Basic Morphology
Macule - Flat, non-palpable lesions; indicates a lesion w/ color without elevation above skin surface
- Usually < 1 cm (and a “patch” is sometimes used to indicate a flat, non-palpable lesion > 1 cm)
Papule Superficial, circumscribed, palpable lesion elevated above skin surface; diam < 1 cm
Plaque Palpable lesion elevated above skin surface; diam > 1 cm
Nodule Firm (indurated) lesion that is thicker or deeper than average papule or plaque (usually ~ 1cm)
Dermal component that isn‟t palpable (e.g., cyst)
Vesicle Elevated lesion that contains clear fluid; small blister < 1 cm diam
Bulla Elevated lesion that contains clear fluid; large blister > 1 cm diam
(Bullae is plural)
Pustule Superficial elevated lesion that contains yellow fluid (pus) w/in or beneath epidermis, generally protein-rich and
containing neutrophils
Arrangement Can be annular, linear, dermatomal, herpetiform, grouped
Purpura - Extravasated blood that does NOT blanch upon diascopy (pushing a glass slide against the skin)
- If blood in contained w/in vascular system, then it would blanch w/ diascopy
- Note: if palpable purpura, then it is vasculitis until proven otherwise
Erosion Partial loss of epidermis
Ulcer Focal loss of epidermis
Acantholysis Loss of attachment b/t epithelial cells resulting in separation & rounded appearance of these cells (from recoil)
Seen in Pemphis Vulgaris
Acanthosis thickness of spinous layer of epidermis, as result of in # or size (or both!) of epidermal cells (epidermal
hyperplasia)
Seen in Psoriasis
Ballooning Marked swelling of spinous cells d/t intracellular edema
degeneration Seen in Herpes
Granuloma Collection of histiocytes – with or without epithelioid cells & multinucleated giant cells
Tuberculoid granulomas = granulomas surrounded by lymphocytes
Sarcoidal, “naked” granulomas = granulomas without dense inflammatory lymphocytes surrounding them
Hypergranulosis thickness of granular cell layer, as result of # of keratinocytes containing keratohyaline granules
Hyperkeratosis thickeness of horny cell layer – w/ or w/o thickness in granular cell layer
3 types basket-weave, laminated, and compact
Leukocytoclasis Fragmentation of leukocytes, resulting in nuclear “dust”
Seen in LCV (Leukocytoclastic vasculitis)
Lichenification Accentuation of skin markings (clinical term) – may be a response to scratching
Parakeratosis Retention of nuclei in horny layer, assoc/ with or absence of granular cell layer
Seen in Psoriasis
Psoriasiform Epidermral hyperplasia resembling Psoriasis, characterized by regular elongation of rete ridges to about equal
hyperplasia lengths and elongation of dermal papillae
Scale crust Collections of inflamm cells, serum, and/or fibrin and keratotic material, usually covering erosion or ulcer
Seen in Acute Spongiotic Dermatitis
Spongiosis Intercellular edema b/t squamousa cells of epidermis & adnexal epithelium, resulting in widened intercellular
spaces. Marked spongiosis may lead to vesicle formation
Seen in Acute Spongiotic Dermatitis
5 inflammatory reactions
Contact Dermatitis 1. Papulosquamous: conditions that are red and scaly
has 2 types True (20%) and Irritant (80%) 2. Eczematous: 3 stages acute, subacute, chronic
3. Vascular: diffuse red eruptions like hives & drug-induced skin reactions
Allergic Contact Dermatitis 4. Dermal: conditions w/ deep component in skin, little or no epidermal
- Is “true” dermatitis 5. Vesicobulbous: associated w/ blisters
- Common causes nickel and poison ivy (hapten1 of poison ivy is Urushiol)
- Pathophysiology
o Specialized form of delayed, Type IV hypersensitivity contrast w/ Atopic Dermatitis
- Histology
o Acute: spongiosis, vesiculation, eosinophils
o Chornic: psoriasiform epidermal hyperplasia
- Gross Appearance often linear or geometric, and well-demarcated
o Usually localized to site of contact (helpful for hx)
- Course of Disease/ Clinical stages
o Acute: inflammatory mediators cause spongiosis (histological) vesicles & blisters (clinical manifest)
o Subacute: vesicles rupture erosions, scales (dried blister roof), and crust (dried serum/ blood)
o Chronic: scratching & rubbing result in epidermal hyperplasia (histologically) thickening and lichenification (clinical manifest),
become psoriatic
- Gold standard for Dx patch testing (using a standard panel of 24 things; evaluation @ 48, 72 hours to see if it‟s delayed-type hypersensitivity)
- Differential Dx “itch-scratch,” irritant contact, atopic dermatitis, stasis dermatitis, seborrheic dermatitis, erythematous form of acne rosacea
Atopic Dermatitis
- Pathophysiology Allergic Dermatitis is Type IV hypersens
- Clinical Stages
o Acute Type I hypersensitivity
o Subacute
o Chronic Type IV hypersensitivity
- Eval of PT hx & PE usually sufficient, but also… biopsy to confirm dermatitis; also can do patch test
- Treatment remove causative agent (#1), topical steroids (if severe), anti-histamines (that H1 receptors)
LCV (Leukocytoclastic Cutaneous Vasculitis), a small vessel vasculitis… i.e., Hypersensitivity Vasculitis
- DEF: Diverse group of disorders: segmental inflammation + necrosis of blood vessels
- Etiology may be 1, d/t a systemic disorder, or idiopathic
- Pathophysiology Type III hypersensitivity, with circulating immune complexes depositing in small blood vessels, complement, and attract
neutrophils degranulation of neutrophils and monocytes release of lysosomal enzymes and toxic O2 metabolites tissue damage &
vascular injury
o Involves only small vessels, esp post-capillary venules!
