week11

Herpes Zoster:

(Shingles) Generally limited to the area of skin innervated by a single sensory ganglion, occurs in a pattern that reflects the interneural spread of the reactivated virus. Pain may precede the rash and may continue after the rash goes away (postherpetec nerualgia)

Know the 5 strata of the epidermis.

-Stratum Corneum -Stratum Lucidum- only present in thicker skin -Stratum Granulosum -Stratum Spinosum (Stratum of Malpighi) -Stratum Basale (Stratum of Malpighi)

-abnormal keratinization

...

-abnormal shedding

...

macular or papular lesions

...

Clinical Features of Psoriasis:

2% of population. Onset peaks in adolescence and at age 60 NEED TO BE ABLE TO RECOGNIZE IT Well demarcated Salmon colored plaques Silver white scale Elpbows, knees, scalp, lumboscaral areas, interglueal celfts, and glans penis. Koebner phenomneon: lesions can be induced by local trauma (Seen in psoriasis and some other disorders) Pinpoint bleeding: auspitz sign Can present as total body erythema and scaling, nail changes in 30% of cases Yellow brown discoloration Thickening crumbling Onycolysis: separation of nail form bed Pitting or dimpling

Rocky Mountain Spotted Fever

20-30% mortality Presentation 2-14 days after exposure (initially blanching-->nonblanching, macular -->papular-->ecchymosis, sudden fever, myalgias, rash), clinical diagnosis, treat, THEN confirm, necrotizing vasculitis that leads to blood into tissues and necrosis. Treat with Doxycycline (children or adults)

Chronic Renal Disease and Cholestasis

25-85% of patients with renal failure suffer distressing itch. K-opioid agonists were antipruritic, k-opioid antagonists induced pruritus. It is believed that pain inhibits itch whereas inhibition of pain can cause itch.

Clinical Features of seborrheic dermatitis:

3-5% of population (commonly associated with Parkinson's disease and AIDS Areas with high density of sebaceous glands (scalp, forehead, external auditory canal, retroauricular area, nasolabial folds, presternal area) Dandruff in scalp, cradle cap in infants Macules and papules on an erythematous-yellow, greast base with extensive scaling and crusting

Staphylococcus Aureus Toxins:

5 Cytolytic: α,β,δ,γ, P-V leukocidin α: lyses cells by creating pores distrupting muscle tissue, blood vessels, lyses erythrocytres, hepatocyres, and platelets β: catalyses the hydrolysis of phingomyelin and lysophosphatidylcholine as a ersult it distrupts membranes and causes lysis δ: it acts as a surfucant to distrupt membranes γ & P-V leukocidin: is a pore forming toxin (rare in hospital aquired MRSA but found in 100% of of community aquired MRSA) 2 exfoliative: A and B. Exfoliative toxins are serine proteases that split desmoglein, which is one of a series of proteins required for holding cells together in the stratum granulosum of keratinized epidermis. As a result, there is severe blistering then exfoliation. The degree of exfolation depends on the degree of dissemination. 8 Enterotoxins: A-E, G, H,I 1 Toxic Shock Syndrome Toxin: TSST-1 Exfoliative Toxin A, the enterotoxins and TSST-1: act as superantigens, causint cytokine storm, hypotension, shock, and fever.

Clinical Features of lichen planus:

6 P's: Pruritic, Purple, Polygonal, Planar, Papules, Plaques Wrists, elbows, shins, ankles, glans penis. Fine white reticular pattern on surface called Wickham striae Oral lesions: seen in about 70% of cases present as white reticulated lesions Koebner Phenomenon: lesions develop in areas of scratching or trauma (not specific to any one disease) 10% have nail changes

Psoriasis

80% of patients with Psoriasis report itch. Itch caused by psoriasis can be classified as either pruriceptive or neuropathic.

Vaccinia:

????????????

2 exfoliative

A and B. Exfoliative toxins are serine proteases that split desmoglein, which is one of a series of proteins required for holding cells together in the stratum granulosum of keratinized epidermis. As a result, there is severe blistering then exfoliation. The degree of exfolation depends on the degree of dissemination.

8 Enterotoxins

A-E, G, H,I

Morphology of pemphigus foliaceus :

Acantholysis selectively involves the cells at the layer of the stratum granulosum leading to SUBCORNEAL BLISTERS

Tick Borne Typhus:

An inoculation eschar: Tache noire- crusted erosion with surrounding erythema on the left hip area. The rash begins on the trunk and spreads to the extremity's, unlike the rash seen in Rocky Mountain Spotted Fever. General Symptoms: headache, fever, chills, myalgia, arthralgias, malaise, anorexia, endemic to africa. Incubation period: Range 3-14 days Prodrome: nonspecific Travel history: Africa Onset sudden in 50% of patients Rash: about 3-4 days after appearance of tache noire, an erythematous maculopapular eruption appears on trunk, may subsequently disseminate involving face, extremities, palms/soles. Density of eruption heightens during next few days. In severe cases lesions may become hemorrhagic.

· Outline the role of opioid peptides and potentially other excitatory factors in the generation of neurogenic itch/pruritus in systemic diseases such as renal failure, liver disease and HIV infection

Atopic Eczema: an itch scratch signal exists in atopic patients in which scratch damage enhances itch. Alloknesis is a prominent feature of the itch of atopic eczema. Sedative antihistamines are effective, low-sedation antihistamines are not usually effective. Suggest histamine is not a major peripheral mediator of atopic eczema. Opiod peptides might serve as central mediators since opioid antagonists are effective in some patients. Nocturnal scratching is a moajor problem especially in sleep stages 1 and 2 (superficial sleep) and occupies 10-20% of sleeping time leading to tiredness and irritability. First concern is treating dryness and infection. Although itch is a common and important symptom of systemic disease, it is often difficult to control due to its multiple components. Chronic Renal Disease and Cholestasis: 25-85% of patients with renal failure suffer distressing itch. K-opioid agonists were antipruritic, k-opioid antagonists induced pruritus. It is believed that pain inhibits itch whereas inhibition of pain can cause itch. HIV: itch can be an early sign of HIV. Mechanism of itch in HIV is not clear. Some evidence suggests HIV-1 coat protein gp120 has excitatory effect on nociceptive neurons. Neuropathic Itch: postherpetic neuralgia is one of the most common causes of neuropathic itch. Can occur simultaneously with pain. Often sign of MS. Most distinctive features are a paroxysmal (sudden attack) abrupt onset of itch and duration from seconds to minutes. Often awaken patient from sleep. Similar to Lhermittes's sign (electric sensation that runs down the back and into the limbs ofen elicited by bending the head forward). Impaired synaptic conductivity rather than demyelination might be responsible for these symptoms. Psoriasis: 80% of patients with Psoriasis report itch. Itch caused by psoriasis can be classified as either pruriceptive or neuropathic.

Cutaneous anthrax:

Black eschar surrounded by edema and purple vesicles, painless. About 20% of untreated cases of anthrax results in death, 80% are self-limiting and resolve without scarring Pain in cutaneous anthrax usually indicates streptococcal or staphylococcal superinfection 10% of cases of cutaneous anthrax progress to systemic anthrax Malignant edema is a rare complication usually involving the head and nick and manifested by severe edema, induration, multiple bullae, and shock. Inhalation anthrax: almost always fatal. First symptoms are fever, fatigue, malaise, cough, chest pain. High fever, rapid pulse, severe difficulty breathing follow in 2-5 days. Treatment is ciprofloxacin or doxycycline

Lyme Microorganism

Borrelia Burgdorferi Spirochete, doesn't stain well Transmission by ixodes tick bite (usually has to feed for more than 18 hours to infect you)

· Describe the pathogenesis, clinical features, and morphology of mycosis fungoides and Sezary syndrome

Both are Cutaneous T-Cell Lymphomas Both occur in adults 40-60 yrs of age, only difference, clinical manifestations, look the same under the microscope Pathogenesis: Malignant neoplasms (tumors) of CD4 T Helper cells. Will also often express abnomal cell surface antigens as well as have clonal T-Cell receptor gene rearrangements Morphology: Sezary Lutzner cells are the histologic landmarkwith markedly folded nuclear membranes which impart a hyperconvoluted or "Cerebriform" (buzzword) shape. Band-like infiltrate of Sezary lUtzner cells in dermis. Invasion of Sezary Lutzner Cells into Episermis as single cells and small clusters . Paurtrier microabscesses-buzzword

· Describe the clinical features, pathogenesis, and morphology of erythema nodosum and erythema induratum

Both are forms of panniculitis, more common in young women, tend to affect lower legs erythema nodosum

Erythrasma

Casued by Corynebacterium Minutissimum (gram+ diptheroid-club shaped, non-spore forming, aerobic or facultatively anaerobic bacillus.Predisposing factors- humid cutaneous microclimate: wamr and/or humid climate or season; occlusive clothing.shoes; obesity, hyperhidrosis. Clinical Manifestations- usually asymptomatic Skin lesion characteristics:patches, sharply marginated, wood lamp examination shows bright coral red differentiating erythrasma from similar appearing rashes (interingo). C. Minutissimim produces porphyrins that fluoresce coral red. KOH preparation was neg. for hyphae.

