Tuesday, September 19 (ellen)

Dermatological Pathologies Continued – Tuesday, September 19, 2006 Psoriasis Multifactorial diseases – extrinsic (environment) and intrinsic (genetic) reasons Usually damage to stratum corneum, thereby exposing antigens to body T-cell infiltrate into epidermis T-cells secrete cytokines and growth factors which can lead to: 1) increased keratinocyte replication  acanthosis and extensive hyperkeratosis (silver scales (plaques of dead skin cells) and thicker scales) 2) thinned stratum granulosum – causing more dermis exposure  “Auspitz sign” (pinpoint bleeding) So not quite like squamous cell carcinoma (which shows signs of dysplasia and anaplasia) Lesions are well bordered and pink, with silvery plaques What stimulates the T-cells? Autoimmune associations with gut conditions and Crohne’s disease ND perspective – check gut function (check gluten sensitivity) Imbalance between cAMP (responsible for: increase in maturation and decrease replication) and cGMP (responsible for: increase cell proliferation) ~ so there is increase in cGMP b/c of signal that T-cells send to cytokines ~ you want to downregulate cGMP ~ There are toxins that can increase cGMP (happens when protein is broken by bad bacteria in gut – the broken down protein is the toxin) Tend to be deficient in vitamin D, may benefit from UV therapy Inflammatory Reactions Drug eruptions – common adverse reactions to drugs is inflammation (so make sure you check patient’s medical, diet, and supplement history) Erythema mulitforme – hypersensitivity reaction, can be b/c of infectious agent or drugs ~ multiforme because there are many different forms (macular, papular, pustular, bullous, etc) ~ extensive epidermal degeneration and necrosis ~ due to CD8 T cells that are targeting antigens near the basal cell layer ~ lesions are macules, papules, vesicles, bullae and target lesion (necrotic centre with halo around it) ~ risk of septic shock with the infection b/c it can be quite wide spread Erythema nodosum – a type of panniculitis (inflammation of subcutaneous fat) ~ acute onset and may be idiopathic or with interaction of drugs, infections, inflammatory bowel disease, or visceral malignancy ~ ill-defined, very tender erythematous nodules, may be with fever and malaise ~ old lesions will flatten and bruise (ecchymotic) without scarring ~ there is lymphocyte infiltration Pigmentary Conditions Melanocytes produce melanin (pigment)

Conditions can be b/c of increase or decrease melanocytes or the actual production of melanin ~ ex: mole – increase melanocyte vs. freckle – increase in melanin Vitiligo – loss of melanocytes in epidermis ~ Autoimmune itself and associated with other autoimmune conditions as well ~ Can develop at site of trauma ~ Patchy (local areas of loss of melanocytes), irregular, well-demarcated macules without pigmentation ~ often involved in wrists, axillae, perioral, periorbital, and anogenital regions Side note: Albinism – decrease in melanin, not melanocytes (they lack one enzyme that is involved in melanin production) Lentigo – hyperplasia of melanocytes ~ unique b/c the hyperplasia does not clump like moles, it tends to be in one long flat line just above basement membrane ~ forms darker coloured macule (freckle – more melanin in keratinocytes, not more melanocytes; whereas lentigo is more melanocytes – that’s why develop macule, not papule) ~ “Solar lentigo” in older patients Melasma – increased melanin deposition (especially in basal layers – epidermal type) ~ masklike facial hyperpigmentation ~ usually seen when px is high in estrogen, such as pregnancy (but does not disappear after partum) ~ blotchy, irregular, ill-defined macules ~ worse with sunlight ~ enhanced melanin transfer from melanocytes to other cell types and then subsequent accumulation ~ can also have dermal type: melanin in dermis is phagocytosed by macrophage and released from epidermis into dermis Benign and Premalignant Lesions Seborrheic Keratosis Keratoacanthoma – rapidly developing neoplasm that looks much like squamous cell carcinoma ~ but it heals spontaneously without treatment ~ flesh-coloured, dome-shaped nodules with a central, keratin-filled plug ~ central keratin-filled crater surrounded by proliferating epithelial cells Verrucae – caused by HPV, generally self-limited ~ each type of wart caused by different type of HPV ~ benign, rough surface Melanocytic Nevi Actinic Keratosis Seborrheic Keratosis