- Appearance
o Palpable pupura ( doesn‟t blanch on diascopy), edematous urticaria-like lesions, hemorrhagic macules or vesicles
o Lesions usually occur @ lower extremities, dependent areas, or pressure points
o Extra-cutaneous involvement occurs but is uncommon… GI, genitor-urinary, or neurological sx should raise suspicion about systemic
vasculitis being the Dx
o Typically presents 7-10 days after exposure to inciting agent
- Biopsy would should lymphocytic infiltrate of blood vessels
- Treatment
o Treat underlying cause (esp if d/t meds, infections)
o H1 blockers (antihistamines) to alleviate sx of palpable purpura
o H1 blockers + NSAIDs
o Colchinine can be added or substituted for above agents; if not effective, then trx with Dapsone
o IFN clears lesions in Hep C
o Steroids: rarely indicated!
1
Hapten = small molecule that can elicit an immune response only when attached to a large carrier (e.g., a protein)
Urticaria
- Epidemiology
o Lifetime occurrence: 1-5%
o Women > men, except in delayed-pressure urticaria
- Subtypes
o Acute (if < 6 weeks): idiopathic (50%), URTI (40%), drugs (9%), food (1%)
o Chronic (if > 6 weeks): 50% free in 1 year; 65% free in 3 yrs; 85% free in 5 yrs
- Pathophysiology
o Type I hypersensitivity Ag induces cross-linked of IgE bound to mast cells, with release of vasoactive mediatory (pre-formed)
Note that some ppl can have autoimmune urticaria (anti-FcR, anti-IgE antibodies)
o Secretory granule preformed mediators histamine, proteoglycans, tryptase & chymas, carboxypeptidase A
- Histology
o Sparse superficial peri-vascular & interstitial inflammatory infiltrate
o Mixed-cell infiltrate including activated T-cells, monocytes, eosinophils, & mast cells
- Clinical Features
o History of allergy
o Wheal: white or red evanescent plaques, d/t local edema… usually lasts 12-24 hrs
o Flare: a “red halo” that surrounds the wheal
o Pruritic or stinging
- Systemic associations, which may indicate anaphylaxis palpitations, nausea, malaise, dizziness, syncope, wheezing, vomiting, diarrhea, fever,
chills, abdominal pain, arthralgia, myalgia, headache
- Diagnosis skin biopsy is not routine and is only indicated if lesions last > 24 hrs
- Treatment
o Cromoglycate (mast cell stabilization), Cromolyn sodium
o Anti-histaminergics (mainstay) + LK antagonists (Monteleukast)
They work synergistically
o Doxepin (a TCA with anti-H1 receptor properties and activity against PAF)
o Corticosteroids AA pathway mediators & cytokines, but have NO effect on histamine
o Immunosuppressants (e.g., Cyclosporine and FK506) cytokine production
o Avoid mast-cell degranulating agents e.g., EtOH, anti-cholinergic preparations, ASA, NSAIDs, narcotics, Polymxyin B
Erythema Multiforme
- Acute, self-limited skin disease
- Pathophysiology
o Skin-directed immune reaction in predisposed individual in the setting of an infection or less commonly, other insult HSV is most
commonly associated infection (HSV-1 and HSV-2)
Also: bacterial infection by Mycoplasma pneumonia
Fungal infections
Drugs < 10%
Exposures (e.g., poison ivy)
Systemic disease (rare) inflamm bowel disease, SLE, Behcet‟s Disease
o Evidence for replicating HSV in lesions
HSV proteins found in affected epidermis
HSV DNA in early red papules or outer zone of target lesions in 80% of PTs
Virally-encoded antigens on keratinocytes
o EM lesion thru part of HSV-response
HSV DNA recruits IFN-producing Th1 cells
Immune response to auto-antigens released by lysed/ apoptotic viral antigen-containing cells
- Findings
o Keratinocyte necrosis; spongiosis; superficial dermal edema
o Small vessel vasculitis: extravasated RBCs, perivascular inflammation
- Clinical Presentation
o “Target” or “iris” lesion (fairly distinctive usually a clinical dx)
Present within 24 hrs
Pruritus or burning may accompany the lesions (“skin pain” might be CC of PT)