Pathogenesis of bullous pemphigoid:

Caused by IgG autoantibodies against hemidesmosome protein (BPAG2). IgG autoantibodies fix complement and cause tissue injury by recuriting eosinophils and neutrophils. Immunofluorescence shoes linear deposition of IgG and complement along the basement membrane

Haemophilus influenzae

Cellulitis involving the face, neck or upper extremities occassionaly occurs with bacteremic H. influenzae type B. Commonly described as having a peculiar purple-red or blue-red hue but is often indistinguishable from cellulitis caused by strep or staph.

· Know the clinical features and morphology of rosacea

Clinical Features: flusing episodes (triggers include sun exposure, emotional stress, cold/hot wheather, alcohol, spicy foods, exercise, wind, cosmetics, hot drinks), persistent erythems and telangiectasia, pustules and papules, Phinophyma (permanent thickineing of the nsal skin) Morphology: Perifollicular infiltrate composed of lymphocytes surrounded by dermal edema. There is also telangiectasia (spider veins) Pustular phase: neutrophils may occupy the follicles, follicular rupture may cause a granulomatous dermal reaction. Rhinophyma (red nose?) is associated with hypertrophy of sebaceous glands, follicular plugging by keratotic debris.

· Know the clinical features and morphology of acne vulgaris

Clinical Features: formation of comedomes, papules, pustules, nodules, and or cysts secondary to obstruction and inflammation foo the pilosebaceous units. Males tent ot have more severe disease. In adolescents it is thought to occur secondary to physiological hormonal changes and alterations of a hair follicles Especially the sebaceous glands). Can be exacerbated by drugs, occupational contacts, heavy clothing, cosmetics, tropical environments. Following types (which can coexist) Non-inflammatory Open comedones: small follicular papules that contain a central black keratin plug. The black plug is secondary to oxidation of melanin pigment Closed comedone: follicular papules that do not have avisible sentral plug. Since the keratin plug is trapped under the surface theses lesions are vulnerable to follicular rupture and inflammation Inflammatory Erythematous papules, nodules, and pustules Acne conglobata is the most severe form of acne vulgaris with sinus tract formation and scarring. The back and chest can be severely involved. Morphology: Open of closed comedones, papules, pustules, or deep inflammatory nodules can be seen depending on the stage of the disease. Open comedones (large orifices). Lymphohistiocytic infiltrates around affected follicles. Acute and chronic inflammation with follicular rupture. Dermal Abscess can be seen. Scarring may result.

· Describe the neural pathway for itch and its relationship to the neural pathway for pain from the skin to the cerebral cortex

Depending on which receptors are expressed in free nerve endings, sensory neurons can react to painful stimuli, mild touch, heat/cold, or itch Nocioceptors-pain Pruriceptors-itch Pain and itch receptors appear to belong to the same class Different proteins that the free nerve ending express detect different stimuli Both pain and itch travel via the spin thalamic tract suggesting that itch and pain get segregated before they reach STT neurons. WHY? When nocioceptors are activated they inhibit interneurons associated with the itch pathwway thus inhibiting the itch pathway? Because activating nocioreceptors (pain) inhibits itch pathway, this is why scratching (pain) alleviates itch Internurons in the Spinothalamic pathway express different types of morphine receptors. Morphine increases activation of pruriceptive (itch) interneurons and decreases activity of nociceptive (pain) interneurons. This is why morphine induces itch and alleviates pain. Itch is transmitted by C neurons (unmyelinated) which are distinct from the polymodal nociceptors that are implicated in pain processing. Itch neurons can be identified by their lasting response to histamine application, and are characterized by their slow conduction velocities and extensive terminal branching. Itch activates the anterior cingulate cortex, supplementary motor area, and inferior parietal lobe with a left hemisphere predominance. The substantial coactivation of the motor area suggests that itch is inherently linked to a desire to scratch. Pattern of activation is very similar to that of the pain sensation. Subtle differences have been noted though. Scratching and rubbing the skin inhibits itch (surround inhibition) by stimulated myelinated A neurons via low threshold mechanoreceptors which excite presynaptic and postsynaptic mechanisms to inhibit neuronal circuits in the grey matter of the spinal cord and lead to temporary suppression of itching. Scratching also activates nociceptors inhibiting itch.

· Describe the viral causitive agents of roseola infantum [HHV6 and 7] in terms of genome architecture, virion morphology, clinical manifestations.

Double Stranded DNA Icosahedral Enveloped CD46, replicates in salivary glands, T-cell tropic, latent in monocytes/macrophages Transmission: nasopharyngeal viral shedding from healthy individuals Patient age: usually seen in children ages 6mos-4yrs. Disease: acute febrile illness (3d-7d) followed by rash

Wheal (hive)

Edematous plaque, transient, inflammatory response

Nodule

Elevated, solid, greater than 0.6 cm. Large nodule is a tumor

Herpesvirus Family

Enveloped, double stranded linear DNA virus Virulence is dependent on envelope glycoproteins Icosadeltahedral (162 capsomers) Capableof Lytic, Perisistent, and Latent/Recurrent Infections Family: HSV-1, HSV-2, VZV, EBV, CMV, HHV6, HHV7, HHV8

Morphology of lichen planus:

Epidermal thickening (Acanthosis) Hyperkeratosis Thickening of the granular cell layer (Hypergranulosis) Zigzag contour of the dermoepidermal interface (saw tooth appearance) Lymphocytic infiltrate along the dermoepidermal junction Degeneration and necrosis of the basal cell layer (colloid of Civatte bodies)

Morphology of Psoriasis: Epidermal thickening (acanthosis) with Elongation of rete ridges (test-tube like). Extensive overlying hyperkeratotic and parakeratotic scale. Lymphocytes and neutrophils within the superficial epidermal layers and collecting within the scale (Munro microabscesses).

Epidermal thickening (acanthosis) with Elongation of rete ridges (test-tube like). Extensive overlying hyperkeratotic and parakeratotic scale. Lymphocytes and neutrophils within the superficial epidermal layers and collecting within the scale (Munro microabscesses).

-Skin is made up of

Epidermis, Dermis, Subcutis (hypodermis) and Skin appendages)

Lyme Disease Clinical Presentation

Erythema Migrans: Target Rash General Symptoms: Stage 1: none Stage 2: Disseminated- fever, lymphadenopathy, neurologic involvement, cardiac, musculoskeletal Stage 3: persistent infection- chronic neruoborreliosis, arthritis

Erysipelas

Etiology- GAS Description- acute, spreading infections of dermal and subcutaneous tissues. A red, hot, tender area of skin. Often originateing at the site of arterial entry. Essentially the superficial form of cellulitis. Sharp demarcation and raised. Painful, well-defined, erythematous, edematous plaques often involving central face. On palpation the skin is hot and tender.

ecthyma gangrenosum

Etiology- Pseudomonas aeruginosa Gunmetal gray, painless, infarcted lesions with surrounding erythema. Lesion starts with an erythematous or purpuric macule and develops into a hemorrhagic bulla that ruptures; becomes gunmetal gray, black eschar and surrounding erythema; and evolves into a necrotic black or gray-black eschar and surrounding erythema. Frequently the lesion is in the anogenital or axillary region. Ecthyma gangrenosum usually occurs in immuno-compromised patients, burn victims, and in patients receiving long courses of antibiotic therapy

Ecthyma

Etiology- S. Aureus and GAS Infections of the Epidermis which extend into the dermis (ecthyma) Clinical findings- crusted deep erosion or ulcers, thick oyster shell like crust, duration (weeks to months), Symptoms (pain, tenderness) Portal of entry- secondary infections of preexisting dermatoses Predisposing Factors- lesion of neglect (develops in excoriations), insect bites, minor trauma in diabetics, elderly patients, soldiers, and alcoholics.

