cells of a basal cell carcinoma are dark blue and oblong with scant cytoplasm. They resemble the cells along the basal layer of normal epidermis. **classic features Blue basaloid cell nests (blue) Peripheral palisading (red) Fibromyxoid stroma (grey)

Question 53

Histology of BCC Classic features

Answer 53

BCC Blue basaloid cell nests Peripheral palisading Stroma separating from tumor nodules (red)

Question 54

**Identify careful treatment of NMSC • Removal of tumor and a thin rim of normal appearing skin around the defect • Specimen is sectioned and labeled • Frozen-section technique allows for an examination of tissue while the patient is in the office • If margins are not clear further excision will be done and normal tissue will be spared • Best long-term cure rates of any treatment modality

Answer 54

Mohs surgery **Doing frozen sections as they do the surgery to minimize the amount of tissue excised in cosmetic areas (face) **Go stage by stage and take tumor out with clear margins

Question 55

A 71-year-old fair-skinned man presents to the clinic with a red, crusty lesion on his right temple. The lesion has been present for over a year and seems to be getting worse. On physical exam you are suspicious that the lesion is one of two common non-melanoma skin cancers. On palpation of the cervical lymphatics you find a few enlarged nodes. Which of these common skin cancers is more likely to metastasize?

Answer 55

Squamous cell carcinoma **Most likely metastasize. Basal hardly Mets (would be highly fatal when/if they do) Invasive SCC • Raised, firm, pink-to-flesh colored keratotic papule or plaque arising on sun-exposed skin • Surface changes may include scaling, ulceration, crusting, or the presence of a cutaneous horn • Subtypes include oral and verrucous (resemble large warts) • Metastases to regional lymph nodes < 5%, generally by deeply invasive tumors

Question 56

A 76-year-old fair-skinned man presents to the clinic with a lesion located on the left side of his chin. It has been present for 6 months and seems to bleed very easily while shaving. It is a 1 cm pearly papule with central hemorrhagic crust and peripheral telangiectasias. Most likely diagnosis?

Answer 56

Basal cell carcinoma • Nodular- most common type (60% of BCCs) – Face is most common site – Waxy papules with central depression – Pearly appearance – Erosion, ulceration or crusting – Bleeding with minor trauma – Rolled (raised) border – Translucency – Telangiectasias over the surface

Question 57

Tumors of the dermis • Aka Benign Fibrous Histiocytoma • Very common benign lesion that most often occurs on the lower legs • Slow growing; single or multiple • Flesh-colored to pigmented papule • Displays the “dimple-sign” in which it depresses when squeezed • Can be pruritic but usually asymptomatic • Can leave it alone or remove it with punch biopsy **HISTOLOGY

Answer 57

DERMATOFIBROMA Aka Benign Fibrous Histiocytoma **mostly in legs • Benign proliferations of fibroblasts with collagen • Higher magnification shows whirling (aka pinwheel or storiform) fibroblasts with collagen bundles • May be overlying hyperkeratosis and hyperpigmentation, giving them a reddish brown color **EPIDERMAL INDUCTION AND COLLAGEN BALLS

Question 58

– Primary intermediate grade sarcoma of skin – Locally aggressive but RARELY METASTASIZES – Hypercellular – Overlying epidermis is thinned – Extends from dermis into subcutaneous fat in a “honeycomb” pattern – Fibroblasts in pinwheel pattern

Answer 58

Dermatofibrosarcoma protuberans **tumor of dermis

Question 59

• Slow growing, trunk and extremities, young adults • Local recurrence common, rare metastases • Bland storiform spindle cell proliferation • Honeycomb pattern in fat • Minimal mature collagen • Cytogenetics t(17;22)

Answer 59

Dermatofibrosarcoma protuberans (DFSP) CD34+

Question 60

Disorders of epidermal maturation 2 types of this (disorder that impair epidermal maturation) **Which comprise of most cases

Answer 60

ICHTHYOSIS (build of stratum corneum) 1. Congenital (most cases) – Congenital ichthyosiform erythroderma (AR) – Lamellar ichthyosis (AR) – X-linked ichthyosis – Ichthyosis vulgaris (AD or acquired) 2. Acquired – Ichthyosis vulgaris – associated with lymphoid and visceral malignancies

Question 61

• All forms have build up of compacted stratum corneum with loss of basket-weave pattern **2 outcomes of stratum granulosum

Answer 61

ICHTYOSES • Stratum granulosum normal to slightly thickened: – lamellar – x-linked – congenital ichthyosiform erythroderma • Stratum granulosum thin or absent: – ichthyosis vulgaris

Question 62

Acute inflammatory dermatoses **Histology - causes of rashes? (5)

Answer 62

This is a skin rash. There are many causes for rashes, including topical irritants, ingestion of drugs, infections, viral, and allergic reactions.

Question 63

IDENTIFY acute inflammatory dermatoses • Wheals (pruritic papules to edematous plaques) • From mast cell degranulation and subsequent microvascular hyperpermeability • Lesions develop and disappear within hours but episodes may last for days to weeks **IDENTIFY; common sites and pathogenesis?

Answer 63

URTICARIA (HIVES) • Common sites: trunk, extremities • Pathogenesis: – Antigen-induced mast cell degranulation through sensitization with specific IgE antibodies – Follows exposure to multiple antigens: pollens, foods, drugs, insect venom

Question 63

Histology of urticaria - infiltrate? - cell types? (Early and then late?); which is really important

Answer 63

Subtle histologic changes - Superficial dermal PERIVENULAR INFILTRATE, neutrophils early then mononuclear cells and EOSINOPHILS are often seen - Collagen bundles more widely spaced due to dermal edema - Dilated lymphatics from absorption of edema fluid - Usually no epidermal changes **No epidermal change - every thing happens in the DERMIS

Question 63

Identify acute inflammatory dermatoses • Inflammatory reaction caused by an exogenous chemical. • Two forms: irritant and allergic • Irritant is produced by a substance that has direct toxic effects on the skin. (Ex. acids, detergents, alkalis, frequent hand washing) • Not an immunologic condition • Rash begins shortly after exposure **SUBCATEGORIES? (4 MAIN*)

Answer 63

CONTACT DERMATITIS • Subcategories – Allergic contact dermatitis* – Primary irritant dermatitis* – Atopic dermatitis* – Drug-related eczematous dermatitis – Photoeczematous dermatitis – Dyshidrotic Eczema – pruritic vesicles and papules on palms, fingers and soles of feet – Stasis dermatitis*

Question 64

IDENTIFY WAYS you can get IRRITANT contact dermatitis (3)

Answer 64

1. Lip licking 2. At colostomy site 3. Frequent hand washing

Question 65

Type of dermatitis • Cell-mediated, delayed-type hypersensitivity reaction (Type IV) – Ag on skin surface taken up by Langerhans cells – Migrate via dermal lymphatics to lymph nodes – Present Ag to CD 4+ (helper)T cells which become effector and memory cells • Sensitization of skin occurs 1-2 wks after 1st exposure to allergen • Reexposure causes dermatitis in hours to days • Common allergens: poison ivy, mangos, iodine, nickel, rubber, cosmetics

Answer 65

Allergic contact dermatitis **Temporary tatoo on the back • Poison ivy, poison oak, poison sumac (Rhus dermatitis)*** • Produce urushiol as common allergenic substance • Fluid contained in vesicles does not contain an allergen and cannot induce disease in others - This person contacted a plant in a tropical jungle to which he was already sensitized. A couple of days later, the skin is red from inflammation and slightly raised from local edema; This is contact dermatitis, a form of type IV hypersensitivity reaction that is localized.

Question 66

Differences btw irritant and allergic dermatitis - MoA - Onset - Incidence - lesion

Answer 66

1. Irritant MoA; direct effect Onset; few hours Incidence; anyone Lesion; erythema vesicles crust 2. Allergic MoA; type IV Onset; 12-72 hours Incidence; only sensitized persons Lesion; erythema papules vesicles scale

Question 67

Contact dermatitis 1. Clinical features 2. Diagnosis 3. Treatment

Answer 67

1. Clinical features: • Erythematous papules and vesicles with oozing-> ->->crusting and scaling • Very pruritic 2. Diagnosis made clinically based on H&P. This is where job, hobbies, etc. become important. Patch testing to identify allergen if: 1) The diagnosis is in doubt. 2) Rash not responsive to treatment. 3) The rash recurs. 3. Treatment: • Avoid the allergen/irritant!!! • Apply cool water compresses. • Antihistamines for itch. • Apply topical steroids. • Systemic steroids for severe cases.

Question 68

Atopic dermatitis 1. Presentation 2. Clinical features 3. Treatment 4. Result

Answer 68

1. Chronic , waxing and waning, extremely pruritic, condition beginning in 1st year of life • Look for family hx of allergies, asthma, and eczema • Condition is worse in winter due to decreased humidity. • Etiology is multifactorial 2. Papules, vesicles, oozing, and crusting. • Distribution is age dependent. Babies get it on face, diaper area and extensor surfaces of extremities. Children and adults get it on neck, face, axillae, antecubital and popliteal fossas. • Despite oozing, skin is very dry. 3. Itching -> scratching -> itching Treatment involves: Itching – antihistamine, Dryness – moisturizer, Inflammation – topical steroids 4. Chronic dermatitis can lead to • LICHENIFICATION - EPIDERMAL thickening, characterized by visible and palpable skin thickening with accentuated skin lines

Question 69

Type of spongium dermatitis • “coin-shaped” • Itchy red plaques with vesicles and distinct borders • More likely in young adults • Same treatment as for atopic dermatitis

Answer 69

Nummular dermatitis

Question 70

Type of dermatitis • “Winter itch” • Older people in winter • Dry, cracked skin that becomes itchy **identify treatment

Answer 70

Asteatotic dermatitis Tx: Avoid excessive bathing Use room humidifiers Moisturizers Topical steroids if inflamed

Question 71

Identify type of dermatitis A. Dermal edema and perivascular infiltration by inflammatory cells B. 24-48 h: Epidermal spongiosis and microvesicle formation C. Abnormal scale, parakeratosis, progressive acanthosis (subacute) D. Hyperkeratosis E. Chronic lesion **2 types

Answer 71

Evolution of SPONGIOTIC DERMATITIS • Acute spongiotic dermatitis (Acute Eczematous Dermatitis) – Spongiosis (intercellular edema); initial stages - separation of keratinocytes from each other – Exocytosis of lymphocytes • Subacute spongiotic dermatitis – Parakeratosis; retention of nuclei? – Acanthosis (thickening of skin) – Spongiosis (intercellular edema) – Exocytosis of lymphocytes

Question 72

5 types of WBCs in the blood **3 granulocyte and 2 agranulocytosis - which is most abundant - what cells are dominant in acute inflammation? Chronic inflammation?

Answer 72

1. Polymorphonuclear neutrophils (62); can’t be stained 2. Polymorphonuclear eosinophils (2.3); stain red 3. Polymorphonuclear basophils (0.4); stain blue 4. Monocytes (5.3) 5. Lymphocytes (30) **Acute inflammation; NEUTROPHILS infiltrate (innate immunity) - quick generic response **Chronic inflammation; LYMPHOCYTES (adaptive immunity) - specific response try to remove bacteria

Question 73

Macrophages vs neutrophils vs mast cells 1. What is first line of defense? 2. Second line of defense? 3. Third? (Remove pus) 4. Fourth ? (Increased production of what 2 cell types) 5. What do activated Mac and T cells produce in inflamed tissues? ** 3 important cells in acute inflammation

Answer 73

1. TISSUE MACROPHAGE is the first line of defense: immediate (mins). Call for help if overwhelmed 2. NEUTROPHILS infiltration to the infected tissues is the second line of defense: within a few hours (24 hours). PUS if formed 3. A second MACROPHAGE invasion of the inflamed tissue is the third line of defense: within days (2-3 days) due to the increased bone marrow production of monocytes. 4. Greatly increased production of both granulocytes and monocytes by bone marrow is the fourth line of defense (takes at least 3-4 days to make/leave bone marrow). 5. Activate mac and t cells produce TNFa, IL-1, GM-CSF, G-CSF, and M-CSF in the inflamed tissues. **Macrophages, neutrophils and mast cells

Question 74

1. Anatomy of human skin 2. Skin infections in order of skin layer

Answer 74

1. A. Epidermis - stratum corneum; cornfield layer (flattened, fused cell remnants) - stratum granulosum (lamellar granules) - stratum spinosum (keratinocytes) - stratum basale; stem cells present here 2. A. ERYSIPELAS; epidermis B. CELLULITIS; dermis (post capillary venule, subcutaneous fat) C. NECROTIZING FASCIITIS; deeper dermis (close to deep fascia) D. MYOSITIS; muscle involved

Question 75

1. Acute inflammation caused by what 2 stimuli 2. 3 important cells in acute inflammation 3. 5 neutrophil chemotactic factors. Come from where? 4. Where do mast cells reside? - what is in granules - what activate mast cells (2) - what do mast cells make?

Answer 75

1. 2 things that cause acute inflammation A. Infections B. TISSUE NECROSIS; pyknosis, karyolysis and karyorrhexis 2. Neutrophils, mast cells and macrophages; required in acute inflammation 3. Neutrophils come from blood. 5 neutrophil chemotactic factors are; C5a, IL-8, leukotriene B4 (LBT4), and bacterial products 4. MAST CELLS reside in loose connective tissue in dermis - lots of SECRETORY GRANULES. Present in granules are; histamine, NCF, ECF-A. All cause immediate acute inflammation. **You pre make these and store in the granules which are released by degranulation when needed - Mast cells are activated by; 1) tissue trauma; 2) C3a and C5a; and 3) IgE - Mast cells also make newly synthesized chemicals, slow-reacting substance of anaphylaxis (SRS-A), a mixture of leukotrienes (LTs) LTC4, LTD4 and LTE4 (vasodilation), and prostaglandins (PGs) (pain)

Question 76

Factors that mediate acute inflammation 1. Arachidonic acid produce what 2 things 2. What 2 things act on arachidonic acid 3. What does COX produce? What is the effect of the products on arterioles and veins? 4. What produce LTs? Functions of LTs? 5. What receptor is present on the cells of innate immune system - what do they recognize? - what is present mac which recognizes LPS of GNB along with TLR4 to upregulate the NF-kB resulting in acute inflammation. - what is the receptor for peptidoglycan?