o Mild cases: EM minor (involving skin + 1 mucosal surface (e.g., vaginal mucosa))
Lesions are non-blanching
o More severe cases: EM major or Stevens-Johnson Syndrome (skin + more than 1 mucosal surface)
Most extensive & aggressive form of SJS: Toxic Epidermal Necrolysis (TEN)
TEN is 1 in a million of the normal pop, but 1 in 1000 in those w/ HIV
o No sequelae, except ocular sequelae in EM major without adequate eye care
o Recurrent is common in HSV-related EM
- Course of Disease
o Of those w/ SJS & TEN: 20-30% mortality
- Treatment
o Topicals
Antiseptics for eroded skin
Antiseptics/antihistamine/local anesthetics for mucosal lesions
Ophthalmic preparations for eye care (consult ophthalmology)
o Systemic
Treat identifiable precipitators when possible though often only symptomatic treatment needed
Oral antihistamines may reduce stinging and burning
In severe EM, early oral corticosteroids considered
o Prophylaxis
Acyclovir shown effective in double-blind, placebo controlled study, though valacyclovir and famcyclovir also employed
Occasionally benefit extends even after discontinuation of antiviral
Pemphigus Pemphigus
Foliaceus Vulgaris
Antigen Dsg-1 Dsg-3
- Treatment (depends on severity and progression) & Prognosis goal is to interrupt antigen processing, cytokines (like TNF, IL-1, IFN),
chemotaxis
o Corticosteroids are mainstay (topical, intralesional, or systemic)
o Hydroxychloroquine and Chloroquine (antimalarials) are used to control skin manifestations
o Other Trx immunosuppressant drugs like Tacrolimus, TNF inhibitors (Infliximab), surgical excision
o About 60% spontaneously resolve and 10-20% spontaneously resolve w/ steroid use
o > 80% with EN and acute Sarcoid have spontaneous resolution
Acute, transient Sarcoidosis is a good prognostic factor
o Chronic & progressive in 10-20%; fatal in 1-5%
Dermatophyte Infection
- Most common players Tinea rubrum (skin & nails); T mentagrophytes, E. floccosum (causes tinea pedis)
- Pathology
o Hyphae in Stratum Corneum
Spongiosis, papillary dermal edema (2 to inflamm rxn to fungi in Stratum Corneum)
- Presentation
o Scaly erythematous plaques, annular shape
o Factors that indicate Dermatophyte infection
Inoculum size
Suitable environment (like hydration, friction, laceration, heat, darkness, occlusion)
Growth rate of fungus has be to faster than your skin turns over
o Tinea cruris (“Jock Itch”) – diaper rash, could occur in elderly
o Majocchi’s Granuloma: granulomatous lesion of hair follicle, generally associated with T. rubrum (and requires biopsy for dx and
oral anti-fungal for treatment)
o Kerion: boggy, oozing inflamm reaction of the head in response to fungus (tinea capitis)
Trx with Prednisone to inflammation
o Tinea Unguium (Onychomycosis, i.e., dermatophyte infection of the nails): fungus of the nail. Nail thickens, becomes more
brittle; fungus lefts plate and creates a potential space there… keratinization develops. This is located distally
Contrast with nail changes in AIDS, where you have proximal white subungual onychomycosis. Caused by Tinea rubrum,
which is really only seen in the HIV population
o Tinea versicolor: “spaghetti and meatballs” appearance on KOH prep; Malassezia furfur is the organism that causes this skin
hypopigmentation
- Investigations KOH prep
Chromoblastomycosis (Subcutaneous Mycoses)
- Caused by dematiaceous – a cluster of pigmented fungi. These fungi are isolated from wood, plant debris, or soil
o Distribution of these fungi mainly Central America, South America, Africa, & Caribbean islands
- Histopathology
o Granulomatous rxn with giant cells
o Fungus appears as brown, spherical cells w/ thick, dark cell walls and coarsely granular & pigmented
o Spores will be found inside the giant cells and are pathognomonic w/ Chromoblastomycosis called “Copper Pennies” or “Medlar
Bodies”
o Mixed dermal infiltrate, consisting of neutrophils, histiocytes, epithelioid cells, giant cells, lymphocytes, eosinophils, and plasma cells