Organism likely Responsible for NF

Etiology: Generally Streptococcus Pyogenes GAS Gram + Cocci in chains Beta Hemolytic Catalase Neg. Lancefield A Bacitracin Sensitive (won't grow near disk)

RicketsialPox:

Etiology: R. akari, carried by a mice mite. In the first phase a papule develops at the site of thermites bite and quickly ulcerates and forms and eschar. Tache Noire: regional lymph nodes enlarged, 10-17 days after bite, non-specific symptoms of malaise, chills/fever, headache, myalgia, nausea/vomiting, abdominal pain, cough, conjunctivitis, photophobia may occur Rash: 2-6 days after onset of nonspecific symptoms, red macules and papules appear may evolve to characteristic vesicles (pox), crusted erosions occur; lesion heal without scarring. Fever resolves in 6-10 days without treatmetn with doxycycline.

Impetigo

Etiology: S. Aureus or GAS Clinical Manifestations: crusted Erosions, lasts days to weeks Skin Lesions Characteristics: small erosions with crust, golden-yellow crusts are often seen but are not pathognomonic, scattered discrete lesions, without therapy become confluent, satellite lesions occur by autoinoculation. Portal of entry: minor superficial breaks in the skin Age: more common in children

Morphology of dermatitis herpetiformis:

Fibrin and neutrophils accumulate at tips of dermal papillae to form microabsceses develop at the tips of dermal papillae. Inflammation causes focal dermoepidermal separations that coalesce to produce true subepidermal blisters.

Neural Crest Cells

Form Melanocytes and Merkel Cells. IN the head and neck, neural crest also forms much of the dermis.

Dermoscopy

Further evaluation, grossly of lesion, Apply ABCD specific to dermoscopy, training, device)

Describe cutaneous manifestations that may result as a feature of systemic infections N. gonorrhoeae

Gonococcemia- a mixture of pustules surrounded by a thin zone or purpura, macules papules, purpuric vesicle and bullae and purpuric infarcts.

· Recognize the organism most commonly responsible for "hot tube folliculitis" in addition to Web Space intertrigo, "Green Nail", and burn infections, Ecthyma gangrenosum based on shape, Gram stain, growth/metabolism, and biochemical tests. Pseudomonas aeruginosa: responsible for (hot tub folliculitis, webspace intertrigo, green nail, burn infections, and ecthyma gangrenosum)

Gram (-) Rods in Pairs and Singles Abundant capsule Non lactose fermenter Green and blue pigments Fruity smelling Growth Metabolism: Does Not Ferment Carbohydrates. Obligate aerobe Oxidase + Blood Agar (brown colonies, semi-clearing) MacConkey Agar (colorless colonies, lactose-non fermenting) Nutrient agar (blue-green colonies)

Staphylococcus Aureus Enzymes

Hyaluronidase, Staphylokinase, Lipase, Dnase, Coagulase

Explain the Function of the AIRE gene and its relationship to autoimmunity

IV. AIRE Gene: a transcription factor in the thymus (autoimmune regulator) a. FX: i. Responsible for thymic expression of otherwise peripherally-restricted protein antigens (self peptides) ii. AIRE mutations cause lapse in negative selection à leads to autoimmune disease 1. EX: Autoimmune Polyendocrine Syndrome (APSI)

· Describe the Papilloma virus family ( HPV) including the viral and genomic architecture/structure.

Icosahedral Capsid 50-55nm No envelope 2 structural proteins compose the capsid L1 and L2 Genome is Circular DNA Target Cell: Basal Keratinocyte's Viral replication proceeds along with epithelial cell differentiation into keratinocytes Transmission: skin breaks Replication in Squamous Epithelium: Mature virions shed, late capsid proteins L2 and L1, Viral DNA amplification, Virion assembly, Differentiation dependent genes E6 and E7, Primary Infection of Basal Cell layer through skin breaks. Immediate early proteins E1, E2, E5. HPV replication is controlled by the host cells transcriptional machinery as determined by the differentation of the skin of mucosa epithelium.

Pathogenesis of dermatitis herpetiformis:

IgA antibodies to dietary gluten Immunofluorescence discontinuous, granular deposits of IgA localized at tips of dermal papillae

Folliculitis

Infection of the hair folicule with or without pus in the ostium of follicle (most commonly caused by MSSA or MRSA Staph. Age of onset- children, adolescents, and young adults, more common in boys. Predisposing factors: chronic S. aureus carrier, diabetes, poor hygeine, bacericidal defects (chronic granulamotous disease), hyper IgE syndrome (Job Syndrome), HIV/AIDS, especially MRSA syndrome

· Describe in broad conceptual terms the effects of scratching and rubbing on the modulation of itch/pruritis

Itch: leads to scratch reflex Pain: leads to withdrawal reflex Stimulus causing itch leads to two distinct responses: first, localized itch that persists only seconds after stimulus is removed and second, a subsequent diffuse, poorly localized area surrounding the site which responds with intense itch when exposed to gentle touch or other minor stimuli. Sensation of itchy skin: alloknesis Scratching and rubbing the skin inhibits itch (surround inhibition) by stimulated myelinated A neurons via low threshold mechanoreceptors which excite presynaptic and postsynaptic mechanisms to inhibit neuronal circuits in the grey matter of the spinal cord and lead to temporary suppression of itching. Scratching also activates nociceptors inhibiting itch. Animal models are difficult because animals scratch frequently anyways but dose-related scratching has been observed (the more itch inducing injection they are given the more they scratch?)

Tolerance

Lack of response to self antigens

Bacillus Anthracis

Large Aerobic Spore-Forming Gram + Rod Non-hemolytic colonies with an irregular border Anti-phagocytic capsule Three plasmid-encoded proteins synergize to cause cell destruction: protective antigen (named for its role in the vaccine), edema factor (responsible for increased intracellular cAMP and severe edema) and Lethal Factor (causes tissue necrosis).

Leprosy Clinical Presentation

Leprosy mainly affects the skin and peripheral nerves Left untreated can lead to progressive and permanent damage of nerves leading to loss of sensation and sweating in the extremities and paralysis of muscles in the hands, feet and face. Armadillos may transmit it?

Varicella Zoster

Linear Double Stranded DNA Icosahedral, enveloped Capable of Lytic, Persistent, and Latent/Recurrent infection Replication: ??? Causes chickenpox and shingles.

Erosion

Loss of epidermis, usually superficial, heal without scarring

Morphology erythema induratum:

MORE INFLAMMATION IN FATTY TISSUE, not sub-cutis

Pathogenesis of seborrheic dermatitis:

Malassezia furfur may be cause in some cases

Pathogenesis of urticaria pigmentosa and mastocytosis:

Mast cell derived mediators (especially histamine) induce symptoms

· Describe the pathogenesis and clinical features of urticaria pigmentosa and mastocytosis

Matrocytosis: refers to a spectrum of rare disorders characterized by increased numbers of mast cells in the skin or other otgans

Describe cutaneous manifestations that may result as a feature of systemic infections N. meningitidis

Meningococcemia- Erythematous macules, petechia, purpura and echymoses located on the extremetis and trunk. Extensive fun mental gray, hemmoraghic necrotic patches can develop by confluence of petechial and purpuric lesions of fulfillment meningococcemia

Congenital

Mongolian Spot, blue-gray macular discoloration in infants. Most commonly on back, sacral regions. May be solitary or multiple. Melanocytes trapped in dermis. Benign. Resolves. Predisposition to Asian, and Native American, Hispanics.

Morphology of Pemphigus Vulgaris:

Most loss of cells above the basal layer so that is where blister forms (suprabasal blister). Intact layer of intact basal cells "tombstones."

Leprosy Microorganism

Mycobacterium Leprae Gram + Acid Fast Bacillus (Rod) Transmitted by air trough droplets from nose and mouth during close and frequent contacts with untreated cases (one of the least infectious diseases due to the adequate natural immunity and infectious cases are rendered non-infectious within one week)

NF Clinical Presentation

NF defined as deep, rapidly progressing infection involving subcutaneous tissue and fascia. The disease progresses rapidly with a change from erythema, pain, edema to a central dusky violaceous discoloration with cutaneous anesthesia and hemorrhagic blisters 36 hours from onset. Severe constant pain, necrosis, crepitus, edema extending beyond the erythema, rapid spread despite antibiotics, woody hard feel and systemic toxicity, manifested by fever, leukocytosis, change in mental status and renal failure. Often begins at site of non-penetrating minor trauma. May develop at the site of a break in the epidermis. Most cases occur in otherwise healthy persons often in children and the elderly. Myonecrosis occurs concomitantly in 50% of NF cases. Fournier's gangrene is considered a form of NF however it is localized to the scrotum and perineal area. Spreads up the abdominal wall hence qualified as NF.