Answer 76

1. Arachidonic acid, released from phospholipid cell membrane by phospholipase A2, is the starting material in the synthesis of two kinds of essential substances, the PROSTAGLANDINS (PGs) and the LEUKOTRIENES (LTs), both of which are also unsaturated carboxylic acids. 2. Cyclooxygenase or 5-lipoxygenase acts on arachidonic acid. 3. Cyclooxygenase produces PGs (PGI2, PGD2 and PGE2), resulting in arteriolar dilation (VASODILATION) and increased vascular permeability (POST-CAPILLARY VENULE) 4. 5-Lipoxygenase produces LTs. - LTB4 attracts / activates neutrophils. - LTC4, LTD4 and LTE4 causes smooth muscle contraction. 5. TLRs are present on the cells of innate immune system (macrophages and dendritic cells) - TLRs recognize Pathogen Associated Molecular Patterns (PAMPs) - CD14 are percent on Mac and recognize LPS and TLR4 - unregulated NFkB which result in acute inflammation - TLR2 is the receptor for peptidoglycan

Question 77

Physiologic events of acute inflammation (Memorize) 1. What cause arteriolar dilation 2. What happens with capillary congestion 3. Explain WBC margination - what does histamine mediate - what does TNFalpha and IL1 induce - what does selectin bind to on leucocytes - what binds to adhesin molecules? - what does TNFalpha and IL1 regulate? 4. What escape into interstitial space

Answer 77

1. Pronounced arteriolar dilation due to smooth muscle relaxation, increased blood flow into capillary bed (post-capillary venues). 2. Capillary congestion with increased capillary hydrostatic pressure (filtration force) 3. Sludging of blood into the dilated capillary with WBC margination. a) P-selectin of Weibel–Palade bodies is mediated by histamine b) E-selectin, induced by TNFa and IL-1 c) Selectins binds to sialyl-Lewis X (SLex) on leucocytes. d) Integrins, upregulated by C5a and LTB4, binds to adhesion molecules (ICAM-1 and VCAM-1) e) ICAM and VCAM, regulated by TNFa and IL-1 4. Endothelial cell retraction, proteins/cells escape into interstitial space. Increase tissue (interstitial fluid) colloid osmotic pressure (filtration force) **Among proteins that escape are complement

Question 78

Types of skin lesions 1. due to proliferation of organisms, usually viruses, within the epidermis. Examples? 2. Large blister due to toxin. caused by toxin-producing organisms 3. Impetigo caused by either Streptococcus pyogenes (impetigo contagiosa) or Staphylococcus aureus (bullous impetigo) 4. Localized infection of hair follicles usually due to S.aureus 5. Raised lesions of the skin occur in many different forms and can be caused by? 6. can be caused by cutaneous anthrax, ulceroglandular tularemia, plague, and mycobacterial infection. 7. abrupt onset of fiery red swelling of the face or extremities, with well-defined indurated margins, intense pain, and rapid progression. **What is the exclusive cause?

Answer 78

1. VESICLES; (e.g., VZV, HSV, coxsackievirus, poxviruses, Rickettsia akari). 2. Bullae - Staph scalded skin syndrome cause cleavage of stratum corneum and/or granulosum - toxic epidermal necrolysis cause cleavage of stratum basale (germinativum) - Bullae are also seen in necrotizing fasciitis, gas gangrene, and Vibrio vulnificus infections. 3. Crusted lesions; usually starts with a bullous phase before development of a golden-brown crust. 4. Folliculitis **Hot tub folliculitis is a diffuse condition caused by pseudomonas aeruginosa 5. Popular and nodular lesions; caused by Bartonella henselae (cat-scratch disease and bacillary angiomatosis), Treponema pallidum, human papillomavirus, mycobacteria, and helminths. 6. Ulcers with or without eschars ** Ulcerated lesions on the genitals can be caused by chancroid (painful) or syphilis (painless). 7. Erysipelas ** S. pyogenes is the exclusive cause.

Question 79

Epidermal inflammatory reactions 1. Fluid accumulation 2. Most neutrophils with serous fluids within or beneath epidermis 3. Collection of serous fluid with small amount of inflammatory cells

Answer 79

1. VESICLES; fluid accumulation (serous exudate) 2. PUSTULE; most neutrophils with serous fluids within or beneath epidermis (Purulent or suppurative exudate) 3. BULLA; collection of serous fluid and have small numbers of inflammatory cells

Question 80

Direct entry into skin by bacteria **identify structure (epidermis, dermis, hair follicles, fascia, muscle), infection and common cause - impertigo affect what skin layer? Erysipelas? Folliculitis? Gangrene? Necrotizing fasciitis? - where would you see anaerobes causing infection **which is more deadly; strep pyogenes or staph aureus

Answer 80

1. Epidermis -infection; Impetigo - cause; Strep pyogenes and/or staph aureus 2. Dermis - infection; Erysipelas - Strep pyogenes 3. Hair follicles - folliculitis, boils (furuncles), carbuncles - Staph aureus 4. Fascia - Necrotizing fasciitis - caused by ANAEROBES AND MICROAEROPHILES, usually mixed infections 5. Muscle - myonecrosis gangrene - caused by clostridium perfringes (other clostridium) **Both strep pyogenes (weak inflammatory response) and staph aureus (strong inflammatory response) cause skin infections. STREP PYOGENES is more deadly

Question 81

Skin manifestation of systemic infections **Identify organism and disease based on skin manifestation 1. “Rose spots” containing bacteria 2. Ecthyma gangrenosum 3. Erythematous rasa (toxin) 4. Rash and desquamating (toxin)

Answer 81

1. ENTERIC FEVER (rose spots); salmonella typhi and salmonella paratyphi 2. SEPTICEMIA (ecthyma gangrenosum); pseudomonas aeruginosa 3. SCARLET FEVER (erythematous rash); strep pyogenes 4. TOXIC SHOCK SYNDROME; staph aureus

Question 82

Example of inflammation **Reactivation of varicella-zoster virus infection - clinical presentation - signs of inflammation (4) - what 2 cause pain - infiltration of what cell? - wait 3 weeks for what response?

Answer 82

SHINGLES - Clinical presentation: MACULES and pustular VESICLES: - Extremely painful, redness, warm, limited edema - BRADYKININ and PGE2 sensitize the sensory nerve endings to mediate PAIN - NEUTROPHIL infiltration. - Intracellular pathogen, wait for 3 weeks to have IgG response.

Question 83

IDENTIFY CONDITION Perioral erythema covers entire body within-2 days POSITIVE NIKOLSKY’S SIGN large blister with clear fluid, no organism, no leucocytes. Circulation of the exfoliative toxins A or B, which are serine proteases, cleave desmosomal cadherins in stratum granulosum layer Pain management. Bacterimia rare

Answer 83

Staphylococcal Scalded Skin Syndrome (Ritter’s disease)

Question 84

What 3 conditions are related to hair follicle **WHAT IS typical of bacterial infections, due to the hydrolytic enzymes carried out by neutrophils (creamy yellow in color) - RISK FACTORS? - most caused by? - treatment?

Answer 84

Skin abscesses, furuncles, and carbuncles • All are related to hair follicle. • Collection of pus within the dermis and deeper skin tissues (pustule) • LIQUEFACTIVE NECROSIS necrosis, typical of bacterial infections, due to the hydrolytic enzymes carried out by neutrophils (creamy yellow in color) • Risk factors: Diabetic, immunologic abnormalities and breaches to the skin barrier. • Most are caused by infections. May be polymicrobial or monomicrobial. S. AUREUS OCCURS IN UP TO 50% cases. • Treatment: Small furuncles, warm compresses to help drainage. incision and drainage. The role of ancillary antimicrobial therapy is unclear.

Question 85

Tender, SUPERFICIAL erythematous and edematous lesions The infection spreads primarily in the upper dermis and superficial lymphatics (deeper dermis and subcutaneous fat is cellulitis) Mainly affected young and elders. Fiery red (salmon red), advancing erythema. The rash is usually confluent, and sharply demarcated from the surrounding, normal skin. **always caused by what bacteria?

Answer 85

Erysipelas **It is always caused by GAS

Question 86

Rash is intensely red, involves skin and deeper subcutaneous tissues, sharply demarcated, swollen and indurated. Localized pain, inflammation (erythema, warmth), lymph node enlargement, and systemic signs ( chills, fever, leukocytosis). The distinction between infected and non-infected area.

Answer 86

Erysipelas of the leg **always caused by GAS (Group A strep)

Question 87

• Localized staphylococcal scalded skin syndrome. • Happens in newborns and young children • Culture positive • No Nikolsky’s sign • Highly communicable **Caused by what organism that produce what toxin?

Answer 87

BULBOUS IMPETIGO - variational strain of staph aureus - happen in newborns, young children and catalase positive - NO NIKOLSKY SIGN (it is not a blistering skin condition) **Caused by S. aureus of phage group II that produces EXFOLIATIVE TOXIN A (no direct bacterial colonization) that causes loss of cell adhesion in the superficial epidermis by targeting the protein desmoglein 1

Question 88

• Papules progress to vesicles surrounded by erythema • Most frequently observed in children ages 2 to 5years. • Usually occurs in warm, humid conditions • Risk factors, poverty, crowding, poor hygiene and underlying scabies • GAS and S. aureus are most common causes **lead to what?

Answer 88

Non-bulbous impetigo Impetigo caused by nephrogenic GAS can lead to post-streptococcal glomerulonephritis **from poor hygiene ; GAS and staph aureus

Question 89

Contagious superficial infection Primarily seen in young children (2-5 yr.) Poor personal hygiene purulent with crusting A common disease of children It is commonly caused by Streptococcus pyogenes either alone or together with Staphylococcus aureus

Answer 89

Impetigo (pyoderma, impetigo contagiosa): - contagious (poor hygiene) - dry crust and scabbed (dry pus from dried neutrophils, dru monocytes)

Question 90

• Redness, induration, heat, and tenderness, the distinction between infected and noninfected area is not as clear • Often accompanied by inflammation of the draining lymph nodes. • 90% of cases are caused by GAS and S. aureus. • In unimmunized children, infection with h. influenzae type B. • Cellulitis associated with bites or scratches from cats or dogs (P. multocida). • All develop rapidly (24 to 48 hrs) from minor injury to severe septicemia. • Elevation of the affected area and empiric antibiotic therapy. 2. What can occur in elbow of cancer patient who previously had bacteremia

Answer 90

Cellulitis: Acute Inflammation 90% caused by GAS or staph aureus 2. Staph aureus Cellulitis

Question 91

an ulcerative form of impetigo in which the lesions extend through the epidermis and deep into the dermis

Answer 91

Ecthyma Ecthyma gangrenosa from P. aeruginosa bacteremia in neutropenic patients

Question 92

What is associated with use of TAMPONS - caused by what toxin? - activated Tc Ella release what?

Answer 92

Toxic shock syndrome (TSS): cutaneous and soft tissue involvement, and initially associated with use of tampons. TSS is caused by toxic shock syndrome toxin-1 (TSST-1), and is a superantigen. But other enterotoxins may be involved too. Activated T cells then release IL-1, IL-2, TNF-alpha and TNF-beta, and IFN-gamma in large amounts, resulting in the signs and symptoms of TSS. IL-1 is an endogenous pyrogen and thus causes the high fevers associated with TSS.

Question 93

3 types of gangrene (form of coagulation necrosis) 1. a form of coagulative necrosis (gangrenous necrosis) that develops in ischemic tissue, where the blood supply is inadequate to keep tissue viable. It is characteristics ischemia of lower limb (diabetics), 2. characterized by thriving bacteria and has a poor prognosis (compared to dry gangrene) due to sepsis resulting from the free communication between infected fluid and circulatory fluid. It is similar to liquefactive necrosis 3. is a bacterial infection that produces gas within tissues.

Answer 93

1. Dry gangrene; mainly due to ischemia. Cut off blood vessel. **E.g DIABETIC FEET (no infection) 2. Wet/infected gangrene; gangrene + infection 3. Gas gangrene

Question 94

Identify condition AND THE 2 TYPES - deep seated infection of the subcutaneous tissue leading to destruction of fascia and fat, but may spare skin - Common features: extensive tissue destruction, thrombosis of blood vessels, bacteria spreading along fascial planes, and unimpressive infiltration of inflammatory cells

Answer 94

1. Type I necrotizing fasciitis - a mixed infection caused by aerobic and anaerobic bacteria and occurs most commonly after surgical procedures and in patients with diabetes and peripheral vascular disease. 2. Type II necrotizing fasciitis - is a mono-microbial infection caused by group A streptococcus (GAS, Streptococcus pyogenes). Necrotizing fasciitis caused by community-associated methicillin-resistant Staphylococcus aureus (MRSA) as a monomicrobial infection has also been described. **Both wet gangrene

Question 95

• Rapidly progressive wound infections after exposure to contaminated seawater • The wound infections are characterized by initial swelling, erythema, and pain followed by the development of vesicles or bullae and eventual tissue necrosis. • Mortality: 50%

Answer 95

Necrotizing fasciitis caused by V. vulnificus

Question 96

• Most often due to C. perfringens, , C. septicum, C. histolyticum or C. sordellii • Usually associated with local trauma • Gas is always found in the skin, but fascia and deep muscle spared. • Nonclostridial cellulitis is due to infection with a mixed anaerobic and aerobic organisms that produce gas. Associated with diabetes with a foul odor. • Myonecrosis is found in 50% of patients with necrotizing fasciitis caused by GAS

Answer 96

Necrotizing infection of muscle: myonecrosis

Question 97

• Gram positive and spore forming (grow overnight and form spore in stationary phase with no nutrient) **Identify toxins **Environmental infection

Answer 97

BACILLUS ANTHRACIS - Capsule (D glutamic acid): - Exotoxin with three parts: ∙ a-Edema factor (EF) ∙ b-Lethal factor (LF) ∙ c-Protective antigen (PA) ** ANTHRAX is a disease of herbivores. Animals are vaccinated in the USA. Spores can survive decades in soil and on animal skins. Spores are traumatically implanted, inhaled or ingested.

Question 98

IDENTIFY known virulent factors of bacillus anthracis **edema vs lethal toxin - protective antigen?

Answer 98

• Typical A-B type binary toxin: – Edema factor +Protective antigen=edema toxin – Lethal factor + Protective antigen=lethal toxin ● Edema factor (cya): A portion of the edema toxin, adenylate cyclase, similar to the one produced by Bordetella pertussis, activated by human calmodulin, resulting in increased intracellular cAMP-impaired flow of ions and water. ● Lethal factor (lef): A portion of the lethal toxin, a protease, induces macrophage to produce high levels of cytokines that trigger the shock. ● Protective antigen (pag) : B portion of the A-B toxin that promotes entry of EF into phagocytic cells

Question 99

1. Identify - most common form of bacillus anthracis - Painless papule at the site of inoculation - Progress to an ulcer surrounding vesicles - Necrotic eschar 2. Very rare form of anthrax 3. What is Woolsorter’s disease?

Answer 99

1. Cutaneous Anthrax - Germination, rapid proliferation ,toxin release and localized tissue necrosis - Round black lesion with a rim of edema: malignant pustule 2. GI anthrax; rare - Rare. Spores in contaminated meat → GI ulcers + edema. Nausea, fever, abdominal pain, vomiting blood, and diarrhea. 3. Inhalation anthrax (woolsorter’s disease); asymptomatic before it causes bacteremia in blood stream Spores inhaled into lungs → macrophages → lymph nodes germinate and kill macrophages. Exotoxin → lymph node hemorrhage and edema, hemorrhagic mediastinitis, pulmonary edema, and hemorrhagic pleural effusions. A widened mediastinum is a critical diagnostic feature. Bacteria → bloodstream → septicemia and death.