Exophytic neoplasm – grows outward and extend far from body Proliferation of basal cell layer Get hyperkeratosis of basal cell layer  and they continue to produce keratinocytes  get keratin-filled cysts (deposit into center of growth) Appear as round, flat, coinlike plaques that vary in diameter, uniformly tan to dark brown As keratin is formed and fills up the lesion, it can form invagination into dermis Look for neoplasma in other sites on body Middle-age to older patients Melanocytic Nevi Benign melanocytic neoplasm A.k.a. “mole” Aggravation of melanocytes at dermis and epidermis junction Eventually grow into dermis = maturation Can elevate above epidermis Can lead to malignant melanoma (See dysplasia, anaplasia, not-defined border, uncontrolled growth) Sporadic Nevi – “here and there” Familial Nevi – all over body, genetic ~ more prone to move into malignant and more dysplasia Tendency to be more sensitive to UV rays Actinic Keratosis Premalignant dysplasia Start with excessive sun exporsure then: ~ 1) basal cell hyperplasia  atypia and dyskeratosis ~ 2) fibroblast damage  abnormal fiber synthesis ~ 3) parakeratosis  thickened stratum corneum (keratin layer of skin) See build up of excess keratin Lesions are tan-brown, red, or skin coloured and have sandpaper-like consistency Find more in ppl with lighter skin or exposure to sun Nuclei are retained in keratinocytes in corneum (usually other pathologies lose nuclei and have only the keratin filled cell)  characteristic feature Malignant Lesion Skin most common site for cancer, not necessarily most deadly type of cancer Squamous cell carcinoma Basal cell carcinoma Malignant melanoma Kaposi’s sarcoma – caused by herpes virus infection ~ malignant cells form solid lesion in connective tissues ~ see nodules that are red, purple, brown, or black ~ usually painless, but can be painful and swollen ~ usually on skin or mucous membrane Squamous Cell Carcinoma

Remember in cancer cells: Dysplasia or anaplasia, unregulated cell replication, lack of differentiation of cells, metastasis, more rapid rate of cell replication, asymmetrical growth Generally small and removable Low invasive potential More superficial layer of skin Sun exposure, industrial chemicals, old scars and trauma, in mouth (people who bite cheeks), viral (especially HPV and bactera, tobacco) Considered carcinoma in situ = carcinoma is contained in the place that it started, no real metastatic properties, no invasion into dermal layer May have invasion through basement membrane (usually removed before it progresses to this stage) Basal Cell Carcinoma Slow growing tumour that rarely metastasize Occur more often at sites that have high sun exposure and lightly pigmented people Pearl coloured papules, often with telangiectasia Some tumors have melanin pigment and therefore can look like nevi or melanoma Two types of growth: 1) Multifocal growths – from epidermis and extends over skin surface; superficial 2) Nodular lesions – grow downward into dermis Malignant Melanoma Big reason – SUN! Predisposing factor – anything that irritates skin Increased incidence Radial growth (epidermis, horizontal growth)  vertical growth (replication INTO the different layers)  metastasis ~ at radial growth stage, usually not malignant, no angiogenesis ~ here, no maturation of cells vertically (in nevi, there IS maturation of cells) ~ lesions are greater then nevi and irregular in contour and pigmentation ~ melanoma cells have larger nuclei Increased mitosis Most important clinical sign of disease is change in colour or size of pigmented lesion Vasculitis Hemangioma Spiderangioma Telangiectasis Cherry angioma ~ these will be covered later, but it is listed here because it appears on skin ~ will see soon in DDx Infectious Conditions Viruses: herpes zoster, human papillomae (verruae), pox (more systemic) ~ needs host machinery

~ incorporates its own DNA into the host’s DNA ~ can have malignant potential in host cell (induce unregulated cell growth because virus wants to grow) Bacteria: Impetigo, folliculitis, boils, cellulites Fungi: ringworm, candidiasis, tinea versicolour ~ ringworm (tinea) – dermatophytes – names based on location they are found ~ Inoculation of keratinocytes by fungi, usually not inflammatory ~ but get secondary bacterial infection and the inflammation is due to this ~ candida (candidiasis) – ubiquitus yeast, opportunistic pathogen, ~ usually involves mucous membranes ~ diaper rash ~ tinea versicolour - caused by the yeast Malassezia furfur or Pityrosporum orbiculare ~ oval or irregularly-shaped spots ~ Occasional fine scalingPale, dark tan, or pink in color, with a reddish undertone ~ Sharp border ~ itching Herpes Simplex Lots of us carry it around, some people manifest it Viral infection of epithelium Becomes inflammatory reaction which creates vesicles (influx of fluid to epidermis and forcing cells apart) Erythematous base (blood flow, hyperemia) under vesicles = hallmark sign of herpes infection Dormancy in a nerve ganglion associated with area with infection, can be re-activated Aggravating factors: STRESS, sunlight, temperature changes, acidic foods, immune function, sleep Lysine controls infection, arginine increase infection 30-100% carrier rate, 20-40% recurrence rate  depends on individual susceptibility Impetigo Superficial bacterial infection in skin Pustular, bullous or non bullous, followed by crusting (often honey coloured) Usually caused by Staphylococcus or Streptococcus HPV Causes warts Epidermal hyperplasia Virus infects cells in epidermis and get lots of growth Rough wart, irregular HPV 16 and 18 are more commonly associated with cervical dysplasia ~ should be included in pap screening