Neoplasm

Neoplasia literally means new growth Abnormal mass Growth exceeds and is uncoordinated with that of normal tissues Growth persists in the same excessive manner after cessation of the stimuli that evoked the change THE ENTIRE POPULATION OF CELLS WITHIN A NEOPLASM ARISES FROM A SINGLE CELL THAT HAS UNDERGONE GENETIC CHANGES (CLONAL) CAN BE BENIGN OR MALIGNANT

Pemphigus Vulgaris

No pruritis. Positive pain, skin and mucous membranes, target (desmoglein 3, blisters rupture easily, nikolsky sign

Molluscum Contagiosum:

Nodular to wart like lesions that resolve spontaneously after 6m in healthy people. Occurs on exposed skin of children and some sexually active adults in the general area. Without aggressive therapy in advanced HIV/AIDS, Mollusca enlarge; spontaneous regression does not occur. Molluscum Contagious is a self-limited epidermal viral infection. Risk groups (children, sexually active adults, immunocompromised [HIV/AIDS, organ transplant recipients]). Clinical manifestations: skin colored papules; often umbilicated, few to myriads of lesions, HIV/AIDS: large nodules, confluent. Course: resolve spontaneously in healthy people, can become confluent if not treated aggressively in HIV patients.

Morphology of erythema nodosum:

Notice that we are DEEP in the tissue (sub-cutis, deep down, adipose tissue) these are all cues that we are talking about Erythema Nodosum

Pathogenesis of pemphigus foliaceus:

Only targets Dsg1 so immunofluorescence shows deposito nof intercellular IgG deposits in the mores superficial layers of the epidermis (no fish net)

Pustule

Palpable lesion filled with purulent fluid (pus), usually less than 0.5 cm

· Know the pathogenesis, clinical features, and morphology of urticaria (AKA hives/allergic reaction)

Pathogenesis: IgE dependent: represents most cases, is due to the antigen induced release of vasoactive mediators from mast cells that have been sensitized with specific IgE antibodies. Etiologies include various antigens including food, pollens, drugs and insect venom. IgE independent: this is due to various substances that can directly degranulate mast cells. This includes medications (opiates are one example) as well as radiographic contrast media) Complement mediated: this is seen with hereditary angioneurotic edema. Inherited deficiency of C1 inhibitor. Clinical Features: increased dermal microvascular permeability that is secondary to localized mast cell degranulation. Results in wheals (hives- pruritic and edematous plaques). Angioedema refers to edema that occurs deeper involving the dermis and subcutaneous fat. Individual lesions will develop and fade within hours. Common sites include extreme ties (exposed to pressure). Persistent episodes may be associated with an underlying disorder such as collagen vascular disease. Morphology: Usually perivenular infiltrate. Mononuclear cells Eosinophils can be seen Superficial Dermal edema, this can cause collagen bundle's to be widely spaced Dilatio of superficail lymphatic channels (this is secondary to increased absorption of edema fluid)

· Know the pathogenesis, clinical features, and morphology of acute eczematous dermatitis

Pathogenesis: Initial Events: antigens at the epidermal surface are taken up by Langerhans cells which then migrate via lymphatics to the draining lymph nodes. The antigens are procesed by the langerhans cell and presented to CD4+ cells. The CD4+ cells are activated and differentiate into memory and effector cells. Re-exposure to the antigen: the corresponding memory T cells travel teo the involved skin site and into the tissues (The T cells then secrete cytokines and chemokines that result in the recruitment of inflammatory cells). Developmental Stages of Eczema: A.Dermal edema and perivascular infiltrates. B.Epidermal spongiosis and microvesicle formation. C-E Note the Scale formation and progressive acanthosis (increasing thickness?) Clinical Features: red papulovesicular lesions that can ooze and become crusted. Prolonged disease results in acanthosis and hyperkeratosis that manifests clinicaly as raised scaling plaques. Can be classifed as (allergic contact dermatitis, atopic dermatitis, drug-related dermatitis, primary irritatnt dermatitis). Lesions can be vulnerable to bacterial superinfection which may manifest as a yellow crust. Morphology: Spongiosis: the edema enters the epidermsi and separates keratinocytes. Progressive accumulation can result in intraepidermal vesicles. Early Stages: superficial and perivascular infiltrates composed of lymphocytes, papillary dermal edema.

· Know the pathogenesis, clinical features, and morphology of erythema multiforme

Pathogenesis: Immunologically mediated epidermal cell injury. Epithelial cells are destroyed by CD*+ CTLs that migrate to the skin. The exact target antigen is unknown. Clinical Features: acute, self-limited, mucocutaneous disorder that is often mile, can affect individuals of any age, associated with infection, drugs, malignance's, collagen-vascular disorders. Skin Lesions are multiform and include (macules, papules, vesicles, bullae, target lesion), lesions can be widely distributed but there usually is symmetric involvement of the extremities. Morphology: Early Lesions: superficial perivascular, lymphocytic infiltrate, edema, interface dermatitis (accumulation of lymphocytes along the dermoepidermal junction. This is associated with destruction of the keratinocytes) Later Lesions: Migration of lymphocytes into the epidermis, zones of epidermal necrosis with blister formation, erosions due to epidermal sloughing. The clinical targoid lesions correspond histophathologically to central necrosis surrounded by inflammation.

· Know the pathogenesis, clinical features, and morphology of dermatophytoses

Pathogenesis: due to filamentous fungi involvint the following genera (trichophyton, epidermophyton, microsporum), these prganisms are keratinolytic. The different types of dermatophytoses are knowns as tineas or ringworm. Classified according to anatomic site or structure that is involved. Clinical Features: Morphology: histologic features of dermatophytoses are variable and depend on properties of organism, host response, amount of bacterial superinfection. Eczematous dermatitis with intraepidermal neutrophils may be seen, fungi are present in the cornified layer of the skin, hair or nails. Fungal walls are stained pink/red with PAS stain.

· Know the pathogenesis, clinical features, and morphology of ichthyosis

Pathogenesis: main abnormality is defective desquamation which results in the retention of abnormally formed scales Clinical Features: most ichthyoses will manifest at or around the time of birth. There is scaling and flaking of the skin ranging from annoying dryness to severe and disfiguring disease. Morphology: Accumulation of compacted stratum corneum with loss of the normal basket-weave pattern. Inflammation is mild to absent. The Stratum corneum is thick and compacted.

· Know the pathogenesis, clinical features, and morphology of verrucae (aka warts)

Pathogenesis: more than 150 types of papillomavirus have been identified, many of which can cause warts. Clinical variants can be associated with certain HPV subtypes. For example HPV16 is associated with in situ squamous cell carcinoma of the genitalia and with bowenoid papulosis. HPV infection occurs via inoculation of the virus into epidermis by way of defects in the skin. Clinical Features: common warts, flat warts, palmar and plantar warts, venereal wart Morphology: Epidermal hyperplasia, Koilocytosis (cytoplasmic vacuolization, involves the superficial epidermal layers, Halos of pallor surround infected nuclei), Eosinophilic intracytoplasmic keratin aggregates may be seen secondary to the viral cytopathic effect.

· Know the pathogenesis, clinical features, and morphology of tinea versicolor

Pathogenesis: superficial fungal infection caused by lipophilic yeast Malassexia furfur. Clinical Features: hypopigmented or hyperpigmented macules. The lesions may be raised and may have a fine scale. Mild pruritus may be seen in severe cases. Any part of the body can be involved but common sites include upper trunk, arms, chest, shoulders, face, and neck. Morphology: Clusters of spherical to oval thick walled yeast like cells that can be mixed with short and frequently branched hyphae that have a tendency to orient end toe end. The overall appearance has been likened to spaghetti and meatballs.

· Know the pathogenesis, clinical features, and morphology of impetigo

Pathogenesis: superficial skin infection with crusting or bullae caused by streptococci or staphylococci. Contagious, most frequently seen in children, spread easily in individuals in close contact. Can be primary (direct invasion of nomral skin) or secondary (infection occurring at sites of minor skin trauma) Clinical Features: Bullous impetigo: This is caused by S. Aureus. Similar to non-bullous impetigo except the vesicles enlarge to form bullae which burst with subsequent formation of the honey-colored crust. Non-Bullous impetigo: in industrialized nations this form is most commonly caused by s. aureus and less often by GAS. This form generally presents as clusters of vesicles or pustules that rupture and form a honey-colored crust over the lesion. Morphology: Accumulation of neutrophils beneath the stratum corneum. This will often result in a subcorneal pustule. Rupture of the pustules can result in crust formation.