Question 100

1. How do you diagnose B. Anthracis 2. What is protection and therapy for B. Anthracis

Answer 100

1. • Microscopic examination of material from papules. No spores in clinical specimen, serpentine chain of bacilli - Culture: Non-hemolytic, sticky, colonies - Biochemical tests ultimately should confirm presumptive diagnosis. 2. - Inactivated cell-free product as vaccine against PA-short term. Live attenuated vaccine is also available. - Treatment should last for 60 days with: Penicillin, Ciprofloxacin, Doxycycline

Question 101

1. Drugs as antigens 2. What is most common allergic reaction

Answer 101

1. • Molecular mass >10,000 (most drugs <1,000 daltons) - Hapten/Carrier complex to stimulate the immune system; covalent binding required. ** Hapten: substance that can react with a specific antibody - Molecular weight too low for it to be immunogenic by itself **Carrier: substance with immunogenic potential **Carrier + Hapten = Immunogenic compound 2. DERMATOLOGIC REACTIONS (rash) is most common allergic reaction **If this happens, stop the medication

Question 102

Gell and Coombs classification **identify different classifications and onset (4)

Answer 102

1. I, II, III, IV Classifications - type I; anaphylactic (IgE mediated) - onset is <30minutes - type II; cytotoxic antibodies - onset is 5-12 hrs - type III; immune complex - onset is 3-8 hrs - type IV; cell mediated (delayed) - onset is 24-48 hrs 2. Typical Onset varies

Question 103

Manifestations of drug allergies (3)

Answer 103

1. Anaphylaxis – life threatening w/ multiple organs involved (respiratory, cardiovascular, Skin, GI) 2. Serum Sickness (fever, malaise, lymphadenopathy) - Soluble circulating immune complexes form under excess antigen - Cephalosporins: Cefaclor and Antivenins 3. Drug Fever - Infection vs Inflammation vs Drug Reaction - Highly variable on presentation

Question 104

Drug induced autoimmunity (4)

Answer 104

1. Systemic Lupus Erythematosus 2. Hemolytic Anemia 3. Renal Interstitial Nephritis 4. Hepatic hypersensitivity

Question 105

Identify condition (drug allergy) - Inflammation and necrosis of blood vessels - Usually the skin but may also involve multiple organs

Answer 105

Vasculitis

Question 106

Dermatological drug allergies (8)

Answer 106

1. Erythematous/maculopapular rash (most common) 2. Urticaria 3. Fixed Drug Eruptions 4. Phototoxicity 5. Eczematous Contact Dermatitis 6. Erythema Multiforme 7. Stevens Johnson Syndrome (SJS) 8. Toxic Epidermal Necrolysis (TENs)

Question 107

Pulmonary reactions (drug interactions)

Answer 107

1. Rhinitis/Asthma 2. Acute infiltrate/Chronic fibrotic pulmonary reaction (Nitrofurantoin)

Question 108

Hematologic reactions (drug allergies)

Answer 108

1. Eosinophilia 2. Bone marrow aplasia (Aplastic anemia) - Chloramphenicol 3. Hemolytic Anemia 4. Thrombocytopenia 5. Granulocytopenia (Agranulocytosis)

Question 109

Management of drug allergies (6) **Enter allergic reaction where? **Report ADR to? **what is naranjo scale?

Answer 109

1. Document in Patient Chart!! (FDA when necessary) 2. Discontinuation of the agent when possible. 3. Symptomatic/supportive care of signs and symptoms 4. Substitution, if necessary, of another drug or agent. 5. Desensitization protocols available - No other options to treat 6. Skin testing for drug allergy - If questionable documented allergy - Allergy testing in general **Enter Allergic Reaction into Patient’s Chart; Avoid related mistake in the future, Protect patients from re-exposure, Protect life threatening problems **Report ADR to FDA; Medwatch Program to collect Phase IV info **Naranjo Scale - Probability of allergic rxn is related to the medication in question - Definite, Probable, Possible, & Doubtful

Question 110

Identify risk factors of having a drug allergy (4)

Answer 110

1. Chemical structure - Similar structures may cause cross sensitivity 2. Molecular weight - High molecular weight increases chance - Low molecular weight must form hapten/carrier 3. Route of administration - Parenteral vs. topical 4. Dose, duration of therapy, repeated exposure to drug - Reaction may present on repeat exposures **Watch for Eosinophilia (NAACP)

Question 111

Identify manifestation of drug allergy A. Acute, life-threatening allergic reaction - Often involves multiple organ systems B. Presentation - Skin - pruritis, urticaria, erythema, and angioedema - GI tract - nausea, vomiting, abdominal pain, and diarrhea - Respiratory tract - chest tightness, stridor, and bronchospasm - Cardiovascular - hypotension, tachycardia, and dysrhythmias C. Onset - 30-120 minutes following exposure **Identify fatal complications? (Cause?)

Answer 111

Anaphylaxis ** Fatal anaphylaxis; Asphyxia due to laryngeal edema or cardiovascular collapse

Question 112

Identify manifestation of drug allergy - Syndrome resulting from soluble circulating immune complexes that form under conditions of antigen excess - Presentation **Most common: FEVER, MALAISE, and LYMPHADENOPATHY** Other: arthralgia, urticaria, and morbilliform skin eruptions ***IDENTIFY onset and common agents (2)

Answer 112

Serum sickness Onset: 7-14 days following exposure Common agents: Cephalosporins, antivenim (equine serum leads to allergic reaction)

Question 113

Identify manifestation A. Infection vs. Inflammation process vs. Drug Reaction B. CNS – Alters temperature regulation or stimulate the release of endogenous pyrogens from WBCs (i.e. interleukin-1 and tissue necrosis factor) C. Direct pharmacologic effects on tissues; Chemotherapy - Tumor cell destruction - Fever D. Onset: 7-10 days **Identify - temperature pattern - resolution? - common agents? (2)

Answer 113

Drug fever E. Temperature pattern of drug fever is highly variable - Low grade and continuous - vs - spiking and intermittent - May run as high as 104-105 degrees F. F. Prompt resolution usually follows after removal of causative drug - Fever will recur with re-administration G. Common agents: Amphotericin B, Antimicrobials

Question 114

Identify manifestation of drug allergy S&S; RIGORS, FEVER AND HYPOTENSION - Typically follow antibiotic treatment for a number of spirochetal and bacterial infections - Thought to be related to the sudden release of bacterial components from injured and/or killed bacteria **Common agents; TCN, doxycycline, Pen G A. Classic cases are after treatment of what? (2) - tx of above 2 B. Other causes? C. Also observed from what tx?

Answer 114

Jarisch-Herxheimer Reaction (JHR) A. Classic cases of JHR (~75-85% of the time) are after treatment of - Louse Borne Relapsing Fever (LBRF) or Tick Borne Refractory Fever (TBRF) - Usually within hours of the antibiotic administrationi) Tx of LBRF is Tetracycline, Doxycycline, or Pen G Procaine II) Tx of TBRF is Tetracycline, Doxycycline, Pen G, Erythromycin, or Ceftriaxone B. Other tradition causes of JHR have been described following treatment for secondary and tertiary SYPHILIS, BRUCELLOSIS, and ENTERIC FEVER. It can also occur with treatment of SCHISTOSOMIASIS and TRYPANOSOMIASIS. C. Also been observed following treatment of BORELLIOSIS, particularly Borrelia recurrentis, with a mortality rate of ~5%

Question 115

Drug induced autoimmunity - occur in Drugs with a hydrazine or amino group linked to an aromatic ring; Procainamide, Hydralazine, Isoniazide, Phenytoin - MANIFESTATIONS: **Most common: fever, malaise, rash, arthralgias and myalgias **Others: mucosal ulcers, pulmonary involvement Identify - onset (how long after taking drug will you observe this?) - is it more common in male vs female? - timeline for it to resolve? - common agents

Answer 115

SLE - SYSTEMIC LUPUS ERYTHEMATOSUS ** fever, malaise, rash (look like ring worm), arthralgias and myalgias - Onset: Several months after beginning drug - Sex distribution EQUAL with drug induced SLE - Usually resolves 3-6 months after discontinuation *Symptoms may persist - Common Agents: Procainamide, hydralazine, isoniazid, phenytoin, quinidine, penicillamine

Question 116

Drug induced autoimmunity A. Manifestations: - FEVER, RASH, and EOSINOPHILIA - Proteinuria, hematuria, and eosinophiluria B. Two possible mechanisms: - Humoral; Antibody-mediated mechanism - antibodies to a drug-basement membrane complex - Cell-mediated immune mechanism. C. Common agents: Antistaphylococal penicillins (methicillin, ox, clox, diclox, nafcillin), Cimetidine, Sulfonamides

Answer 116

INTERSTITIAL NEPHRITIS **3 classic presentation - fever, rash and eosinophilia

Question 117

Drug induced autoimmunity Not very common. Watch LFTs frequently Fever, rash, eosinophilia and granulomas on biopsy **Identify common agents (2)

Answer 117

Hepatic Hypersensitivity Reaction/Toxic Hepatitis - Drug or its metabolite may not be inherently toxic to the liver - Drug or metabolite acts as a hapten to induce an autoimmune reaction - Manifestation: Eosinophilia, fever, rash, and granulomas on biopsy - Common Agents: Erythromycin, penicillins

Question 118

Identify drug allergy A. Characterized by inflammation and necrosis of blood vessels B. Usually limited to skin; Can involve multiple organs C. Manifestations - Most common: Palpable purpuric lesions - Papules, nodules, ulcerations, or vesiculobullous lesions - Usually lower extremities, possbily upper limbs

Answer 118

Vasculitis - Sand paper appearance on patient skin - Mostly lower extremities but can be upper extremities too - Looks like vascular hemorrhaging but it got a texture to it

Question 119

**Dermatologic reactions 1. Most significant dermatologic reactions (2) 2. Which 3 are like a stage 3 burn 3. Most common? 4. Least common?

Answer 119

1. Most significant (2) - Stevens-Johnson Syndrome - Toxic Epidermal Necrolysis 2. More like stage 3 burn - Erythema Multiforme - Stevens-Johnson Syndrome - Toxic Epidermal Necrolysis 3. Most common (5) - Pruritis - Maculopapular rashes - Urticaria/Angioedema - Fixed drug reactions - Phototoxic 4. Less common (2) - Toxic epidermal necrolysis (TENs) - Stevens-Johnson Syndrome (SJS)

Question 120

Identify dermatologic reaction (drug allergy) A. Symmetrical, flat red rash; Small confluent bumps B. Begins on the extremities in ambulatory patients or on the back of bedridden patients C. Palms and soles - spared D. Onset: - Early (2-3 days) in previously sensitized - Late (>9 days) E. Common Agents; Penicillins, antibiotics, anticonvulsants

Answer 120

Maculopapular/Morbilliform Rash - Starts in back or trunk and it is very diffuse

Question 121

Identify the dermatologic reaction (drug allergy) Onset; Minutes/hours or can be after several days Common Agents; Antibiotics, NSAIDs, Anticonvulsants **2 conditions - 2 signs you see from Ace inhibitor S.E (locations?)

Answer 121

Urticaria/Angioedema A. URTICARIA = Hives/Wheals (looks like something is raised up) - Blood plasma leaking out of small blood vessels - Caused by histamine release - Mast cells in dermis **Dermatographism; skin is raised when you try to write on it B. Pruritic, edematous wheals with surrounding erythema C. ANGIOEDEMA (phenytoin) - facial and periorbital - Angioedema and cough major side effects with Ace inhibitor - Anything after exposure (not just from increased dosage) - Mouths and lips is very common (where you would grow a goatee)

Question 122

Fixed drug eruptions 1. What type of lesions? 2. Common agents?

Answer 122

1. Single or multiple edematous, pigmented lesion - Frequently dark red, violet, or brownish-pink - Reappear in the same location when drug reinitiated 2. Common Agents - Antibiotics: PCN, TCN, Cipro, Bactrim - NSAIDs, Quinidine, Sulfonamides

Question 123

Phototoxicity vs photoallergy - which is mainly from sun? - which is combination of hapten (chemical reaction) and sun?

Answer 123

1. Phototoxicity (doxycycline) - Immediately after drug treatment after a short EXPOSURE TO SUNLIGHT (Sunburn) - UV light results in drug emitting energy that can damage tissue 2. Photoallergy (ketoprofen) - Activated by long wavelength SUNLIGHT - Erythema/edema progress to one of the following (3); urticarial, eczematous papulovesicular, or exudative eruptions - UV light + drug or metabolite = hapten - HAPTEN + tissue antigen = complete antigen **Common Agents: TCNs, Carbamazepine, Griseofulvin, Coal Tar derivatives, Oral Contraceptives

Question 124

Identify dermatological reaction (drug allergy) - New rash develops - Normally during topical treatment of a preexisting dermatosis - The new rash becomes erythematous, indurated, and vesicular

Answer 124

Eczematous Contact Dermatitis **Zinc ointment

Question 125

*Identify dermatological reaction (drug allergy) - Begins as a round, small, erythematous macule - Edematous and papular over time - Hallmark characteristic; Concentric (target) lesions - Hands, feet, limbs, mucous membranes, and face - Often preceded by mild upper respiratory symptoms - Common Agents: Antibiotics, Anticonvulsants, NSAIDs

Answer 125

ERYTHEMA MULTIFORME (aspirin) - Hands, feet, limbs, mucous membranes, and face ** **targeted bull’s eye - lead to Steven Johnson

Question 126

*Identify dermatologic reaction (drug allergy) A. Severe variant of erythema multiforme - Mucosal and conjunctival edema - High fever - Myalgias, arthralgias - Skin lesions may be severe with large bullae B. Complications: - Keratitis - Conjunctival scarring - Blindness C. Common Agents: Sulfas, Anticonvulsants, NSAIDs

Answer 126

Stevens Johnson Syndrome (SULFA) - difficult to treat (skin Barrier sloughing off) - start from head and go system wide - mucosal involvement - ocular involvement **Sulfa

Question 127

*Identify dermatologic reaction (drug allergy) - Begins with malaise and fever - Erythematous rash appears; Progresses to large flaccid bullae - Bullae become confluent, epidermis sloughs in large sheets, leaving exposed raw dermis (equivalent to a second degree burn) - Mortality 3% within first 3-4 days; Fluid and electrolyte imbalance, sepsis - Common Agents: Antibiotics, Anticonvulsants, NSAIDs

Answer 127

Toxic Epidermal Necrolysis - high mortality - skin sloughing (replace fluids and electrolytes)

Question 128

2 pulmonary reactions of drug allergy

Answer 128

1. Rhinitis/Asthma - Possibly IgE-mediated allergy from agents that can cause anaphylaxis - NSAIDs, Sulfites 2. Acute infiltrative and chronic fibrotic pulmonary reaction - cough and dyspnea - Debate whether these reactions are allergic in nature or not - Nitrofurantoin, Bleomycin

Question 129

Hemolytic reaction (drug allergy) - Sometimes the only evidence of drug allergy; but not enough reason to terminate therapy of drug all together - Common Agents; Antibiotics, Digitalis

Answer 129

EOSINOPHILIA

Question 130

Hematologic reaction (drug allergy) A. Pancytopenia- common characteristics - WBC < 3,500/mm3 - PLT < 55,000/mm3, - Hgb < 10 gm/dl with a Reticulocyte count of < 30,000/mm3 B. Signs/symptoms - Fatigue, weakness, stomatitis, easy bruising, pettechiae C. Onset - Avg=6.5 weeks after initiation of offending agent - May appear after the drug has been discontinued **WHAT DRUGS CAUSE THIS? - how does this happen? - common agents?

