Exam 1 Week 1 Flashcards

Question

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

Answer 1

• 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%

Answer 2

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

Answer 3

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

Answer 4

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

Answer 5

Dermatosis Papulosa Nigra

Answer 6

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

Answer 7

Diabetes mellitus

Answer 8

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

Answer 9

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\*\*

Answer 10

• 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

Answer 11

Actinic keratosis \*\* Squamous cell carcinoma

Answer 12

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

Answer 13

• 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

Answer 14

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

Answer 15

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

Answer 16

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

Answer 17

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

Answer 18

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

Answer 19

• 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

Answer 20

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

Answer 21

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

Answer 22

• 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

Answer 23

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

Answer 24

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\*

Answer 25

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

Answer 26

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

Answer 27

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

Answer 28

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)

Answer 29

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

Answer 30

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

Answer 31

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

Answer 32

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

Answer 33

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

Answer 34

Dermatofibrosarcoma protuberans \*\*tumor of dermis

Answer 35

Dermatofibrosarcoma protuberans (DFSP) CD34+

Answer 36

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

Answer 37

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

Answer 38

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

Answer 39

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

Answer 40

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

Answer 41

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\*

Answer 42

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

Answer 43

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.

Answer 44

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

Answer 45

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.

Answer 46

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

Answer 47

Nummular dermatitis

Answer 48

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

Answer 49

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

Answer 50

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

Answer 51

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

Answer 52

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

Answer 53

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)

Answer 54

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

Answer 55

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

Answer 56

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.

Answer 57

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

Answer 58

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

Answer 59

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

Answer 60

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.

Answer 61

Staphylococcal Scalded Skin Syndrome (Ritter’s disease)

Answer 62

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.

Answer 63

Erysipelas \*\*It is always caused by GAS

Answer 64

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

Answer 65

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

Answer 66

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

Answer 67

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

Answer 68

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

Answer 69

Ecthyma Ecthyma gangrenosa from P. aeruginosa bacteremia in neutropenic patients

Answer 70

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.

Answer 71

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

Answer 72

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

Answer 73

Necrotizing fasciitis caused by V. vulnificus

Answer 74

Necrotizing infection of muscle: myonecrosis

Answer 75

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.

Answer 76

• 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

Answer 77

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.

Answer 78

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

Answer 79

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

Answer 80

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

Answer 81

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

Answer 82

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

Answer 83

Vasculitis

Answer 84

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)

Answer 85

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

Answer 86

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

Answer 87

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

Answer 88

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)

Answer 89

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

Answer 90

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

Answer 91

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

Answer 92

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%

Answer 93

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

Answer 94

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

Answer 95

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

Answer 96

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

Answer 97

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)

Answer 98

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

Answer 99

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)

Answer 100

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

Answer 101

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

Answer 102

Eczematous Contact Dermatitis \*\*Zinc ointment

Answer 103

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

Answer 104

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

Answer 105

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

Answer 106

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

Answer 107

EOSINOPHILIA

Answer 108

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

Answer 109

HEMOLYTIC ANEMIA

Answer 110

THROMBOCYTOPENIA

Answer 111

Agranulocytosis

Answer 112

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

Answer 113

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

Answer 114

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%.

Answer 115

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

Answer 116

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

Answer 117

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

Answer 118

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

Answer 119

• 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

Answer 120

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)

Answer 121

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.

Answer 122

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

Answer 123

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

Answer 124

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)

Answer 125

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

Answer 126

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

Answer 127

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

Answer 128

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

Answer 129

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

Answer 130

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

Answer 131

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

Answer 132

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

Answer 133

Acne vulgaris

Answer 134

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

Answer 135

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

Answer 136

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

Answer 137

PANNICULITIS

Answer 138

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

Answer 139

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.

Answer 140

Verruca vulgaris

Answer 141

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.

Answer 142

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)

Answer 143

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

Answer 144

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.

Answer 145

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

Answer 146

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.

Answer 147

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

Answer 148

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

Answer 149

• 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)

Answer 150

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

Answer 151

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)

Answer 152

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

Answer 153

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

Answer 154

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

Answer 155

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

Answer 156

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

Answer 157

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)

Answer 158

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.

Answer 159

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)

Answer 160

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

Answer 161

**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

Answer 162

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)

Answer 163

\*\* 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

Answer 164

**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

Answer 165

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

Answer 166

**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) ```

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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)

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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.

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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)

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SPOROTRICHOSIS

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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)

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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

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* 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)

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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

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1. Wooven bone 2. Lamellar bone

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BONE FORMATION: Intramembranous ossification * Direct from mesenchyme * Appositional growth LOCATION LOCATION LOCATION * Epiphysis: Distal to growth plate * Metaphysis: Beneath growth plate * Diaphysis: Center

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1. Dysostosis 2. Dysplasia \*\*6 fingers or branchydactyly; HOXD13 defect

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CLEIDOCRANIAL DYSPLASIA \*\*no collar bones

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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

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THANATOPHORIC DWARFISM type 1 - bowed femur type 2 - cloverleaf skull

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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

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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

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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

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OSTEOPOROSIS \*\*X-ray is a poor test to detect * Osteopenia: Decrease bone mass * Osteoporosis: Osteopenia to the point of risk of fracture

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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

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SENILE OSTEOPOROSIS “low turnover variant”

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

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

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* 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,

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

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

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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

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RENAL OSTEODYSTROPHY

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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

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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)

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

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

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

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OSTEONECROSIS (AVASCULAR NECROSIS)

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AVASCULAR NECROSIS

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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

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

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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

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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

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* 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

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TB OSTEOMYELITIS

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

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

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• 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

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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

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

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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

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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

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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

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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

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• 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

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OSTEOCHONDROMA “EXOSTOSIS”

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OSTEOCHONDROMA

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CHONRDROMA

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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

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CHONDROBLASTOMA

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• 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

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CONVENTIONAL CHONDROSARCOMA

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

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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)

Answer 226

FIBROUS DYSPLASIA

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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

Answer 228

FIBROUS DYSPLASIA

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EWING SARCOMA AND PRIMITIVE NEUROECTODERMAL TUMOR (PNET) Distinction based on degree of neural differentiation \*\*\*\*Most often t(11;22) EWS-FLI1\*\*\*\*

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ES/PNET \*\*EWING SARCOMA \*\*glycogen stains red in PAS

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**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

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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

Answer 233

**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)

Answer 234

**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”)

Answer 235

**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

Answer 236

**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.

Exam 1 Week 1 Flashcards

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