· Know the pathogenesis, clinical features, and morphology of molluscum contagiosum

Pathogenesis: viral disease of the skin caused by a poxvirus. The causative virus is one of the largest viruses seen in nature. Transmission is by direct contact and spread occurs by autoinoculation. Clinical Features: Multiple lesions can appear on the skin and mucous membranes. There is a predilection fo the turnk and anogenital areas. Lesions are frim, pink to skin colored, umbilicated papules. Size is ~0.2-0.4cm but larger lesion can be seem. A white materail can e expressed from the central umbilication (microscopic examination of this may reveal molluscum bodies) Morphology: Cuplike verrucous epidermal hyperplasia. Molluscum bodies (Ellipsoid, homogenous, cytoplasmic inclusions located in the cells of the sratum granulosum andstratum corneum. These are large in size, up toe 35 micrometers, numerous virions are present in these structures)

pemphigus vulgaris Clinical Features:

Pemphigus Vulgaris: 80% of cases Superficial vesicles and bullae the RUPTURE EASULY POSITIVE NIKOLSKY SIGN: slight rubbing of area causes blister Life threatening (5-15% mortality, Lots of open skin is dangerous)

Propionibacterium Acnes

Pleomorphic (rod shaped or branched, singular, pairs or groups) Anaerobic (aerotolerant) Gram + Rods Found on the skin and in the GI tract Part of Normal flora of skin Can cause catheter and shunt infections The pathogenesis of acne involves impaction of the sebaceous gland followed by inflammation caused by the presence of P. acnes. The pustules of acne are composed of sebum, inflammatory cells such as neutrophils and lymphocytes, and the organism.

Four categories of itch

Pruritoceptive itch, Neuropathic itch, Neurogenic itch, Psychogenic itch

Pemphigus Foliaceus Clinical Features:

Rare, less severe form, endemic in Brazil. Scalp, face, chest, back. Mucous membranes rarely affected. Superficial vesicles and bullaethat rupture easily. Superficial erosions and zones of erythema and crusting. POSITIVE NIKOLSKY SIGN.

Clinical Features of dermatitis herpetiformis:

Rare, predominantly males, associated with celiac's, usually very itchy. Bilateral symmetric grouped, pruritic urticaria and vesicle's. Preferentially affects elbows, knees, upper back, and buttocks.

· Develop a diagnostic approach to identify skin lesions:

Rash, Congenital or Acquired lesions Skin Lesions can be Congenital and/or fixed, non-evolving Rashes (rapidly evolving dermatoses--widespread involvement and/or multiple lesions) Acquired and evolving discrete skin lesions/growths

Port-Wine Malformation

Red, irregular shape, dermatomal distribution, almost always unilateral, permanent, may be associated with Sturge Weber Syndrome

Rickettsia Rickettsii:

Rocky mountain spotted fever Incubation period: Range 3-14 days Prodrome: Fever/Chills, anorexia, nausea, vomiting, irritability, malaise, severe headache, myalgia History of Tick bite: 60% of cases Symptoms: onset is usually abrupt: fever, severe headache, myalgia, arthralgia, sudden shaking, photophobia, prostration, nausea, vomiting, abdominal pain, all within the first 2 days. Only 14% of patients have rash on first day. 49% by 3rd day. In 30% of cases rash appears on day 6 or after. In 13% of cases no rash detected. Skin lesions: initially: few small pink macules, temporal evolution of the rash is extremely helpful in the diagnosis American Dog Tick is usual carrier

Morphology of bullous pemphigoid:

SUBEPIDERMAL NONACANTHOLYITC BLISTERS. Eosinophils, lymphocytes, and some neutrophils within the blister and dermis.

alloknesis

Sensation of itchy skin

Papule

Solid palpable lesion less than 0.5 cm.

1 Toxic Shock Syndrome Toxin

TSST-1

Coagulase

The cell bound forum clumps Staphylococcal cells and the secreted form converts fibrinogen to fibrin to cause formation of a fibrin layer around the Staphylococci and causes clot formation. This protects the bacterial cells from phagocytosis.

· Know the structural organization and growth phases of the hair follicle.

The first type of hair of the human embryo is called lanugo and is thin and unpigmented. Lanugo is replaced by vellus before birth. Terminal hair replaces vellus, which remains in the hairless regions of the skin (for example, forehead). Hair follicles are tubular invaginations of the epidermis and consist of two parts: hair shaft and hair bulb. The hair shaft includes the medulla, cortex, and cuticle (the latter associated with the internal root sheath). The hair bulb is the expanded portion of the hair follicle. The hair follicle is surrounded by connective tissue (associated with the external root sheath, a downgrowth of the epidermis). The dermal papilla extends into the hair bulb. Hair is generated from the base of the hair bulb. The hair bulb has two layers: the matrix zone ( where all mitotic activity occurs) and the keratogenous zone (where hair cells undergo keratinization). Two structures associated with the hair follicle: the arrector pilli muscle (attached to the ollicular bulb and the sebaceous glands, with their excretory ducts connected to the lumen of the hair follicle. Growth phases of Hair: Anagen Phase- acitve growth of hair follicles ~3 years. Catagen Phase- slowing transition of growth ~3 weeks. Telogen phase- resting phase ~12 weeks

Toxic Epidermal Necrolysis:

This disorder results in diffuse necrosis and sloughing of cutaneous and mucosal surfaces. The degree of involvement result in potential complications of infection and fluid loss.

· Know the general organization of the skin circulatory system.

Three interconnected vascular networks in the skin, papillary/sub papillary plexus (runs along papillary layer of dermis), cutaneous plexus (boundary of the subcutis and reticular dermis layers), subcutaneous plexus. The primary function of the cascualr network is thermoregulation and the secondary function is nutrition of the skin and appendages.

Sezary Syndrome Clinical Features:

Usually presents as diffuse erythema and scaling of the entire body surface (erythroderma). Seeding of the blood by malignant T Cells (leukemia). Aggressive behavior with associated lymph node and visceral involvement (hepatosplenomegaly-enlargement of liver and spleen). Skin lesions rarely proceed to the tumor stage.

Objective #4: Explain the development of CD4+ regulatory T cells in the thymus and their role in peripheral tolerance

V. CD4+ Regulatory T cells a. Some CD4+ autoreactive T Cells do not undergo apoptosisà they develop into regulatory T cells (T regs) b. FX of T Regs: i. Inhibit immune responses, especially by inhibiting low affinity responses in the periphery 1. They do this by producing inhibitory CKs (cytokines) a. Location of development: i. Develop in the Thymus b. CD4+ & CD25+ i. CD25 aka IL2R-alpha chain ii. CD25 is required to convert IL-2R into its highest affinity form c. Cytokines: i. Dependent on IL-2 & TGF-beta for development & maintenance d. Transcription Factor Involved: Foxp3 i. Foxp3 necessary for development & fx of T Regs ii. Foxp3 mutation à X-linked polyendocrinopathy & enteropathy (IPEX) (autoimmune disease) e. Role in Peripheral Tolerance: i. T regs mediate one form of peripheral tolerance ii. T regs produce IL-10 & TGF-beta (inhibitory CKs) 1. IL-10 & TGF-beta: block lymphocyte and macrophage activation 2. Remember: They are also anti-inflammatory CKs iii. Suppress cell: cell contact f. Side notes from Dr. P: i. *Since regulatory T cells express high levels of CD25 (a chain of the IL-2 receptor), they may inhibit responses by binding IL-2 so that is not available to bind effector T cells, thereby limiting their proliferation. ii. Regulatory T cells also express CTLA-4 which may bind to B7 on antigen presenting cells (APCs), thereby blocking the ability of this B7 to bind to CD28 on T cells and activate them

Objective #6: Define anergy & explain the role of innate immunity and costimulation in preventing anergy

VI. Anergy: T cell inactivation a. Happens when T cells recognize MHC peptide on resting APCs & there is inadequate expression of costimulators (B7) b. Second signal is indicative of accompanying innate immune response is lacking c. T cells become "anergic" d. Anergic: unresponsive to the antigen BUT do not undergo apoptosis

Describe the role of CTLA-4 in Energy

VII. Peripheral Tolerance: Anergy a. Anergy occurs when: i. Lack of activating B7:CD28 interactions ii. Too many inhibitory B7:CTLA-4 interactions iii. PD-1 inhibitory interactions where BD-1 binds to PD-L 1. PD-Là a ligand 2. PD-L related to B7 b. B7:CD28 vs B7:CTLA-4 CTLA-4 has a higher affinity for B7

Objective #8: Explain the process of activation-induced death of T cells in peripheral tolerance

VIII. Peripheral Tolerance: Activation-Induced T Cell Death (AICD) a. Occurs when: inadequate costimulation (B7:CD28) b. If inadequate stimulation à peptide/MHC:TCR triggers T Cell apoptosis via Mechanism 1 & Mechanism 2 c. AICD is irreversible d. Anergy is reversible