Answer 130

APLASTIC ANEMIA - Dose Dependent (Chemotherapy) - Idiosyncratic (Chloramphenicol) - Drug or drug metabolite binds cell; IgG antibodies attack cell-drug conjugate leading to destruction of cell by complement ***(Drug + Cell) - IgG antibiodies attack - Common agents: Antibiotics, Anticonvulsants, NSAIDs

Question 131

Hematologic reactions (drug allergy) A. Drug/Drug metabolite binds ERYTHROCYTES - IgG antibodies attack - destruction by complement - Penicillins, cephalosporins B. Immune complexes (drug + antibody) form in the serum - Adsorb to the erythrocyte surface - destruction by complement - Innocent bystander - Quinidine C. IgG-antidrug metabolite ANTIBODY binds ERYTHROCYTE membrane; antibody coated cells phagocytized - Coombs positive - Methyldopa, penicillin

Answer 131

HEMOLYTIC ANEMIA

Question 132

Hemologic reactions (drug allergy) A. Drug/drug metabolite binds platelet; Heparin B. Innocent bystander; Quinidine, Antibiotics C. Drug + HLA antigens - HLA antigens - found on platelets; Help body recognize self vs. non-self - Drug-platelet combination is then recognized as non-self resulting in destruction by AUTOANTIBODIES - Gold Salts D. Pettecchia, blisters in mouth – risk of bleed higher; intervention must occur

Answer 132

THROMBOCYTOPENIA

Question 133

Hematologic reactions (drug allergy) - Chills, fever, sore throat - Mechanisms; Similar to thrombocytopenia

Answer 133

Agranulocytosis

Question 134

Immune-mediated, hypersensitivity reaction resulting in epidermal cell injury • Epidermal cells are attacked by CD8+ cytotoxic T-cells; target Ag unknown • Erythematous macules and papules, vesicles and bullae (multiforme) on extremities that are strikingly symmetric. Target lesions are often diagnostic. • Lesions may become pruritic and painful **triggers? (4) **most common causes of reoccurring erythema multiforme (2)? - most infectious causes

Answer 134

Erythema multiforme Triggers – idiopathic, medications, HSV infection, mycoplasma pneumonia • Meds include sulfa drugs, penicillin, phenytoin, allopurinol, barbiturates. • Erythema multiforme from HSV can recur, can use acyclovir as prophylaxis or at first sign of HSV infection for recurrent erythema multiforme • Usually self-limited **HSV infection and Mycoplasma pneumonia are the 2 most infectious causes of reoccurring erythema multiforme

Question 135

Histology of erythema multiorme **Early vs Later ?

Answer 135

1. Early: superficial perivascular, lymphochytic infiltrate, DERMAL EDEMA, accumulation of lymphocytes along dermoepidermal junction associated with DEGENERATING and NECROTIC KERATINOCYTES 2. Later: LYMPHOCYTES migrate into epidermis, EPIDERMAL NECROSIS occurs with blister formation. Target lesion has central necrosis surrounded by perivenular inflammation **lymphocytes attack keratinocytes - red and dead

Question 136

• More severe than erythema multiforme • Children > adults • More extensive involvement of mucous membranes including mouth and conjunctivae. • Systemic manifestations may include fever, difficulty eating, renal failure, and sepsis. • Causes are usually sulfa drugs and anticonvulsants. **treatment

Answer 136

Stevens-Johnson Syndrome **more extensive INVOLVEMENT of the MUCOUS MEMBRANES (ORAL) • Treatment is mostly supportive. • Stop any causative medications. • May need to treat in burn unit. Maintain hydration, prevent secondary infection, provide pain relief. • Mortality may be as high as 15%.

Question 137

• More severe than Stevens-Johnson. • Dermatologic emergency. • Detachment of large areas of epidermis. • Mortality rate is 30%. • Treatment is the same as Stevens-Johnson: Stop medication and treat in burn unit.

Answer 137

Toxic Epidermal Necrolysis **skin sloughed off ** The necrotic epidermis is lifting off the dermis to form a subepidermal bulla.

Question 138

EM vs Steven Johnson vs TEN - body surface involvement - morphology of lesions

Answer 138

1. EM Body involvement; <10% - Macules to papules, vesicles to bullae, typical target lesions 2. Steven Johnson - 10-30% body involvement - Generalized form of EM Involves mucous membranes 3. TEN - >30% body involvement - Detachment of large epidermal sheets w/ or w/o target lesions/widespread macules

Question 139

Subacute spongiotic dermatitis. • Not contagious but possibly related to human herpes virus type 7. • Affects older children and young adults. • Most common in winter. 1. Presentation 2. Common in what body areas? Tx? Not found in what part of body? 3. Histology

Answer 139

Pityriasis Rosea A. Presentation; Get initial “herald patch” that resembles ringworm. • Progresses to generalized oval, slightly elevated, scaling papules that resemble the herald patch but are smaller. • The lesions are pink with scaling near the border. • Described as classically having a “CHRISTMAS TREE” PATTERN. • The patient feels well. B. Common on trunk, upper arms, and thighs. Usually not found on the face ** • Pruritis often present and varies in severity. • Spontaneously remits in 6 - 8wks w/o treatment. Recurrence is rare. • Treat itching with antihistamines. C. Histology; Spongiotic dermatitis with mounds of parakeratosis and RBC extravasation

Question 140

Cause of spongioum dermatitis - Disease of middle age and older adults - Starts as edema and hyperpigmentation and leads to pruritic erythema and stasis dermatitis. *treatment

Answer 140

Venous insufficiency • Venous incompetence causes increased hydrostatic pressure and capillary damage leading to extravasation of RBCs and serum. • Incompetent venous valves in lower leg • Dependent edema • Stasis dermatitis – Scaling, inflammation, pruritis, hyperpigmentation • Ulceration above medial malleolus Treatment - Avoid trauma to the area - Compression stockings - Topical steroids for stasis dermatitis - Wound care for ulcers – debridement and Unna boot

Question 141

Histology of stasis dermatitis

Answer 141

• This is a mild chronic spongiotic dermatitis • Superficial aggregated vessels with erythrocyte extravasation causes hemosiderin to collect which gives skin a thickened, rough, brown appearance

Question 142

• Accelerated proliferation of skin cells resulting in scaling. • Chronic condition with exacerbations and remissions. • Can occur at any age, average is 35 years. • Pathogenesis: Genetic and environmental; 1/3 have family history. • Impact on quality of life and self-esteem can be enormous. **presentation - what sign? Common where?

Answer 142

Psoriasis - increased proliferation - Process is normally 28 days for keratinocytes to move from stratum basale to shedding. In psoriasis, the process is 3-4 days. • Well-demarcated, erythematous plaques and papules with silver scaling • Auspitz’s sign**: pinpoint bleeding on removal of scale • Symmetrical: – Elbows, knees, buttocks, SCALP, gluteal cleft, trunk, face (common in scalp) • Trauma to the skin and stress can cause exacerbations. (Koebner phenomenon)

Question 143

1. Histology of psoriasis 2. Other less common types (3) - which involve entire body - which follow strep infection - which involve pustules

Answer 143

1. Psoriasis vulgaris • Downward elongation of rete ridges • Thinning of overlying stratum granulosum with parakeratosis above • Aggregates of neutrophils with minimal surrounding spongiosis • Capillaries in dermal papillae are brought close to the surface 2. Less common types – Erythrodermic – involves entire skin, very serious (entire body is red) – Guttate – scattered, drop-like, pink, scaly plaques. May follow strep infection. – Pustular – pustules on erythematous skin, can be on palms/soles only or generalized.

Question 144

1. Effect of psoriasis on the nails 2. Arthritis?

Answer 144

1. Nails • 50% of patients have nail involvement • Oil Spotting – Focal brown discoloration of nail plate • Onycholysis – Distal separation of plate from bed • Subungual hyperkeratosis • Pitting 2. Arthritis 5% develop psoriatic arthritis. • Most is mild with asymmetric small and medium joint involvement. • Arthritis mutilans, is a very destructive form of psoriatic arthritis with significant periarticular bone resorption. • Erosions cause a “pencil in cup” deformity where one articular surface is eroded creating a pointed appearance. Articulating bone is concave, resembling an upside down cup

Question 145

• Aka “cradle cap” and dandruff • Chronic inflammatory process affecting areas rich in sebaceous glands • Peaks in infancy and adulthood • Thought to be associated pathologically with the yeast Malassezia furfur which is normal flora on skin A. Location? B. Presentation C. Histology D. Treatment

Answer 145

Seborrheic dermatitis **Atypical and severe with HIV. Also seen in Parkinson’s A • Usually on – Scalp – Ears – Eyebrows – Nasolabial folds – Chest • Usually symmetrical in distribution B. • More common in Parkinson and HIV! • Mild cases manifest as dandruff. • Yellow, greasy, scaly patches with surrounding erythema. • Asymptomatic, but may be itchy. • In babies, condition will remit after 6-8 months. The course is chronic in adults. C. Features of both spongiotic dermatitis (early) and psoriasis (later) • Mounds of parakeratosis with neutrophils and serum at the ostia of hair follicles • Perivascular infiltrate of lymphocytes • Etiology: unknown D. Treatment: Dandruff shampoo (selenium sulfide) Mild topical steroids for more severe cases

Question 146

• Idiopathic inflammatory disorder • 5 P ’s : “ Pruritic, Purple, Polygonal, Planar papules, Plaques” • Uncommon but not rare (5/1000) A. Presentation B. Associated with what viral infection? C. Histology D. Diagnosis

Answer 146

Lichen plants **Associated with HEPATITIS C A. • History: severe itching • Most common on wrists and ankles • Wickham’s striae – fine, reticulated, white lines • Mucous membrane involvement is common • Koebner phenomenon (trauma to the skin and stress can cause exacerbations) B. • May also be associated with Hepatitis C C. Histology - Interface dermatitis – dense, continuous infiltrate of lymphocytes along the dermoepidermal junction • Associated with degeneration and necrosis of basal keratinocytes • Civatte bodies – incorporation of necrotic basal keratinocytes into inflamed papillary dermis • Dermoepidermal interface changed to a more angulated zigzag pattern (saw-toothing) D. Diagnosis Interface dermatitis – dense, continuous infiltrate of lymphocytes along the dermoepidermal junction • Associated with degeneration and necrosis of basal keratinocytes • Civatte bodies – incorporation of necrotic basal keratinocytes into inflamed papillary dermis • Dermoepidermal interface changed to a more angulated zigzag pattern (saw-toothing)

Question 147

• MULTISYSTEM** autoimmune disease involving connective tissues and blood vessels • Incidence is 40-200/100,000 • More common in African Americans • Female to male ratio is 9:1 • Age of onset is 30-40 • History: 36% have skin lesions. Sunlight exacerbates rash. Skin lesions may burn or itch. • Also present with fatigue, fever, weight loss, malaise, arthralgias, CNS symptoms. A> presentation B. Due to what? False positive where? Survival rate? Treatment? C. Histology

Answer 147

Systemic Lupus Erythematosus A. Presentation; malar rash, spares basolateral folds • Malar rash – “butterfly rash” erythematous, confluent, macular eruption with clear borders • Multisystem involvement – oral ulcers, renal disease, pericarditis, pneumonitis, peritonitis, hepatosplenomegaly, myopathy, neuropathy, lymphadenopathy, seizures B. • All due to immune complex deposition • False positive on RPR and VDRL • Five year survival is 93% • Treatment – Oral steroids and immunosuppressants (methotrexate and azathioprine, etc) C. Histology • Lichenoid interface dermatitis • Epidermal atrophy • Thickening of basal membrane • Increased mucin

Question 148

BLISTERING DISEASES - 3 inflammatory - 2 non inflammatory

Answer 148

1. Inflammatory blistering disease - Pemphigus - Bullous pemphigoid - dermatitis herpetiforms 2. Non-inflammatory blistering disease - epidermolysis bullosa - porphyria cutaneous tarda

Question 149

Identify type of pemphigus (inflammatory blistering disease) - Most severe type, affects pts b/t 30-50 y/o - Involves scalp, face, axillae, groin, trunk, pressure points, and oral ulcers (a) ~90% begin w/ oral ulcers - 5-15% mortality A. Causes B. Presentation C. Histology D. Diagnosis and treatment

Answer 149

PEMPHIGUS VULGARIS A. Due to IgG autoantibodies against desmogleins 1 and 3 in desmosomes in suprabasal deep epidermis and mucosal epithelium B. - General involvement w/ flaccid blisters → rupture → crusty erosions - Postive Nikolsky sign: pressure on blister → lateral spread of lesion C. Histo: - acantholysis (lysis of squamous intercellular adhesions); - row of tombstones (single layer of intact basal cells forms blister base); - superficial lymphocytic infiltrate in dermis (can include eosinophils) - Net-like pattern of intercellular IgG deposits D. - Direct Immunofluorescence: Net-like pattern of intercellular IgG deposits - Treatment: Immunosuppressives and supportive

Question 150

Identify blistering disease • Elderly individuals • Inner aspects of thighs, flexor surfaces of forearms, axillae, groin and lower abdomen • Oral lesions in 10-15%, usually after cutaneous lesions • Ta r g e t Ags: BPAg1 & BPAg2 in the hemidesmosome • Subepidermal, nonacantholytic blisters • Sturdy blisters (roof is full thickness of epidermis), usually ~2 cm but up to 4 – 8 cm, do not rupture as easily as pemphigus, without infection will heal without scarring A. Cause B. Histology

Answer 150

Bullous Pemphigoid A. In bullous pemphigoid, autoantibodies bind BPAg1 and BPAG2, components of the hemidesomes (basal cell-basement membrane attachment plaque), leading to blister formation at the level of the lamina lucida of the basement membrane. B. Histology • Subepidermal, nonacantholytic blisters • Early perivascular infiltrate of lymphocytes • Eosinophils typically present along basement membraned and in blister cavity • Direct immunofluorescence shows linear deposition of C3 and IgG along dermoepidermal junction

Question 151

Pemphigus vulgaris vs Bullous pemphigois Age Target Ag Blister (bulla) Oral mucosa

Answer 151

1. Pemphigus vulgaris A. 30 – 50 years B. Desmoglein 3, in desmosomes C. Suprabasal, ancantholytic, +Nikolsky sign D. 80-90%, early lesions 2. Bullous Pemphigoid A. Elderly B. BPAg1 and BPAg2 in hemidesmosomes C. Subepidermal, nonacantholytic, sturdy D. 10-15% after cutaneous lesions

Question 152

• Incidence: as high as 39/100,000 • Onset is 20-60 years with 2:1 M:F ratio • Etiology: IgA autoantibodies to transglutaminases in the gut bind to those in the skin • Associated with HLA-B8, HLA-DR, HLA-DQ A. Presentation B. S&S C. Histology D. Diagnosis and Treatment

Answer 152

Dermatitis Herpetiformis A. • Symmetrically grouped lesions (herpetiformis) • Papules and plaques progressing to vesicles and bullae • Buttocks elbows knees scapular areas • Very pruritic B. Gluten sensitive enteropathy occurs in nearly all patients and must be demonstrated by small bowel biopsy. • THERE MAY BE NO GI SYMPTOMS C. Neutrophilic microabscesses in dermal papillae - Subepidermal blister *** • Neutrophil microabscesses and fibrin deposition in tips of dermal papillae • Basal cells overlying tips show dermoepidermal separation eventually coalescing to form blister • Direct immunofluorescence demonstrates discontinuous granular deposition if IgA in tips of dermal papillae **Granuar IgA deposited in papillae tips D. Diagnosis; 1. Skin biopsy 2. Antiendomysial antibodies (specific for TG) 3. Endoscopy-blunting of villi in small bowel Treatment; • Gluten-free diet – response is very slow • Dapsone – response within hours, check G6PD level, monitor methemoglobin and CBC levels • A chronic disease, 1/3 pts may have spontaneous remission