Scale

White or gray color flakes of skin over a lesion from excessive stratum or corneum

Objective #10: Describe peripheral tolerance as it relates to B lymphocytes

X. Peripheral Tolerance a. Lacking help, T-dept. B cells become anergic i. Anergic: B cell unresponsive to antigen but is not apoptosed b. B cells leave lymph node follicles and can't re-enter à lack survival stimulus à apoptosis c. Inhibitory receptors on B cells may also be engaged and prevent activation

Objective #11: Describe the natural decline of an immune response including the role of antibody feedback

XI. Decline of Immune Responses a. All immune responses diminish, even desirable ones b. Memory cells persist, Effector cells do not a. Costimulatory B7:CD28 intrxns & IL-2 maintain T cell survival/prolif. During immune responses b. 1-2 weeks after infection is cleared from body, i. Dec. in activation stimuli ii. Lack of survival signals à B&T cells apoptose iii. However, memory cells live on! c. Remember: i. B cell activation can also be blocked by antibody feedback 1. Via FcyIIB with ITIM 2. When BCR binds antigen with IgG bound à activation blocked

Objective #12: Describe two principle factors that contribute to the development of autoimmunity

XII. Autoimmunity a. Two Key Factors: i. #1.) Inheritance of susceptibility of genes i. #2.) Environmental triggers 1. ex: infections

Objective #13: List 4 common EXs of HLA-linked autoimmune diseases and the associated MHC alleles

XIV. Autoimmunity: MHC Alleles a. Most autoimmune diseases are associated with > one gene and > one genetic loci b. Certain MHC alleles inc. risk for certain autoimmune diseases c. Alleles inefficient at presenting self antigens (defective negative selection) or stimulating T reg cell development (defective peripheral tolerance) HLA-B27- Ankylosing Spondylitis HLA-DR4- Type I Diabetes, Rheumatoid Arthritis, Pemphigus Vulgaris

Objective #14: Describe 3 ways infections may play a role in the development of autoimmunity

XV. Autoimmunity: Infections a. Infections can precede autoimmunity i. APCs activated at infection site may stimulate self-reactive T cells & break anergy 1. The bystander effect ii. Microbes may contain peptides/epitopes similar & cross reactive w/ self-antigens 1. Molecular micmicry iii. Tissues injured by infection may expose "sequestered" antigens, activating an immune response 1. These sequestered antigens are normally hidden from the immune system

Patch

a flat discolored skin lesion that is greater than 0.5 cm. Larger than a macule.

III. Central Tolerance/Neg. Selection in T Cells:

a. Location: Thymus!! i. T Cell progenitors made in bone marrow, but mature in Thymus b. Maturation Process: i. TCR beta & TCR alpha chains rearranged ii. T Cells express CD4 & CD8 c. Double positive T: i. cell must bind with MHC self peptide weaklyà Positive selection ii. Double-positive T Cell must NOT bind self MHC peptide strongly or will undergo Apoptosisà Negative Selection d. Double positive T Cell will lose CD4 or CD8, dependent upon which one was not used during selection process

II. Central Tolerance aka Negative Selection in B Cells:

a. Location: in the bone marrow (central lymphoid organ) b. Immature B cells that bind strongly to self antigens: i. Apoptosis ii. Will undergo Receptor editing 1. Reactivate RAG genes 2. Generate new light chain 3. Change specificity

Objective #9: Describe 3 features of antigens that influence the choice between T cell tolerance and activation

a. Location: lymphoid organs: central (generative) vs. peripheral lymph.organs b. Second signals: absence vs. presence of signal c. Exposure: long vs. short

4 Types of Hypersensitivity

a. Type I à Immediate, IgE mediated b. Type II à Antibody-mediated (not IgE) c. Type III à Immune-complex mediated (DISCOID LE) d. Type IV à Cell-mediated (ALOPECIA, PSORIASIS,NICKEL ALLERGY???) i. Damage caused by: 1. Macrophages activated by TH1/IFN-y à Delayed Type Hypersensitivity 2. CD8+ CTL à killing of infected cells via CTL

Blanching

able to remove the color (correlates with degree of inflammation)

i. Central tolerance (negative selection)

acquired when lymphocytes 1st encounter self antigens in central lymphoid organs 1. Central lymph. Organs (bone marrow & thymus)

ii. Peripheral Tolerance

acquired when mature lymphocytes encounter self antigens in peripheral tissues

Exfoliative Toxin A, the enterotoxins and TSST-1

act as superantigens, causint cytokine storm, hypotension, shock, and fever.

Furuncles

aka boil, large painful, raised nodules that have an underlying collection of dead and necrotic tissue. Acute, deep-seated, red, hot, tender nodule or abscess that evolves from a staphylococcal folliculitis. Age of onset: children, adolescents, and young adults, more common in boys. Predisposing factors: chronic S. aureus carrier, diabetes, poor hygeine, bacericidal defects (chronic granulamotous disease), hyper IgE syndrome (Job Syndrome), HIV/AIDS, especially MRSA syndrome

Eccrine sweat glands

aka merocrine sweat glands are simple coiled tubular glands. Their primary function is control of body temperature. The secretory portion consists of three cell types Basal clear cells- separated from each other by intercellular canaliculi (they secrete water and electrolytes) Apical Dark Cells- secrete glycoproteins Myoepithelial cells

Lipase

allows for survival in sebaceous areas of the body

Atopic Eczema

an itch scratch signal exists in atopic patients in which scratch damage enhances itch. Alloknesis is a prominent feature of the itch of atopic eczema. Sedative antihistamines are effective, low-sedation antihistamines are not usually effective. Suggest histamine is not a major peripheral mediator of atopic eczema. Opiod peptides might serve as central mediators since opioid antagonists are effective in some patients. Nocturnal scratching is a moajor problem especially in sleep stages 1 and 2 (superficial sleep) and occupies 10-20% of sleeping time leading to tiredness and irritability. First concern is treating dryness and infection.

Pathogenesis of Pemphigus Vulgaris:

antibodies disrupt intercellular adhesion. Dsg1 most prominent at superficial layers, Dsg3 most prominent at basement layer therefore immunofluorescence shows fish net pattern.

Primary lesions

are how they start

Secondary lesions

are what they turn into, other factors change appearance

Chickenpox:

begins with face and scalp and spreads rapidly to the trunk with relative sparing of the extremities. New lesions appear in successive crops but their distribution remains central with some progression to the extremities. Centripetal. Rose colored macules to papules, vesicle and pustules and crusts develop in 12 hours. Arise in crops of lesions.

Pseudocowpox:

called Milker's nodule (Parapox), natural host is the cow, transmission by direct inoculation into the skin from infected animals of fresh meat. Cause localized disease in healthy individuals. Incubation 4-7 days. Mild systemic symptoms such as transient low fever, lesions develop after incubation period. Lesions: one to several on hands and sometimes face, red and occasionally pyritic macules that become raised papules. These become papulovesicles target-like a red center surrounded by a white or gray ring and outer red halo. The lesions then develop into bluish or violaceous tender nodules. Some ulcerate or have a central depression which results in formation of eschars with crust (6-9 weeks to heal)

Staphylokinase

can dissolve clots

β

catalyses the hydrolysis of phingomyelin and lysophosphatidylcholine as a ersult it distrupts membranes and causes lysis

Exposures

chemical, occupational, contacts, geographical, daycare/school

Atopic Dermatitis

chronic, pruritic, starts in childhood, personal or family history (hay fever, asthma, very dry skin, eczema) diagnosis made when 3 or more of the major features and 3 or more of minor features

Petechiae

circumscribed (within limits) deposit of blood less than 0.5 cm in diameter

apocrine glands

coiled and occur in the axilla, circumanal region and mons pubis, their secretory activity starts at puberty and their secretion acquires a conspicuous odor after being modified by local bacteria. The secretory acini are larger than in eccrine sweat glands. The excretory duct opens into the hair follicle (instead of into the epidermis as in the eccrine sweat glands). Ceruminous glands in the external auditory meatus and glands of Moll of the margins of the eyelids are examples of apocrine sweat glands.

cellulitis

common infection of the skin and the soft tissues underneath the skin. Bacteria invade broken or normal skin and start to spread under the skin and into the soft tissues. Inflammation may cause swelling, redness, pain, and/or warmth. Most commonly Staph Aeurus or GAS but can be associated with other organisms. Has many fo the featurs of erysipelas but extends into the subcutaneous tissues. Differs in two ways from erysipelas: cellulites lesions are primarily not raised and demarcation from uninvolved skin is indistinct. Facial/preorbital cellulitis in children tends to be H. infulenzae.