Question 153

Noninflammatory blister • Group of disorders caused by inherited defects in proteins that lend stability to the skin • At least ten genes have been implicated • Common to all is tendency to form blisters at points of pressure, rubbing, trauma • Symptoms at or soon after birth A. 3 types B. Presentation

Answer 153

Epidermolysis Bullosa A. • Simplex type – mutations in either gene encoding keratin 14 or 5 which form a functional keratin fiber resulting in a basal cell layer defects • Junctional type – blisters formed from separation lamina lucida • Dystrophic types – blisters below lamina densa, from defect in collagen VII, scar formation on healing B. • Fibrin deposition in the floor of the blister cavity • Most are pauci-inflammatory • Some cases may show neutrophils within the papillary dermis, while other cases are histologically indistinguishable from bullous pemphigoid • Dermal fibrosis (scar) may be present in the dermis

Question 154

Identify non inflammatory blister 30-50 yrs, females on OCPs, alcohol use, associated with Hepatitis C • Uroporphyrinogen decarboxylase (UROD) deficiency excessive accumulation of porphyrins • Type I (acquired disease) by exposure to drugs/chemicals, hepatic UROD is inhibited • Type II - autosomal dominant, UROD deficient in RBCs and fibroblasts A. Presentation B. Diagnosis C. Histology

Answer 154

Porphyria Cutanea Tarda A. • Porphyrins make skin photosensitive • Tense subepidermal bulla on normal appearing skin in sun exposed areas • May also get hypertrichosis on face • Exacerbated by iron, alcohol, smoking, estrogens, hepatitis C, HIV, halogenated hydrocarbons B. • Diagnosis – test for ↑uroporphyrin in urine, will fluoresce orange under Wood’s lamp C. • Subepidermal vesiculation • Acral skin with compact orthokeratosis • Solar elastosis (due to patient age and characteristic acral location) • Minimal inflammatory infiltrate • Protuberance of rigid dermal papillae into blister cavity (“festooning”) • Thickening of walls of superficial dermal vessels

Question 155

Disorder of epidermal appendages • May begin as early as 9-11 years old. • May continue into 3rd and 4th decade of life. • Pathogenesis: Obstruction of sebaceous follicles by sebum promotes proliferation of Propionibacterium acnes (anaerobe) • Distribution is on face, chest, and upper back.

Answer 155

Acne vulgaris

Question 156

2 types of acne

Answer 156

1. Obstructive • Closed comedones are “whiteheads.” Flesh- colored dome-shaped papules. • Open comedones are “blackheads.” Dilated pore filled with keratinous material (not dirt). 2. Inflammatory • Lesions progress from papules/pustules to nodules to cysts

Question 157

Acne vulgaris A. Risk factors B. 4 components C. Treatment

Answer 157

A. Risk factors: • Male sex • Puberty • Cushing’s syndrome • Oily complexion • Androgen excess B. Four components – Keratinization of lower portion of the follicular infundibulum with development of a keratin plug blocking outflow of sebum to skin surface – Hypertrophy of sebaceous glands with puberty (or increased hormonal stimulation) – Lipase-synthesizing bacteria (Propionibacterium acnes) colonizing the upper and midportion of the hair follicle, converting lipids within sebum to pro- inflammatory fatty acids – Inflammation of the follicle associated with release of cyotoxic and chemotactic factors C. Start with 1 drug and then add to regimen if no improvement within 6 weeks 1. Topical benzoyl peroxide-destroys bacteria and dries skin 2. Topical retinoids-causes peeling of skin which prevents pore clogging, good for comedonal acne (ex. tretinoin, adapalene, tazarotene) 3. Topical erythromycin or clindamycin-suppress P. acnes 4. Systemic antibiotics-tetracyclines, erythromycin, clindamycin, bactrim 5. Oral retinoids (isotretinoin) – for severe cystic acne unresponsive to the above treatments * Because this medication is a known teratogen, females must use two forms of birth control when on this medication, one of which must be a oral contraceptive. Two negative pregnancy tests prior to initiation of therapy and pregnancy counseling and testing repeated monthly. *Some oral contraceptives may improve patient’s acne

Question 158

• Chronic inflammatory disorder that affects blood vessels and pilosebaceous units • Occurs between 30-50 years of age and the etiology is unknown. • History – gradual onset of redness and progressing to telangiectasias, papules, and pustules • Triggers include sun exposure, alcohol, spicy foods, exercise, stress, and temperature extremes A. 4 stages B. Treatment C. Histology

Answer 158

Acne Rosacea A. 4 stages: 1. Flushing episodes (pre-rosacea) 2. Persistent erythema and telangiectasias 3. Pustules and papules 4. Rhinophyma – skin on nose becomes thick and greasy, hyperplasia of sebaceous glands, connective tissue and vasculature • Comedones are not found • Affects nose and cheeks including nasolabial folds B. • Diagnosis is most often made clinically. • Avoid alcoholic and hot beverages, extremes of temperature, and emotional stressors • Treat long-term with topical metronidazole gel and oral doxycycline C.Histology - Perifollicular infiltrate of lymphocytes surrounded by dermal edema and telangiectasia - In rhinophyma: hypertrophy of sebaceous glands And follicular plugging by keratotic debris

Question 159

Inflammation of fat lobules or the connective tissue septa separating fat lobules

Answer 159

PANNICULITIS

Question 160

Type of paniniculitis • Inflammatory reaction of the connective tissue septa separating fat lobules • Most common in females 20-30 • Not a disease but a reaction to various etiologies • Self-limited resolution in 6 weeks • Fever, malaise, and joint pain may precede the rash A. Presentation B. Causes C. Diagnosis and treatment D. Histology

Answer 160

Erythema Nodosum - reaction to some underlying condition A> Painful, red, subcutaneous, elevated nodules • Nodules are indurated and poorly circumscribed • Usually located on the anterior aspect of the tibia. • Bilateral but not symmetric B. Causes; reactive to some underlying condition Idiopathic, Strep infection, Sarcoidosis, Inflammatory bowel disease, Fungal infection, Pregnancy, Meds – (OCPs, sulfa, amiodarone, antibiotics), Syphilis, TB C. - Workup: Do CXR to r/o TB and sarcoidosis VDRL test to r/o syphilis CBC, ESR, CRP and cultures as appropriate Treat underlying condition - Treatment: Bed rest, leg elevation, NSAIDS, and heat for symptoms. Steroids only when infection excluded. D. Histology • Septal panniculitis (little to no necrosis of lobule) • Early: Widening of septa from fibrin, edema and neutrophilic infiltrate • Chronic: Mononuclear cells and granulomatous inflammation of septum with fibrosis

Question 161

Identify infection • Benign growths caused by infection of epidermal cells with human papilloma virus. • Generally occur in children and young adults. • Transmitted by skin to skin contact. • Lesions disrupt skin lines • Intralesional brown-black dots represent thrombosed vessels **types

Answer 161

WARTS A. Types 1. • The common wart (Verruca vulgaris) • Flesh-colored papule with a hyperkeratotic surface • Most common on elbows, knees, fingers, palms 2. • Flat wart (Verruca plana) • Flesh colored, slightly raised papules and flat surface. • Usually on chin, dorsum of hands, and legs. 3. • Plantar wart (Verruca plantaris) • HPV 1 • Flesh colored papule with hyperkeratotic surface • Warts found on underside of foot. May cause pain if on pressure areas. 4. • Anogenital wart (Condyloma acuminatum) • Most common STD, Types HPV 6 and 11 • HPV 16 and 18 can lead to cervical and genital cancer; head and neck cancer but do not cause condyloma • Appearance: Soft, fleshy pink papillomas on the genitalia, perineum, and anus.

Question 162

Histology of ? Exophytic • “Church spire” of “Verrucous” acanthosis • Koilocytes (cells with vacuolated cytoplasm – clearing around the nucleus) • Infected cells may show prominent keratohyline granules

Answer 162

Verruca vulgaris

Question 163

Warts A. Transmission B. Treatment

Answer 163

A. Transmission  Most warts are asymptomatic.  May bleed.  Most disappear in 1-2 years but may multiply or recur despite treatment. B. Treatment • Cryotherapy – may need >1 treatment, 60-75% • Duct tape – more effective than cryo in some studies • Salicylic acid (Compound W) – 60-80% effective • 5-Fluorouracil • Imiquimod – expensive, for recalcitrant lesions • Podophyllin for genital warts • Pare lesion down or soak to allow better penetration of topical medication.

Question 164

• Common, self-limited viral infection in kids and sexually active adults • Caused by poxvirus • Transmitted via skin-to-skin contact and is highly contagious. A. transmission and presentation B. Treatment C. Histology

Answer 164

Molluscum contagiosum A. • Asymptomatic smooth, dome-shaped papules with central umbilication. • Lesions are flesh-colored and translucent. • Papules have a cheesy core that can be expressed. • May occur singly or in groups. • Occur anywhere on kids and genitals of sexually active adults. B. • Spontaneously remit in a few months. • In HIV patients, lesions can be extensive, grow very large and be refractory to treatment. • Treatment – cryotherapy, curettage, salicylic acid C. • Cup-shaped lesion with scalloped border • Verrucous acanthosis (epidermal hyperplasia) • Molluscum bodies in cells of stratum corneum and stratum granulosum (ovoid, homogeneous, cytoplasmic inclusion bodies)

Question 165

• Common, highly contagious, superficial bacterial infection of the skin • Children, occ. adults • Two forms – Nonbullous and bullous • Nonbullous – Most common – Face and extremities – Papules progress to vesicles on erythematous base – When vesicles rupture causes typical “honey-colored crust” A. Bullous where? Organism? B. Histology and treatment

Answer 165

IMPETIGO A. • Bullous – Young children – Vesicles enlarge to form flaccid bullae with – Clear, yellow fluid contents, later becomes darker and more turbid; ruptured bullae leave a thin brown crust – Trunk is more frequently affected. • Staphylococcus aureus is most common cause of either kind B. • Histology: Accumulation of neutrophils beneath stratum corneum • Treatment: – Topical – mupirocin (Bactroban) or hydrogen peroxide cream for limited number of lesions – Oral antibiotics for bullous type

Question 166

• Common in school age children, nursing home patients, and less developed countries. • Patients present with the worst itch they’ve ever had. • Incubation time is about 1 month so contacts may not be symptomatic A. Presentation B. Transmission C. Diagnosis D. Treatment

Answer 166

SCABIES ; Infection with Sarcoptes scabiei A. Presentation • Predilection for finger webs, wrists, and penis. • Spares head, neck, palms, and soles. • Linear burrows with a dark dot at one end representing path of female mite in skin. • Small inflammatory papules and excoriations predominate. B. • Highly contagious – skin contact, towels, linens • Mites tunnel in epidermis, lay eggs, and deposit feces. Very few mites present. • Eggs and feces causes delayed type IV hypersensitivity reaction causing intense itching usually at night. C. Diagnosis • Look for burrows on hands, wrists, etc. • Suspect in anyone with persistent, generalized, severe pruritis. • Confirm diagnosis by scraping burrow with a scalpel. Look under microscope to detect mites, ova, or feces. D. Treatment • Topical: 5% permethrin cream • Oral: ivermectin, two doses as effective as permethrin • Treat all close contacts and wash all linens and underwear.

Question 167

6 functions of the skin

Answer 167

• Protection • Thermoregulation • Immune responsiveness • Biochemical synthesis • Sensory detection • Social/Sexual communication

Question 168

Methods of dermatologic drug administration **exclusively a diffusion process **what is the rate limiting step?

Answer 168

Percutaneous absorption; EXCLUSIVELY DIFFUSION - A concentration gradient is maintained with the highest concentration of a drug in the stratum corneum and the lowest in the subcutaneous side of the dermis - Substances must pass through the stratum corneum and subsequent epidermal layers to the dermal- epidermal junction in order to become biologicallu active. **Permeation through the stratum corneum is the RATE- LIMITING STEP.

Question 169

Other factors affecting percutaneous absorption **the first factor and most important is fick’s law of diffusion

Answer 169

Others 2. INTACT SKIN; Diseased or non-intact skin results in increased percutaneous absorption and increased transepidermal water loss. 3. AGE • Infants= Increased skin surface/body mass ratio 3 times that of adults, permitting EASIER SYSTEMIC TOXICITY. • Increased permeability-preterm infants • Full-term = Adults • AGED SKIN MORE PERMEABLE 4. ANATOMICAL SITE - HIGHEST rate of drug penetration in; Scrotum, post-auricular, eyelid> scalp>soles, palms - Increased absorption in body fold areas - Hair follicles and sebaceous glands –diffusion shunts 5. TEMPERATURE; increased temperature = increased diffusion = increased percutaneous absorption 6. FREQUENCY AND DURATION OF APPLICATION - Successive days of treatment increases % of absorption - Tachyphylaxis can occur after repeated steroid application (diminished biological effect after repeated usage) 7. PROPERTIES OF PENETRANT - pH and solubility – relative solubility in vehicle and in S. corneum (partition coefficient) is DIRECTLY proportional to amount of drug penetration. 8. VEHICLES 9. OTHER

Question 170

Topical dermatologic therapy - GLUCOCORTICOSTEROIDS 1. Actions (7) 2. Side effects (8)

Answer 170

1. Actions • Induce protein synthesis • Vasoconstriction • Decreased permeability • Decreased inflammation • Lysosome stabilization • Decreases arachidonic acid –decreases prostaglandins/cytokines • Decreased mitosis 2. Side effects • Skin Atrophy • Rosacea; acne type (when you use topical steroid for long time) • Infection • Striae • Decreased plasma cortisol levels • Cushings • Cataracts • Tachyphylaxis **Granuloma gluteala infantum; reddish-purple nodules in inguinal folds, scrotum, buttocks, medial thighs. 2-9 months of age. Associated with use of steroid creams and chronic candida infections - start with small dose in infants

Question 171

Identify principles of topical therapy

Answer 171

• Diagnose and assess the type of cutaneous eruption • Understand the principles of topical therapy • Understand dermatological vehicles and differences between them • Know pharmacologic MOA of drugs used**** (before you prescribe any medication)

Question 172

Topical therapy 1. Type of vehicles 2. Criteria of effective vehicle

Answer 172

1. Types of vehicles A. Liquids; lotions, shake lotions, solutions, aerosols/sprays B. Solids; ointment, creams, gels, pastes, powders 2. Criteria • Cosmetic elegance • Odor • Easy incorporation • Inert • Non-toxic • Non-allergenic - cost

Question 173

Identify topical drug method • Used in acute dermatoses (exudation, crusting, erosions, infection, ulcers) • Actions: drying, cooling, evaporation, cleansing, debridement, vasoconstriction (decreased heat and itching)

Answer 173

Soaks/baths/compress/astringents • Baths/soaks-widespread dermatoses • Wet dressings (compresses)- gauze or cloths soaked in water or solutions for localized areas (open-wet, closed-wet, wet to dry) • Agents- water, astringents (saline, acetic acid)

Question 174

• An acute, delayed, or transient inflammatory skin response to sunlight or artificial sources. • Redness, pain, blisters, swelling, itching • Can have fever, headache, chills, weakness- in severe sunburn, pulse rate is rapid • Medications: Acne meds- tetracycline, doxycycline, minocycline, bactrim (sulfa), ibuprofen, naproxen **Identify treatment

Answer 174

SUNBURN TREATMENT: Cool wet dressings(pillowcases),topical cortisone creams, pain relief-tylenol, aspirin, ibuprofen

Question 175

Fight against skin cancer 1. What is number 1 modifiable risk factor for skin cancer 2. UVR associated with what cancer? 3. Important risk factors? 4. What prevention programs needed? **incidence and mortality rate of skin cancer

Answer 175

1. Ultraviolet radiation (UVR) is the number 1 modifiable risk factor for skin cancer. 2. Epidemiologic evidence supports association of UVR with development of non-melanoma and melanoma skin cancer. 3. Sun exposure and sunburns in early life especially are important risk factors. 4. Effective skin cancer prevention programs needed . **1 in 5 Americans will get skin cancer **1 person dies every hour of a melanoma

Question 176

Identify cases of dermatologic conditions (10) 1. Use Hawaiian extract shampoo to wash her face. Yellow crusting on face, painful, miserable 2. Type of dermatitis - from betadine application in surgery or poison ivy 3. Dew drops on a rose petal 4. Around the eye 5. Yeast infection (moist area) 6. Fungi 7. Fungi on 1 hand and both feet 8. Affect body, scalp everywhere 9. Severe drug eruption - can result in death 10. Ulcer with pigmentation (never healed)

Answer 176

1. CHEMICAL BURN SECONDARY TO PRESERVATIVE IN SHAMPOO 2. ALLERGIC CONTACT DERMATITIS “RHUS DERMATITIS”; delayed type hypersensitivity reaction 3. VARICELLA “CHICKEN POX” 4. HERPES ZOSTER “SHINGLES” 5. INTERTRIGO SECONDARY TO CANDIDA ALBICANS INFECTION 6. BULLOUS TINEA PEDIS 7. TINEA MANUM DERMATOPHYTE INFECTION 8. PSORIASIS 9. BULLOUS DRUG REACTION TOXIC EPIDERMOLYSIS NECROSIS (PHENOBARBITOL) 10. Malignant Melanoma

Question 177

Identify - fungi that keratinized outer layers of skin, hair and nails - infections caused by these organisms elicit little or no host immune response and are non destructive and thus asymptomatic - only of cosmetic concern and are easy to diagnose and treat **which affect skin **which affect hair

Answer 177

Superficial mycoses 4 types 1. Pityriasis versicolor 2. Tinea nigra 3. Black Piedra 4. White piedra **1 and 2 affect skin. 3 and 4 affect hair

Question 178

Identify type of superficial mycoses A. Occurs worldwide - topical and subtropical - human host - young adults - asymptomatic B. Identify. 1. causative agent 2. unique risk factor 3. general xters 4. affected tissue 5. clinical features

Answer 178

Pityriasis versicolor (superficial fungus) **Causative agent - malassezia furfur 1. Etiological agent - Malassezia Furfur (pityrosporum orbiculare) 2. Unique Risk factor: Condition that reduces the rate of desquamation, that is shedding of epidermal cells, predisposing factors; poor nutrition, excessive sweating and pregnancy 3. General Characteristics - A lipophilic, yeast like organisms. It is a part of normal flora, found in areas of body rich in sebaceous glands. 4. Tissue Affected - Skin 5. Clinical features -Hyper pigmented or hypopigmented macular lesions that scale readily, giving it chalkybranny appearance, that occurs most frequently on the upper torso, arms and abdomen

Question 179

All factors affecting percutaneous absorption VARY INDIVIDUALLY. **identify factors affecting percutaneous absorption ******DIRECT VS INVERSE RELATIONSHIP

Answer 179

1. Flicks law of diffusion** A. INCREASING: - D (DIFFUSION COEFFICIENT) - C (CONCENTRATION OF DONOR DRUG) RESULT = M (amount of drug in receptor phase) is INCREASED THIS IS A DIRECT RELATIONSHIP**** B. INCREASING: h – thickness of the skin RESULT: M (drug amount in receptor phase) is DECREASED. THIS IS AN INVERSE RELATIONSHIP**** J = (Km Dm) / Th X C INCREASING: Km (solubility), Dm (diffusion), C (conc.) results in an INCREASE in J (amount of drug penetrating) INCREASING: Th (thickness of skin) results in a DECREASE in J (amount of drug penetrating)

Question 180

1. The following is characteristics of what? - dimorphic - lipophilic - opportunistic - interfere with melanin production - transient, superficial and scaly - also associated with seborrheic dermatitis and dandruff 2. Lesions of pityriasis versicolor - locations? - light skin vs dark skin - rare complication?

Answer 180

1. Mallasezia Furfur 2. Small hypopigmented or hyperpigmented macules - The upper trunk, arms, chest, shoulders, face, and neck are most often involved, but any part of the body may be affected. - The lesions are irregular, well-demarcated patches of discoloration that may be raised and covered by a fine scale. - Because M. furfur tends to interfere with melanin production, lesions are hypopigmented in DARK-SKINNED individuals. - In LIGHT-SKINNED individuals, the lesions are pink to pale brown and become more obvious when they fail to tan after exposure to sunlight. - Little or no host reaction occurs, and the lesions are asymptomatic, with the exception of mild pruritus in severe cases. - Infection of the hair follicles, resulting in folliculitis, perifolliculitis, and dermal abscesses, is a rare complication of this disease.

Question 181

Diagnosis and treatment of pityriasis versicolor

Answer 181

1. Diagnosis A. CULTURE not routinely done for diagnosis purpose - culture may be performed using synthetic mycologic media supplemented with olive oil as a source of lipid. - Growth of yeast like colonies appear after incubation at 30° C for 5 to 7 days. - Microscopically, the colonies are comprised of budding yeast like cells with occasional hyphae. B. yellow to yellow green fluorescence - WOODS LAMP I) Direct microscopic examination of KOH treated skin scrapings reveals fungal elements demonstrating the presence of yeast cells in clusters and short hyphal elements classical “spaghetti and meat balls” appearance. ii) Wood’s lamp - lesions appear pale yellowiii) culture - not routinely done.
2. Treatment - Preparation containing selenium disulfide, hyposulfite, thiosulfate or salicylic acid, ketoconazole (1% in cream)

Question 182

Identify superficial mycoses - superficial fungal infection of the stratum corneum. Hortaea (Exophilia) werneckii - children and adults most affected - NOT CONTAGIOUS **rule out diagnosis of malignant melanoma and Nevi (via 10-20% KOH - treated scraping - yeast like cells with hyphal fragments) - treat with azole cream **Common in; Africa Asia, central and South America - traumatic inoculation - asymptomatic well demarcated slowly expanding - **Gray to black dermarcated macular lesions - nonscaly macules with well defined borders on palms and soles

Answer 182

TINEA NIGRA; - Children and young adults are most often affected, with a higher incidence in females. - Tinea nigra appears as a solitary, irregular, pigmented (brown to black) macule, usually on the palms or soles (Figure 70-5). - There is no scaling or invasion of hair follicles, and the infection is not contagious. - Because of its superficial location, there is little or no discomfort or host reaction. - Because the lesion grossly may resemble a malignant melanoma, biopsy or local excision may be considered. - Such invasive procedures may be avoided by a simple microscopic examination of skin scrapings of the affected area

Question 183

Identify type of mycoses - delayed type hypersensitivity - infections extend deeper into the epidermis as well as invasive hair and nail disease - no immunity develops with tinea or ringworm - have a common host ; get it from kissing new puppy or kittens **presentation

Answer 183

Cutaneous mycoses

The cutaneous mycosis involves disease of the skin, hair and nails.

Generally affects keratinized layers of the integument and its appendages. They can use keratin as nitrogen source. The organisms which participate in these infections are known as DERMATOPHYTE.

The clinical manifestation of these disease are also referred as RINGWORM or tinea

Different species of dermatophyte varies markedly from one ecological niche to another. i) Geophilic - soil ii) Zoophilic - lower animals and birds. iii) Anthropophilic - humans only

Question 184

Cutaneous mycoses

Dermatophytes infecting humans **classified in what 2 categories

**How are dermatophytosis spread?

Answer 184

1. Morphological; depending on the sporulation patterns (microporum, trichophyton, spidermophyton) 2. Clinical; depending on location of the lesion* aka ringworm or tinea

***The term DERMATOPHYTOSIS refers to a complex of diseases caused by any of several species of taxonomically related filamentous fungi in the genera Trichophyton, Epidermophyton, and Microsporum.

These fungi are known collectively asthe dermatophytes, and all possess the ability to cause disease in humans and/or animals.

*** All have in common the ability to invade the skin, hair, or nails. In each case, these fungi are keratinophilic and keratinolytic and so are able to break down the keratin surfaces of these structures. In the case of skin infections, the dermatophytes invade only the upper, outermost layer of the epidermis, the stratum corneum. Penetration below the granular layer of the epidermis is rare. Likewise with hair and nails, being part of the skin, only the keratinized layers are invaded.

The clinical signs and symptoms of dermatophytosis vary according to the etiologic agents, the host reaction, and the site of infection. keratin they prefer.
I) Microsporum - Keratin of skin and hair. (fusiform or spindle shape conidia)
ii) Epidermophyton - Keratin of skin and nails (Snow shoe or beaver’s tail
macroconidia with thin smooth walls)
iii) Trichophyton - Keratin of hair, skin and nail. (Pencil or cigar shaped
microconidia more in number than macroconidia)

Question 185

Cutaneous mycoses

Tinea (6 major types)?

**which type of tinea is related to another fungi infection?

*type of sensitivity

**How do you diagnose

Answer 185

** The various forms of dermatophytosis are referred to as “tineas” or ringworm. Delayed type sensitivity. No classical humoral or cell mediaed protective immunity.

1. Tinea capitis (scalp hair); annular ring structure. Hair becomes gray, dull and brittle due to ectothrix invasion of hair, hair breaks off near base of shafts. more common in prepubescent children
2. Tinea Barbae (beard)
3. Tinea Pedis (feet)
4. Tinea cruis (groin) “Jock itch”
5. Tinea magnum (hands); contact with another site of infetion esp feet or groin. Direct contact with an infected animal or soil
6. Tinea unguium (nail) **compared with candida infections ONYCHOMYCOSIS (feet). Trichophyton rubru is most common causative agent of T.unguium (nail). diagnose with wood’s lamp - flourescent yellow to green. fingernail fungal infections cure more quickly

*Diagnosis

• KOH prep (of hair or scalp scrapings)
• Wood’s lamp test (light that use long wave UV light - fungus will glow). detect fungal scalp or skin infection
• Growth on specialized media (special pattern of growth in culture and prodcution of macro conidia and micro conidia)

**Treatment

Local - (topical), miconazole, clotrimazole and econazole.
Oral antifungal agents with systemic activity against dermatophytes include; griseofulvin, itraconazole, fluconazole, and terbinafine

Question 186

Identify type of mycoses

• infection involves deeper layers of the dermis, subcutaneous tissue or bone
• associated with some form of trauma (splinter, rose bush throne or insect bite)
• affect feet, hands, arms and buttocks more often (most prone to trauma)
• ALL PRODUCE GRANULOMA

**Identify 4 major kinds of infection

Answer 186

Subcutaneous fungal infection

Subcutaneous mycoses include a wide spectrum of fungal infections, which are implanted at the site of trauma. The infections initially involve the deeper layers of the dermis, subcutaneous tissue or bone. All the fungi that cause subcutaneous infection in humans are found as saprobes throughout the world.

Four major kinds of infections:
Sprotrichosis
Chromoblastomycosis
Phaeohyphomycoisis
Mycetoma

Question 187

1. Examples of subcutaneous fungal infection
2. Differential Dx you should rule out?

Answer 187

1. SPOROTRICHOSIS; Lymphocutaneus sporotrichosis (common in US)
2. CHROMOBLASTOMYCOSIS
3. Subcutaneous phaeohypomycosis
4. Mycetoma

*Differential diagnosis to rule out

• atypical mycobacterial infection, especially M.marinum
• Nocardia infections, particularly N. brasiliensis
• Leishmania brasilensis infection
• Tularemia

Question 188

Identify type of subcutaneous mycoses - rose gardener’s disease (CIGAR SHAPE YEAST CELL in KOH). ASTEROID BODIES represent the host’s imune response

• A chronic infection that ordinarily begins as a subcutaneous nodules at the site of injury and progress to lymphatic channels

**5 types of infection

*What determine what type of infection develops

Answer 188

sporotrichosis

**Causative agent - Sporothrix schenckii. it is a dimorphic fungus - S. Schenckii and is common in the USA. it affects the skin and lymphatic system

It is a chronic infection characterized by nodular lesions of
the cutaneous or subcutaneous tissues and adjacent lymphatics that suppurate, ulcerate, and drain.

Sporotrichosis can be separated into five types of infection: Lymphocutaneous (involve lymph node), fixed cutaneous (dont involve lymph node), mucocutaneous,
disseminated, and pulmonary.

The portal of entry of the fungus, the dose, and the effectiveness of the host’s response determine which type of infection develops

Asteroid bodies represent the host’s immune response. The eosinophilic material is a complex of antigenic material from the fungus and the antibody protein from the host

Treatment:

Potassium iodide (oral in Milk) (cutaneous infection)
Amphotericin B (disseminated infection)

Question 189

Identify type of subcutaneous mycoses

• most common in tropical and subtropical areas
• infections are often seen in workers injured with woods
• colored lesions that start out scaly and become raised cauliflower-like lesion
• sclerotic bodies (medlar bodies); copper colored spherical yeast in tissue

**Identify; causative agent, clnical features

Answer 189

CHROMOBLASTOMYCOSIS; chronic infection of skin

Etiological agent - Is caused by dematiaceous (pigmented) fungi (phialophora and cladosporium). The most common agent is Fonsecaea pedrosi.

Clinical features - These infections are often seen in workers injured with woods. Characterized by the development of papules at the site of inoculation which over the years becomes verrucous (warty) crusted. At the progression of the
lesion: appears to vegetate, “Cauliflower like” appearance, It is characterized by the development of Verrucous (Warty) nodules at the site of inoculation.

Diagnostic features- Presence of pigmented fungi in tissue sections or pus. The thick-walled cells are called sclerotic bodies or medlar bodies.

Culture

Treatment
I) surgical excision in the early stages
ii) 5-flucytosine (oral)

Question 190

Identify type of subcutaneous mycoses

Causative agents:
The etiologic agents of phaeohyphomycosis are numerous and varied in their generic classification. Majority of them belongs to the dematiaceous hyphomycetes and they all produce melanin in the cell wall. (Subcutaneous infections with dark- walled hyphae)

Diagnosis:
Periodic acid-Schiff (PAS) or methenamine silver stain: Dark-walled hyphae

Treatment:
Surgical resection of well-localized lesions
Amphotericin B , Oral ketoconazole and itraconazole

Answer 190

Subcutaneous phaeohyphomycosis dermatiaceous molds

“Phaeo” is the Greek word denoting a “Dark” They are heterogeneous group of infections Characterized by presence of darkly -pigmented fungal elements.

These infections include cerebral or subcutaneous infections. These fungi can also cause chronic paranasal sinusitis, prosthetic valve endocarditis, keratomycosis and widely disseminated infections.