Purpura

deposit of blood under skin greater than 0.5 cm.

Teeth

derive from ectoderm, pulp from mesoderm and ondontoblasts from neural crest cells. Thus enamel comes from ectodermand dentin from neural crest.

Crust

dried surface layer of exudate from a lesion that may be blood, serum or purulent.

Bullous Pemphigoid

elderly patients, pruritic papular tense bullae, IgG and C3 at BM of Biopsy. IgG autantibodies in serum.

Desmesomes:

epithelial cell-epithelial cell

Hemidesmisomes:

epithelial cells-basement membranes

Macule

flat discoloration

Ehrlichia:

flu like illness, high fever, headache, malaise and myalgias, rash occurs in 3-40% of cases, can cause rash in up to 60% of children but is reported in fewer than 30% of adults. Rash spares the face but may spread to the palms and soles. Type of rash called erytroderma may develop in some pateints and resembles a sunburn and consits of a reddening of the skin that may peal after several days. May also develop a reash that appears similar to RMSF Coxiella burnetti (Q fever): Usually asymptomatic or flu-like. 5% are hospitalized with pneumonia, hepatitis or prolonged fevers, presents as endocarditis on damaged heart valves. RASH????? Borrelia Rash: Target Shaped Rash (erythema migrans)

Vesicle

fluid filled palpable lesion, usually less than 0.5 cm, fluid may be clear, blood or serous (pale yellow)

Bulla

fluid filled palpable lesion, usually less than 0.5 cm, fluid may be clear, blood or serous (pale yellow). So what is the difference from a Vesicle? Bullas are bigger

Mesoderm

for most of the body, mesoderm forms the dermis. Mesoderm also forms the hypodermis, which consists of connective tissues including adipose tissue.

Ectoderm

forms the epidermis and all epithelia that invaginate from the epidermis. These epithelia include sweat glands, sebaceous glands, and hair follicles. In fact, the entire surface of our eyeballs, the lining of our eyelids, hair, nails, and parts of our teeth. Mammary glands also form from ectoderm.

Clinical Features of bullous pemphigoid:

generally effects elderly patients. With or without mucosal involvement. Preferentially affects inner thighs, flexor surfaces of forearms, axillae, groin, and lower abdomen. TENSE BULLAE filled with clear fluid that DO NOT RUPTURE EASILY. Oral lesions in 10-15% that usually appear after cutaneous lesions. NEGATIVE NIKOLSKY SIGN.

Sebaceous glands

holocrine simple saccular glands. The secretory portion is located in the dermis, the excretory duct opens into the neck of the hair follicle. Cells of the secretory portion (alveoli) contain small lipid droplets (sebum). Peripheral cells are stem cells, thin basement membrane encloses gland, large center sebaceous cell, sebum reduces water loss, lubricates skin, microbial barrier.

Variola (Small Pox): Prodrome: Enanthem: Exanthem: Two clinical forms:

humans are only known resevoir, disease process begins on close prolonged exposure to an infected individual. Portal of enyty is oropharyngeal or RT. Virus attaches to respiratory epithelal cells, travels to regional lymph nodes. Transient primary viremia with uptake of virus by macrophages where replication occurs. Spread to reticuloendothelial organs. Seceondary viremia which causes prodrome. Virus spreas to the skin and mucosa along with other organs and tissues. Prodrome: high fever (102.2-105.8), chills, myalgia's, severe headache, develop within 7-17 days of expsoure. Person is usually severely ill and bedridden during prodromal period which lasts 2-4 days. Children may develop seizures. Urticarial or morbilliform lesions during prodrome. Enanthem: red macules on the mouth, tongue, oropharynx that subsequently vesivulate and ulcerate, releasing high concentrations of transmissible virus particles Exanthem: erupts two to several days after onset of fever in a centrifugal pattern and simultaneous progression of lesions. Two clinical forms: -variola major (ordinary small pox and most common- mortality 15-40%) *Modified small pox- accelerated, doesn't cause death, vaccinated people *Flat small pox- macules barely raise (children and immuno compromised) *Hemorrhagic or fulminant- 100% fatal (equal in vaccinated and unvaccinated) *Variola Sine- no rash, just headache and conjunctivitis-48hrs (titer shows antibodies) -variola minor (mortality 1%)

Hyaluronidase

hydrolyses exracellular matrix

Dnase

hydrolyzes abscess material reducing viscosity so that the bacterial cell does not get trapped and eliminated

Seborrheic Dermatitis

infant and adolescent/adult, presentation (erythematous plaques, yellow greasy scales), location (face, glabella, brow), often worse during winter, treatment for adults (face/skin folds- topical ketoconazole BID, low potency steroid cream BID, Chest-low to medium potency steroid, Scalp-selenium sulfide, tar, ketoconazole shampoo) treatment for infants (baby oil with soft bristle brush, wash every other day to daily).

Scabies

infestation by mite, highly contagious by direct skin contact, scratching destroys burrows, secondary infection can complicate diagnostic picture

Acne

inflammation reaction of body's natural sebaceous gland production and propionibacterium acnes. Adolescence and early adulthood. Family trends. Inflammatory, noninflammitory. Locations tend to be more pronounced to areas of increased populations of sebaceous glands.

Timing

initial, age group

γ & P-V leukocidin

is a pore forming toxin (rare in hospital aquired MRSA but found in 100% of of community aquired MRSA)

δ

it acts as a surfucant to distrupt membranes

Neuropathic itch

itch because of disease located at any point along the afferent pathway. (e.g. post-herpes zoster neuropathy and MS itch)

Neuropathic itch:

itch because of disease located at any point along the afferent pathway. (e.g. post-herpes zoster neuropathy and MS itch) Neuropathic Itch: postherpetic neuralgia (pain after shingles) is one of the most common causes of neuropathic itch. Can occur simultaneously with pain. Often sign of MS. Most distinctive features are a paroxysmal (sudden attack) abrupt onset of itch and duration from seconds to minutes. Often awaken patient from sleep. Similar to Lhermittes's sign (electric sensation that runs down the back and into the limbs often elicited by bending the head forward). Impaired synaptic conductivity rather than demyelination might be responsible for these symptoms.

HIV

itch can be an early sign of HIV. Mechanism of itch in HIV is not clear. Some evidence suggests HIV-1 coat protein gp120 has excitatory effect on nociceptive neurons.

Psychogenic itch

itch caused by delusions (e.g. parisitophobia)

Pruritoceptive itch

itch originating in the skin due to inflammation, dryness or other skin damaged. Transmitted by C nerve fibers. (e.g. scabies, insect bite)

Neurogenic itch

itch that originates centrally but without evidence of neural patholgy such as the itch of cholestasis (condition where bile can't flow from liver to duodenum) which is due to the action of opioid neuropeptides on p-opioid receptors.

Lupus Erythematosis

large spectrum of disease that ranges from cutaneous disease to multiorgan systemic disease, mostly affects women. FH often strong. Presentation- skin (butterfly rash, erythematous papular, bullae, discoid plaques) Hair (loss-diffuse or alopecia(circular patches of hair loss)) Organs (joints>renal>pericarditis>pneumonitis>GI)

Stevens Johnson Syndrome:

lesions resemble those of erythema multiform but are likely to be generalized. Erosions are hemorrhagic lesions and typically involve the lips and oral mucosa. The conjunctiva, urethra, genital, and perianal areas may also be involved. Secondary infection may result in sepsis that may be life threatening.

Melanomas

life threatening malignancy, recognition (mole changes ABCDE (Assymetry, Borders, Color, Diameter, Evolving), Hutchinson's sign), Diagnosis (Dermascopy, biopsy, Treatment (Moh's)

Thrombotic Thrombocytopenic Purpura

life threatening, skin (macular purpura, petechial hemorrhage, pentad (thrombocytopenia, neurologic dysfunction, fever, microangiopathic hemolytic anemia, renal dysfunction), evaluation (blood studies, hemolytic studies, urine, Coomb's, CT head)

Bullous Impetigo

localized form of SSSS, bullous impetigo have localized blisters that are culture positive (different from systemic form)

Meissner

location- dermal papilla, function-rapidly adapting mechanoreceptors (shape and texture discrimination in fingers)

Pacinian

location- hypodermis and deep fascia tissue, function- deep pressure, vibration sensation

1) keratinocytes (predominant cell type in epidermis, derived from ectoderm)

location- located throughout epidermis??? function- barrier against pathogens, heat, UV, and water loss?

Ruffini corpuscles

location- present in skin and joint capsule, function-responds to stretching sensation (strain gauges)

4)Merkel cells (neural crest derived)

location-found in the stratum basale. function- intra-epidermal touch receptors. Mechanoreceptors linked to adjacent keratinocytes by sesmosomes.

3) Langerhans cells (bone-marrow derived dendritic cells)

location-present in spiny layer and also in upper dermis. function- antigen recognition and processing. Similar to melanocytes', Langherhans cells have dendritic processes in contact with keratinocytes through E-Cadherin. Langerhans cells have on their surface langerin, a transmembrane C-type lectin, a CD1a. Langerin participates in the uptake of antigens; CD1a mediatesthe presentation of nonpeptide antigens to T cells. A characteristic landmark of Langerhans cells is the Birbeck granule

2)melanocytes (neural-crest derived)

location-stratum basale function- produce melanin contained in melanosomes. Melanin is prodcued by oxidation of tyrosine DOPA (1.3.4-dihydroxyphenylalanine by tyrosinase) DOPA is transformed into melanin.

Ulcer

loss of epidermis, depressed surface, described by size, shape, border, depth, tissue changes, heal with scarring

α

lyses cells by creating pores distrupting muscle tissue, blood vessels, lyses erythrocytres, hepatocyres, and platelets

-Functions of the Skin

major water barrier, major thermo-regulator, protective, immune system first line of defense, sensory functions, endocrine functions

Mastocytosis (systemic process) Clinical Manifestation: with or without skin disease

most common in adults. Involvement of internals organs

Hemangioma of Infancy

most common tumor of infancy, females more common than males, localized abnormality that may proliferate, often grow with child and later regresses, Diagnosis (clinical), usually resolves spontaneously but may be treated with localized tx 0 propranalol, cryosurgery etc.

Urticaria Pigmentosa (localized lesions) Clinical Manifestation:

mostly kids, Most common presentation (50% of all cases), tan-brown to salmon-colored non-sclaing macules and papules most prominent on the trunk and extremeties. Usually resolves by puberty. Darrier Sign: scratching of lesions results in localized dermal edema, erythema, and pruritis due to mast cells that produce histamine causing vasodilation Dermatographism: stroking appartently normal skin with a pointed instrument results in edema Some patients have acute systemic symptoms to certain foods/drugs alcohols and some even have anaphylactic reaction to bee, hornet, or wasp stings.

Associated Symptoms

multi-organ, fever, pruritis/pain, neurologic

Pathogenesis of Psoriasis:

multifactorial with both genetic and environmental factors, strong association HLA-C. Cytokine release and TNF appear to be involved.

Band-like infiltrate of Sezary lUtzner cells in dermis.Sezary Lutzner cells are the histologic landmark with markedly folded nuclear membranes which impart a hyperconvoluted or "Cerebriform" (buzzword) shape

mycosis fungoides and Sezary syndrome

Invasion of Sezary Lutzner Cells into Episermis as single cells and small clusters . Paurtrier microabscesses-buzzword

mycosis fungoides and Sezary syndrome

Paurtrier microabscesses-buzzword

mycosis fungoides and Sezary syndrome

Tinea

named by location (capitis, pedis, corporis), erythematous scaling plaques, often with a central clearing, dermatophyte, treatment (topical antifungal, oral antifungal, antibiotic-superimposed)

Carbuncles

occur when furuncle coalesce and extend to the deeper subcutaneous tissue and is often associated with system spread via bacteremia causing fever and chills. Deeper infection composed of interconnecting abscesses usually arising in several contiguous hair follices. Age of onset:children, adolescents, and young adults, more common in boys. Predisposing factors: chronic S. aureus carrier, diabetes, poor hygeine, bacericidal defects (chronic granulamotous disease), hyper IgE syndrome (Job Syndrome), HIV/AIDS, especially MRSA syndrome

Pathogenesis of erythema nodosum:

often occurs in association with another condition such as an infection, autoimmune disorder, drugs, certain malignant neoplasms or idiopathic.

Acne

open or closed comedo, pustule, inflamed papule, scarring

Psoriasis

overgrowth of epidermis, presentation (erythematous papules and plaques, silver scale). Nail change (pitting, onycholysis (painless separation of nail from nail bed), discoloration, thickening), peaks in 20s and 50s, triggers (infections, medication, emotional stress, injury), treatment (topical- tar, salicic acid, coritcosteroids, antifungals, emollients)

Eczemas

papulovesicular rash that is pruritic (itchy)

Clinical Features of erythema nodosum:

poorly defined (because deep down), very tender, erythematous plaques and nodules on anterior shins. Fever and malaise. After a few weeks, lesions flatten and appear more like bruises.

Neuropathic Itch

postherpetic neuralgia is one of the most common causes of neuropathic itch. Can occur simultaneously with pain. Often sign of MS. Most distinctive features are a paroxysmal (sudden attack) abrupt onset of itch and duration from seconds to minutes. Often awaken patient from sleep. Similar to Lhermittes's sign (electric sensation that runs down the back and into the limbs ofen elicited by bending the head forward). Impaired synaptic conductivity rather than demyelination might be responsible for these symptoms.

Actinic Keratosis

premalignant lesions, causes (UV light, ionizing radiation, infrared, arsenic, papillomavirus, and scarring, presentation (flat scaly, thicker hypertrophic rough papules with ill-defined borders)

Mycosis Fungoides Clinical Features:

presents in skin first then spreads to lymph nodes and solid organs. Usually remains localized to the skin for many years (indolent behavior). Lesions usually involve truncal areas and buttocks and show a progression from patches to plaques to nodules.

Spreading

progression of skin changes

Describe cutaneous manifestations that may result as a feature of systemic infections S. aureus

pustules, subcutaneous abscesses, purulent purpura, Janeway lesions (endocarditis)

Pemphigus:

rare group of blistering disorders Caused by IgG autoantibodies against desmosome proteins

Squamous Cell Carcinoma

risk (light complexion, fair skin, light hair, blue-eyes) often from conversion of AK, Metastasis is low (2-6%) likelihood of recurrence, diameter, depth, differentiation, growth rate, immunosuppressed patients also have higher risk of metastasis

Describe cutaneous manifestations that may result as a feature of systemic infections Salmonella typhi

rose spots that appear 7-10 days into the febrile course of untreated typhoid fever. Slightly raised, small pink papules in crops of 10-20.

Nikolsky Sign

rubbing or scratching adjacent area causes blister to form within minutes

Papulosquamous

scaly papules and plaques

Lifestyle Changes

sexual risk factors, social habits, dietary changes

Three portals of entry of Anthrax:

skin, inhalation, ingestion.

Plaque

solid, palpable lesion greater than 0.5 cm (may be coalescing lesion of papules)

Pathogenesis erythema induratum:

some sort of vasculitis maybe. Usually no associated underlying disorder

Thick Skin (back, palms, soles of feet)

thick epidermis, interface between dermis and epidermis convoluted, lack of hair, sweat glands deep in dermis

Pathogenesis pityriasis rosea :

think it is a viral etiology but don't know.

Thin Skin

thinner epidermis, dermis contains dense connective tissue, epidermal ridges relatively shallow, keratin layer thin, presence of hair follicles, sebaceous and sweat glands present

Clinical Presentation erythema induratum:

uncommon, adolescents and menopausal women. Erythematous and tender nodulee that will generally eventually ulcerate. USUALLY CALVES NOT SHINS

Pathogenesis of lichen planus:

unknown

Diascopy

using a glass or plastic plate to press against a skin lesion (compresses dermal vessels so blood within vessels flow away from area, blood in dermis or clotted in vessels can't move, indicating hemorrhage in area)

Sturge Weber Syndrome

vascular malfomation that also infolves brain abnormalities (associated co-morbidities may be epilepsy, mental retardation, amongst other issues)

Clinical Features pityriasis rosea:

very common in general population, typically presents in spring or fall. Most common 10-35 yrs of age, increased incidence with close physical contact. NEED TO BE ABLE TO RECOGNIZE IT. HERALD PATCH: SINGLE OVAL SALMON COVERED PATCH, raised border, lighter center, usually on the trunk, then spreads days or weeks later, they itch, christmas treee distribution (trunk along cleavage lines) Looks like ring worm.

Central Tolerance

· Apoptosis of autoreactive cells: Negative Selection · BCR light chain editing · Development of Tregs

Mechanism 1

· Mitochondrial proteins activate Caspase-9 à Apoptosis

Mechanism 2

· Normally, Tcells express Fas · If inadequate costim. then repeated MHC:TCR intrxn causes them to express FasL · FasLà activates caspase-8 à apoptosis

Peripheral Tolerance

· Suppression by Tregs · Anergy · Activation Induced Cell Death (AICD) à deletion by apoptosis

5 Cytolytic

α,β,δ,γ, P-V leukocidin