Question 191

Identify type of subcutaneous mycoses

Etiological agent: Petriellidium boydii is the most common eumycotic mycetoma in the United State and Europe.

Symptoms: Massive induration with draining sinuses

Diagnosis: Macroscopically examination of sclerotia. Sclerotia are mounted in sterile saline and then crushed. Microscopically fungal hyphae with many intercalary swollen cell can be seen.

Treatment: difficult to treat with antimycotic drugs. Amputation is usually the final
action.

Answer 191

Fungal mycetoma **Not dimorphic

Mycetoma is a clinical syndrome characterized by tumefaction, draining sinuses, and sclerotia (granules, grains). Maduromycosis, madura foot Deforming infection on the foot or the hand May take years to develop. The infections starts as a small indurated
subcutaneous papule. The tissue exudates white,yellow or black granules (sclerotia)

Question 192

**Presence of yeast cells that assume a cigar shape

Answer 192

SPOROTRICHOSIS

Question 193

Describe bone pathways

1. Rank pathway
2. M-CSF pathway
3. WNT/beta catenin pathway

**3 important bone cells

Answer 193

1. Rank pathway - RANK ligand (RANKL) on OB and marrow stroma cells RANK receptor on OC precursor - Allow OC generation and survival **OPG (osteoprotegrin) block the rank/rankL interaction
2. M-CSF pathway - M-CSF secreted by OB - M-CSF receptor allows OC generation and survival
3. WNT/beta catenin pathway •WNT from marrow stromal cells •LRP5 and LRP6 OB receptor bind WNT protein - Secrete OPG - Block RANK **osteocytes (has nuclei), osteoclasts, active osteoblasts (make bone)

Question 194

Basic multicellular unit

Answer 194

Balance in the 3 bone cells

• Local collection of OB, OC and Osteocytes
• Early bone formation dominates
• Adult undergo remodeling: 10% year turnover
• Peak bone mass: Early adulthood

Question 195

Bone composition **main one? ** 2 TYPES OF bones

Answer 195

• CALCIUM HYDROXYAPATITE
• Organic matrix mostly type 1 collagen
• Types of bone

A. Woven bone: Random collagen deposition

B. Lamellar bone: Ordered collagen deposition

• Compact bone
• Spongy bone (calcinous)

Question 196

Bone enzymes

Answer 196

1. Osteopontin (osteocalcin): Unique to bone*** • Levels parallel osteblast activity 2. Alkaline phosphatase: From osteoblasts • Also in LIVER and PLACENTA **elveated in growing child, liver disease, pregnant woman

Question 197

Identify bone type

1. **ALWAYS PATHOLOGICAL IN ADULT (not normal) - always look pink Random collagen deposition •Rapid bone growth eg healing fracture •Resists forces all directions •Always pathologic in adult
2. •Ordered collagen deposition •Replaces woven bone •Stronger than woven bone

Answer 197

1. Wooven bone
2. Lamellar bone

Question 198

1. Bone formation 2. Location***

Answer 198

BONE FORMATION: Intramembranous ossification

• Direct from mesenchyme
• Appositional growth

LOCATION LOCATION LOCATION

• Epiphysis: Distal to growth plate
• Metaphysis: Beneath growth plate
• Diaphysis: Center

Question 199

Identify bone abnormality

1. Local problems in migration of mesenchyme and their condensation
2. Global defect in regulation of skeletal organogenesis

Answer 199

1. Dysostosis
2. Dysplasia

**6 fingers or branchydactyly; HOXD13 defect

Question 200

Identify bone abnormality Autosomal dominant •RUNX2 (CBFA1) transcription factor defect - Short stature - Abnormal clavicles - Supernumery teeth - Wormian bone

Answer 200

CLEIDOCRANIAL DYSPLASIA **no collar bones

Question 201

Identify bone abnormality •Growth plate defect from paracrine cell defect •Reduced chondrocyte proliferation in growth plate •FGFR3 point mutation: Gain of function: Inhibits cartilage growth •90% are spontaneous mutation •Most common from paternal allele •Autosomal dominant • Growth plate zones are narrowed and disorganized; Premature bone deposition • Appositional and intramembranous bone formation continues; Create relatively thick cortical bone **presentation

Answer 201

ACHONDROPLASIA **FGFR3 point mutation **Paracrine cell defect Presentation •Short stature •Short proximal limbs •Normal trunk length •Enlarged head with bulging forehead •Depression root of nose •Normal longevity, intelligence and reproductive status

Question 202

Identify bone abnormality **Most common lethal dwarfism with 1/20,000 births •FGFR3 mutation gain of function •Micromelic short bowed limbs •Frontal bossing with macrocephaly •Small underdeveloped chest with bell-shaped abdomen; respiratory failure •Diminished chondrocyte proliferation

Answer 202

THANATOPHORIC DWARFISM

type 1 - bowed femur

type 2 - cloverleaf skull

Question 203

LRP5 and its effects on WNT/beta catenin pathway

Answer 203

1. LRP5 • Receptor activates WNT/β-catenin in OB - Production of OPG (blocks RANKL) - Increases bone mass • Gain of function; cannot up regulate OC - Autosomal Dominant Osteopetrosis type 1 • Diseases of inactive LRP5 - Osteoporosis pseudoglioma syndrome - Skeletal fragility - Loss of vision
2. WNT/beta catenin pathway •WNT proteins from marrow stromal cells •LRP5 and LRP6 receptors on OB - Activate β-catenin - Secrete OPG

Question 204

• “Marble bone disease” • Diffuse systemic bone sclerosis • Reduced osteoclast bone resorption: - Cannot acidify pit eg Carbonic anhydrase II (CA2) deficiency - Defect in RANKL: Not enough OC activity - LRP5 gain of function • Spectrum from autosomal dominant benign to autosomal recessive “malignant”

**what is the problem here

• presentation
• what form is most common?

Answer 204

OSTEOPETROSIS

1. Bone deposition replaces medullary cavity • No room for hematopoiesis; extramedullary hematopoises • Bulbous long bones; Erlenmeyer flask deformity • Narrow neural foramina • Brittle bones
2. Autosomal dominant benign osteopetrosis • Adolescent or adulthood • Multiple fractures • Mild anemia • Hepatosplenomegaly • Mild cranial nerve defects • Can be treated with bone marrow transplant

Question 205

Identify bone abnormality **CONFUSED WITH CHILD ABUSE (FRACTURES**) • Group of Type 1 Collagen Diseases • “Brittle bone disease” • Affects other areas rich in type 1 collagen • Mutation of α1 or α2 chains - Quantitative decrease - Qualitative defect • Most common type is autosomal dominant • Extreme skeletal fragility vs child abuse

**identify forms (type I, II-IV)

Answer 205

OSTEOGENESIS IMPERFECTA

A.Type I: Autosomal dominant**** • Normal stature with less fractures after puberty • BLUE SCLERAE from translucency of sclera • Dentinogenesis imperfecta from dentin defect • Hearing loss from abnormal ear bone and sensorineural deficit • Joint laxity • Compatible with normal lifespan

B.Types II-IV: Autosomal dominant to recessive with varying degrees of disease

Question 206

IDENTIFY bone abnormality • Increased bone porosity and decreased mass - Increased risk of fracture • Disuse osteoporosis; Local • Metabolic bone disease - Primary: Senile, postmenopausal, idiopathic - Secondary: Drugs, diabetes, endocrine disorders, malignancy liver or GI disease • X-ray can detect only after 30-40% of bone loss

**osteoporosis vs osteopenia

Answer 206

OSTEOPOROSIS **X-ray is a poor test to detect

• Osteopenia: Decrease bone mass
• Osteoporosis: Osteopenia to the point of risk of fracture

Question 207

Risks of osteoporosis (3)

Answer 207

1. Reduced physical activity • Disuse osteoporosis: Localized from loss of stimuli for bone remodeling • Problem with long term space flight
2. Genetic factors • eg Vit D receptor polymorphism
3. Nutrition • Calcium deficiency during growth stunts peak bone mass

Question 208

Identify bone abnormality • Skeletal mass peak: Young adult - Mostly hereditary determined by Vitamin D receptor, Collagen 1A1,Estrogen receptor, etc - Physical activity, strength, diet, hormone state • Slow decrease in bone mass over time: - Osteoblasts reduced metabolism • Cortex thinned on all surfaces - Cortex bone may look like cancellous bone

Answer 208

SENILE OSTEOPOROSIS “low turnover variant”

Question 209

Identify bone abnormality • 30 yrs post-menopause - 35% cortical and 50% trabecular bone loss - 1 in 2 women will have an osteoporotic fracture • High-turnover form of osteoporosis • ↓ Estrogen leads to ↑ inflammatory cytokines - ↑ RANKL and ↓ OPG; ↑ OC>OB activitiy - Estrogen replacement is protective - Vertebral body collapse

Answer 209

POSTMENOPAUSAL OSTEOPOROSIS **careful with estrogen cause it predispose you to breast and endometrial cancer

Question 210

Types of secondary osteoporosis

Answer 210

1. Hyperparathyroidism 2. Neoplasia 3. Multiple myeloma 4. Vitamin D deficiency 5. Anticoagulants 6. Corticosteroids (long term) 7. Immobilization

Question 211

Diagnosis and treatment of osteoporosis

**which is not a sensitive test

Answer 211

• X-ray: Not sensitive test • Serum levels of Calcium, Phosphorous, Alkaline phosphatase do not detect • Dual-energy absorptiometry (DEXA scan)
• Prevention - Exercise - Nutrition: Vitamin D, Calcium, - Drugs: Estrogen, bisphosphonates,

Question 212

Abnormal mineral homeostasis (4)

Answer 212

• RICKETS: Child vitamin D deficiency (chapter 9)
• OSTEOMALACIA: Adult vitamin D deficiency (chapter 9)
• HYPERPARATHYROIDISM: - PTH excess
• RENAL OSTEODYSTROPHY: - Chronic renal disease

Question 213

Abnormal mineral homeostasis

• Increased activity OC>OB
• Osteitis fibrosa cystica: Severe disease

**2 types

Answer 213

Hyperparathyroidism

1. Primary hyperparathyroidism • Most commonly from an adenoma
2. Secondary hyperparathyroidism (often from hypocalcemia) tends to be less severe

Question 214

Presentation of hyperparathyroidism

Answer 214

Entire skeleton affected • Subperiosteal resorption thins cortices • Loss of lamina dura around teeth • X-ray: Bone loss radial aspect of middle phalanges of index and middle finger • X-ray: Osteopenia • BROWN TUMOR • Bone replaced by fibrovascular tissue • Microfractures result in hemorrhage and healing • Granulation tissue, and hemosiderin

Question 215

Identify Abnormal mineral homeostasis

• Increased or decreased OC/OB activity - Delayed mineralization (osteomalacia) - Osteosclerosis - Osteoporosis • Hyperparathyroidism • Decreased Vitamin D conversion to 1,25-OH • Metabolic acidosis: ↑release of Ca++

Answer 215

RENAL OSTEODYSTROPHY

Question 216

Identify Abnormal mineral homeostasis • Mid adulthood Caucasians from US, Europe; 1% of US; 2.5% males in England • Most asymptomatic but may have pain • Easily fractured • 85% Polyostotic • 80% involve axial skeleton and proximal femur **describe different stages (3)

Answer 216

PAGET DISEASE

1. Osteolytic stage : Loss of bone mass • Osteclasts in haphazardly resorption pits
2. Mixed stage: Osteolytic and osteoblastic • Prominant osteoblasts and osteoclasts
3. Osteosclerotic stage: • Coarse thick irregular trabeculae • Hallmark: Mosaic pattern of lamellar bone: Jigsaw puzzle-like cement lines

Question 217

Identify Presentation of this disease • Warm skin over affected bone with hypervascularity; polyostotic can create AV shunting - High-output cardiac failure • Tumors - Benign: Giant cell tumor, giant cell reparative granuloma, extraosseous hematopoiesis - Malignant: Osteosarcoma and fibrosarcoma; 5-10% of patients with severe polyostotic disease • Treat: Calcitonin and biphosphonates

Answer 217

PAGET DISEASE • May present with pain from microfractures • Often incidental finding on x-ray • Increased Alkaline Phosphatase • Normal Ca and PO4 • Bone overgrowth can lead to - Cranial nerve palsy - Heavy skull to heavy to hold up - Severe secondary osteoarthritis - Chalk stick-type fracture (WHITE BRAIN IN X-RAY)

Question 218

Identify types of fracture

Answer 218

• Closed (simple)/Open (compound)
• Comminuted (fragmented)
• Displaced • Greenstick
• Pathologic: Secondary to disease
• Stress: Slowly developing from repeated loads, eg marching

Question 219

2 stages of healing for fractures 1. • Hematoma fibrin creates framework • Influx inflammation, fibroblasts, and capillaries • Osteoprogenitor cells activated • No rigidity; easily disrupted 2. • Woven bone is made • +/- cartilage for enchondral ossification • Maximum girth of callus 3 wks • Over time remodels to bear full weight

Answer 219

1. Soft tissue callus (procallus) 2. Boney callus

Question 220

Complications of fracture (3)

Answer 220

• Misaligned bone • Infected, displaced or devitalized bone leads to deformity • Pseudoarthrosis: Nonunion

Question 221

Identfiy bone abnormality • Infarction of bone and marrow • Mechanisms all create ischemia: - Vessel injury, eg mechanical, arteritis, emboli - Corticosteroids most common cause - Increased intraosseous pressure • Dead bone/fat is replaced by Ca++ soaps • Creeping substitution: Slow bone growth - Continued fractures and collapse of bone - Slough articular cartilage

Answer 221

OSTEONECROSIS (AVASCULAR NECROSIS)

Question 222

Below are causes of what bone abnormality • Idiopathic* • Corticosteroids* • Trauma • Infection* • Dysbarsim* (emboli in bone from diving) • Radiation • Connective tissue disorders • Pregnancy* • Gaucher Disease • Alcohol abuse • Chronic pancreatitis • Tumors • Epiphyseal disease • Sickle cell disease* and otheranemias

Answer 222

AVASCULAR NECROSIS

Question 223

Identify 2 types of Avascular necrosis

Answer 223

1. MEDULLARY INFARCT: • Geographic necrosis • Small silent and stable • Large painful eg dysbarism, sickle cell
2. SUBCHONDRAL INFARCT • Chronic pain • Wedge-shaped subchondral bone - Often CRACK beneath preserved cartilage - Overlying cartilage nurtured by synovial fluid • Secondary collapse lead to osteoarthritis

Question 224

Identify bone abnormality

• Inflammation almost always from infection - Bacteria, virus, fungi, parasite - Pyogenic; almost always bacteria • Bacteria reach bone by - Hematogenous (most common in children) - Direct extension - Implantation • Classic x-ray: - Lytic bone lesion with surrounding sclerosis

Answer 224

OSTEOMYELITIS

**Common with diabetes (in feet) - lead to amputated toe/feet

Question 225

Identify bone abnormality

• 50% culture negative • S aureus: 80-90% of culture positive • E coli, Pseudomonas, Klebsiella; GU infections and iv drug abusers • Mixed infections; Surgery or compound fractures • H influenzae and Group B strep in infant • Salmonella in sickle cell disease

Answer 225

PYOGENIC OSTEOMYELITIS

• Initial acute inflammation and necrosis
• Location influenced by blood supply:
• NEONATE: Metaphysis and/or epiphysis. Can spread into joint through articular surface or adjacent structures
• CHILDREN: Metaphysis; Subperiosteal abscess
• ADULT: Epiphyses and subchondral bone

Question 226

Types of conditions from pyogenic osteomyelitis

Answer 226

1. Sequestrum: Dead piece of bone
2. Later chronic inflammation and fibrosis • Develop rimed by reactive bone • Brodie Abscess: Small intraosseous abscess often in the cortex
3. Involucrum: Reactive surrounding bone
4. Sclerosing osteomyelitis of Garré: • In jaw with extensive new bone formation

Question 227

Presentation of pyogenic osteomyelitis

Answer 227

• Presentation varies - Acutely sick to unexplained fever - Local pain - Draining sinus; Can develop squamous cell carcinoma
• 5-25% become chronic osteomyelitis - Complications include; Pathologic fracture, Sarcoma

**ACUTE OSTEOMYELITIS CAUSED BY STREP

Question 228

Type of osteomyelitis

Third world, immunocompromised • Third world: Adolescents and young adults • US: Older or immunocompromised • 2% with TB have osteomyelitis • Most common Potts Disease: L/Tspine • Break through discs to other vertebrae; scoliosis ad hypnosis • Knees and hips second most common

Answer 228

TB OSTEOMYELITIS

Question 229

Identify bone abnormality

• T pallidum and T pertenue (yaws) • CONGENITAL: • Affected at 5 mo; fully developed at birth • Localize at enchondral ossification centers (osteochondritis) and • ACQUIRED of the bone • Involves bone in tertiary phase, • Nose (saddle nose), palate, skull, tibia (saber shin), vertebrae, periosteum (periostitis) hands/feet

Answer 229

SYPHILIS OF THE BONE Others **Saddle nose (go in); caused by trauma and cocaine **Saber shine; extremity go in

Question 230

Types of bone tumors excluding metastatic tumors (5)

Answer 230

• Hematopoietic
• Matrix producing - Chondrogenic - Osteogenic
• Unknown histologic type (10%)
• Fibrogenic
• Misc: Vascular, lipogenic, neurogenic,

Question 231

BONE TUMORS excluding hematopoietic

**Which is more common (benign or malignant)

1. Most common (2)
2. Most common benign tumors (2)
3. Most common malignant

Answer 231

• Benign more common than malignant

1. Most common are
   - Matrix producing (bone and cartilage)
   - Fibrous tumors
2. Most common BENIGN TUMORS
   - Osteochondroma
   - Fibrous cortical defect
3. Most common MALIGNANT TUMOR
   - Osteosarcoma > chondrosarcoma and Ewings

Question 232

Bone tumors

**hereditary vs other associations

Answer 232

Benign tumors mostly in children/young adults; elderly is likely to be malignant

HEREDITARY associations: • Li Fraumeni syndrome (p53 mutation) • Hereditary retinoblastoma (Rb mutation)

OTHER associations: • Paget Disease • Metal prosthesis • Chronic osteomyelitis • Infarcts

Question 233

Presentation of benign tumors

Answer 233

• Benign tumors commonly present as incidental finding on x-ray • May present as pain as slow growing mass • May present as pathologic fracture

Question 234

Bone tumor location 1. Metaphysis 2. Epiphysis 3. Diaphysis 4. Epiphysis/Metaphysis

Answer 234

1. Metaphysis • Osteoid osteoma (pain at night) • Osteochondroma • Osteosarcoma • Chondroma • Fibrous dysplasia • Fibrous cortical defect • ABC
2. Epiphysis • Clear cell chondrosarcoma • Chondroblastoma
3. Diaphysis • Ewing Sarcoma • Fibrous dysplasia
4. Epiphysis/Metaphysis • Giant cell tumor • Aneurysmal bone cyst

Question 235

Identify bone tumor

• Subperiosteal or endosteal cortex surface • Common in sinuses, skull and face • Bosselated, round, oval or sessile • Woven and lamellar bone +/- marrow • Incidental unless obstructing or impinging • eg impinge on brain or obstruct sinus • Gardner Syndrome – multiple osteomas • Intestinal polyps, epidermal cysts, and fibromatosis • *** See GI chapter

Answer 235

OSTEOMA

Question 236

Osteiod osteoma vs osteoblastoma

Location? Bones? size? Pain? ASA/NSAID relief? Age? X-ray? Histology? Treat?

Answer 236

1. Osteoid Osteoma; located in metaphysis cortex. bones are femur/tibia 50% and humerus/hands/feet. size is <2cm. Pain is intense at night. use ASA/NSAID for pain relief. occur in age 20s. X-ray show central nidus (lucenc); +/- adjacent bone scleross and +/- central density. histology show osteoblasts on woven bone + loose vascular CT. Treat with radioablation
2. Osteoblastoma; bones are vertebrae posterior. size is >2cm. Dull ache. no pain relief. also in age 20s. x-ray show radiolucent. histology show osteoblasts on woven bone + loose vascular CT. treat with excision/curretage

Question 237

Identify bone tumor

**MAKING MALIGNANT BONE - most occur in puberty and young adult ; distal femur - seen with paget’s disease in elderly

Answer 237

OSTEOSARCOMA

• Most common nonhematopoetic malignant primary bone tumor • By definition makes osteoid • Bimodal age - 75% in < 20 years (50% knee) - Elderly; • Associated with Paget’s Disease • Flat and long bones • Bone infarction, prior irradiation, metal prosthesis • Painful enlarging mass

Question 238

Osteosarcoma

1. Grouped by>
2. Most common
3. Presentation

Answer 238

1. • Grouped by • Location: Medulla, cortex, periosteium • Degree of differentiation • Primary vs secondary • Histology – amount and types of matrix
2. Most common: • Primary, solitary, long bone (knee) • Metaphysis medulla • Poorly differentiated with boney matrix
3. • Grey-white with hemorrhage, necrosis • Destroy adjacent bone and soft tissue • Rare to breach epiphyseal plate or joint • X-ray: - Destructive with mixed lytic and blastic - Breaks through cortex; Codman triangle: Tumor lifts periosteum • May have chondroid element

Question 239

Complication of osteosarcoma **genetics - survival rate

Answer 239

• Blood borne metastasis - 10-20% have lung metastasis at presentation - Lungs, bones, brain • Long term survival 60-70% • Genetics - Hereditary retinoblastoma: RB gene defect - Li-Fraumeni Syndrome: p53 gene defect

Question 240

Identify bone tumor

• Mushroom-shaped cartilage-capped - Enchondral ossification - Adolescence early adult • Metaphysis: near growth plate of long tubular bones; especially the knee • Marrow and cortex continuity • Multiple Hereditary Exostosis - Autosomal dominant (“double hit”) - EXT1 or EXT2 gene

Answer 240

OSTEOCHONDROMA “EXOSTOSIS”

Question 241

Identify bone tumor

• Slow growing mass (grow in soft tissue and start causing problems) • Pain if impinges on nerve or fracture • Stop growing with closure of growth plate • Rare risk of chondrosarcoma; Increased risk if Multiple Hereditary Exostosis

Answer 241

OSTEOCHONDROMA

Question 242

Identify bone tumor

Benign hyaline cartilage tumors - Enchondroma: Medullary cavity • Solitary in metaphysis of tubular bones • Most common in hands and feet • Most common intraosseous cartilage tumor • Subperiosteal chondroma (Juxtacortical chondroma): Surface of bone Age 20-50

Answer 242

CHONRDROMA

Question 243

Bone tumors • Less than 3 cm grey-blue • Nodules of hyaline cartilage with peripheral enchondral ossification • Most often incidental finding • Rarely transform to sarcoma • Increased for sarcoma transformation • Enchondromatosis (Ollier Disease): • Maffucci Syndrome: Enchondromas with hemangiomas **what do you see in X-ray - most common tubor of what?

Answer 243

ENCHONDROMA **Most common bone tumor of PHARYNX • X-ray well-circumscribed lucency with a thin rim of dense bone • If calcified matrix: Irregular opacities • Most common bone tumor of phalynx

Question 244

Identify bone tumor • Rare, seen in teenagers • Most common in knee epiphyses • Painful • X-ray: Well-demarcated lucency • Chondroblasts • Rare lung metastasis after curettage or fracture

Answer 244

CHONDROBLASTOMA

Question 245

Chondrosarcoma

• classification
• presentation

Answer 245

• By definition, no malignant bone formation

Classification by LOCATION • Intramedullary • Juxtacortical and surface

Classification by HISTOLOGY • Conventional (hyaline and/or myxoid) • Clear cell • Dedifferentiated • Mesenchymal • Half as common as osteosarcoma • >40 years • Clear cell and mesenchymal occur teens/20s • Central skeleton: pelvis, shoulder, ribs • Rare to arise in distal extremities • Clear cell: Long tubular bone Epiphyses • 15% arise in enchondroma • Higher risk with multiple enchondromas, and osteochondroma

Question 246

Bone tumor

• X-ray: • Nodular growth with endosteal scalloping and flocculent densities from calcification • Reactive thickened cortex bone • Grey-white glistening • Malignant cartilage +/- spotty calcifications • Prognosis: • Poor with large size and grade 3 • Metastasis: Lungs and bone

Answer 246

CONVENTIONAL CHONDROSARCOMA

Question 247

Types of chondrosarcoma

1. Conventional gone bad
2. Teens/young adults. EPIPHYSIS. Outlier
3. Teens/Young adults

Answer 247

1. DEDIFFERENTIATED** • Low-grade chondrosarcoma and high grade sarcoma
2. CLEAR CELL CHONDROSARCOMA** • Teens/young adults • Epiphysis
3. MESENCHYMAL CHONDROSARCOMA • Teens/young adults

Question 248

Differentiate fibrous cortical defect vs nonossifying fibroma Age? Presents? Location? Size? Course?

Answer 248

1. Fibrous cortical defect Age; 40% children Presents; incidental Location; Metaphysis/cortex knee Size ; small (<0.5cm) Course; resolve into normal bone
2. Nonossifying fibroma Age; adolescent Presents; incidental or pathologic fracture Location; Metaphysis/cortex knee Size; large (up to 6cm) Course; persists (probably prior fibrous cortical defect)

Question 249

Bone tumor

• Three patterns: A. Monostotic B. Polyostotic with soft tissue myxomas C. Polyostotic with endocrine dysfunction (McCune-Albright Syndrome) • X-ray: Ground glass and well-demarcated border • Metaphysis or diaphysis

Answer 249

FIBROUS DYSPLASIA

Question 250

Define the 3 types of fibrous dysplasia

Answer 250

1. Monostotic • 70% • Teens; stops growth with growth plate closure • Ribs, femur, tibia, jaws, calvaria and humerus • Incidental in most cases; can be deform bone
2. Polyostotic • Mazabraud Syndrome: Soft tissue myxomas • McCune-Albright Syndrome
3. McCune-Albright Syndrome • Café au lait skin pigmentations • Endocrine: - Sexual precocity (often presenting); 5 year old with puberty sign - Hyperthyroidism, pituitary adenomas with GH, primary adrenal hyperplasia • Hyperactive G-protein of GNAS gene

Question 251

Identify bone tumor based on presentation

• Well-circumscribed intramedullary • Large may expand and distort bone • Gross: Tan-white and gritty • Microscopic: Chinese character woven bone in fibrous stroma • Small increased risk to become malignant - Increased in polyostotic - Increased if irradiated ***CHINESE CHARACTER

Answer 251

FIBROUS DYSPLASIA

Question 252

IDENTIFY BONE TUMOR

• 80% less than 20 years; 6-10% primary bone tumors • Small round (blue) cell tumor of bone and soft tissue - Glycogen - Homer-Wright rosettes • EWS gene translocation; • Most often t(11;22) EWS-FLI1****

Answer 252

EWING SARCOMA AND PRIMITIVE NEUROECTODERMAL TUMOR (PNET)

Distinction based on degree of neural differentiation

****Most often t(11;22) EWS-FLI1****

Question 253

BONE TUMOR

• Medullary cavity but invade the cortex into soft tissue to create a mass • Most often diaphysis of long tubular bones (femur) and flat bones of pelvis • May have fever, anemia, leukocytosis • X-ray: lytic destruction with onionskin periosteal reaction and sunburst pattern • 75% five-year survival

Answer 253

ES/PNET **EWING SARCOMA

**glycogen stains red in PAS

Question 254

Identify bone tumor

Answer 254

Giant cell tumor

• X-ray: Lytic excentric eroding into subchoroidal bone plate
• May erode cortex into soft tissue with a thin shell of covering bone
• Curettage: Half recur
• 4% metastasize to lung

Question 255

identify bone tumor

Answer 255

Giant cell tumor of bone

• Benign locally aggressive tumor of macrophage/monocyte system
• Giant cells (can have 100+ nuclei)
• Mononuclear cells express RANKL
• Hemorrhage, reactive bone, hemosiderin

Question 256

Identify bone tumor

A. Benign locally aggressive tumor of macrophage/monocyte system

• Giant cells (can have 100+ nuclei)
• Mononuclear cells express RANKL
• Hemorrhage, reactive bone, hemosiderin

B. Epiphyses but may extend into metaphysis

C. Most common: Knee

Answer 256

Giant cell tumor of bone; Red brown tumor. Often cystic degeneration. Uniform oval mononuclear cells expressing RANKL. Multinucleated osteoclast-like giant cells (can have over 100 nuclei but all nuclei have same morphology and mononuclear cells). Hemorrhage, reactive bone, hemosiderin. Adolescents: Metaphysis (limited by physis)

Question 257

Bone Condition

Multiloculated blood-filled cysts

Rapid growth may appear malignant

< 20 years

Metaphysis of long bones and posterior vertebrae

Most often pain and swelling

Rare recurrence rate

Answer 257

ABC; ANEURYSMAL BONE CYST

• X-ray: Eccentric, expansile and well-demarcated
• Histology:
• Blood filled cysts separated by internal septae (can see on CT or MRI)
• Fibroblasts and multinucleated giant cells
• Woven bone
• 1/3 have cartilage-like matrix (“blue bone”)

Question 258

• MOST COMMON FORM OF SKELETAL MALIGNANCY
• Pathway of spread
• Direct extension
• Lymphatic or hematogenous
• Intraspinal seeding (Batson plexus of veins)

•May be lytic, sclerotic, or mixed

**Differentiate condition in adults vs kids

Answer 258

Metastatic disease

Adult metastatic disease; 75% are fromv•Prostate: usually a sclerotic bone response •Breast •Kidney •Lung •“BLT and a Kosher Pickle” breast, lung, thyroid, kidney, prostate

•Most often in axial skeleton

Examples; 1) osteoblastic metastases in the vertebral column in pt with a metastatic adenocarcinoma of prostate. 2) Metastatic carcinoma, lytic lesion. 3) Bone metastases breast ductal carcinoma

Pediatric metastatic disease; •Neuroblastoma •Wilms tumor •Osteosarcoma •Ewing sarcoma •Rhabdomyosarcoma

Question 259

identify type of metastatic disease in adult population

Answer 259

Vertebrae with lytic metastases

Because there are multiple areas where the bone appears to be replaced by yellow-white tissue, one should think of metastatic tumor. The collapse of one vertebra and the apparent dissolution of the right lateral aspect of another suggests strongly that these and other lesions are osteolytic. About 50% of the bone must be lysed before a lesion can be seen radiographically in the patient.