- Clinical Presentation
o Begins as small, pink, scaly papule or warty growth, and spreads slowly
o Warty papule expands to become nodular, timorous or verrucous like a cauliflower
o Extremities usually become swollen
o Usually affects one leg or foot, but can also affect hand or upper trunk
- Complications if spreads to lymphatics, then lymphedema (leading toelephantiasis), and rarely, Squamous cell carcinomas in some chronic
lesions
- Diagnosis
o KOH (may show pigmented hyphae)
o Fungal culture
- Treatment
o For superficial infections, trx with topical azole cream
o For tinea capitis and Majocchi‟s granuloma, systemic therapy like Griseofluvin and Itraconazole po steroids for PTs with Kerion
formation
o For deep fungal infections, surgical excision („debulking‟), Itraconazole, Terbinafine
Human Papillomavirus
- Virus info family of non-enveloped dsDNA viruses that are resistant to heat & dessication
- Epidemiology
o Cutaneous warts v. common in children 3-12 yo… up to 10% of pop is affect
o Lower genital tract HPV common among adolescents & adults … affects 20 million in US
o Anogenital warts uncommon in pre-pubertal children
Should consider sexual abuse, esp if child is > 3 yo, perianal and perivulvar location, the mother has no hx of condylomas
Inoculation at birth
- Commonly induce papilloma (i.e., warts, verrucae) – which are benign proliferations of skin & mucosa
- Many subtypes of HPV with oncogenic potential (to cause cervical CA and penile squamous cell CA)
o HPV 16, 18, 33, 45 are implicated in 80% of worldwide cervical cancers
o Viral proteins E6 and E7 are important in the induction of cervical CA by HPV types 16 & 18 (p53 and Rb gene inhibition)
o Genomic instability and thus, oncogenicity, is promoted by
Viral pathogenic factors (like integration of HPV DNA)
Non-viral factors (e.g., smoking, cervical inflamm, parity, long-term OC use, immune suppression)
- Histopathology
o Koilocytes, which are a type of dysplastic squamous cell that are large, pale-staining keratinocytes w/ eccentric nuclei surrounded by
perinuclear halo
o Acnthotic epidermis with “church spire” papillomatosis, hyperkeratosis, and vertical tiers of parakeratosis
o Elongated rete ridges that point radially towards center from periphery (contrast with psoriasis and long-wise hyperplasia of rete
ridges)
o Dermal capillary vessels are prominent, occasionally thrombosed
- HPV Diagnosis PE, histopath, PCR, and immunohistochemical detection of HPV structural proteins
- HPV Treatment will always involve destructive trx since warts are difficult to remove
o Destructive or Ablative therapy (cyrotherapy, curettage or surgical excision, TCA, electrodessication w/ local anesthesia, laser trx)
o Immunotherapy e.g., Imiquimod (Aldara®)
Arthropod Bites
- Arthropods includes insect (6 legs) and arachnids (8 legs)
- Pathogenesis Note that arthropods can also serve as vectors to inoculate infectious agents (e.g., B. borgdoferi)
o Many rxns are mediated Type I (immediate) or Type IV (delayed) hypersensitivity rxns
o Inflamm can result from either
Toxic (e.g., venom)
Allergic mechanism (immunologic rxn elicited, involving release of histamine from mast cells)
o Non-immunologic inflammation results from tissue damage or from necrosis (e.g., spider bit by Brown Recluse Spider)
o Human disease is produced by biting or stinging, injecting toxins, burrowing into skin, as vectors for other diseases
o Most bite reactions are d/t host response to antigens present in saliva
- Histopathology
o Spongiosis
o Papillary dermal edema vesiculation
o Eosinophils admixed w/ lymphocytes
- Presentation
o PTs may be present with single or multiple erythematous papules, urticarial lesions, papulovesicles or vesicles
o “Papular urticaria” (papules are edematous) refers to hypersensivity rxn to certain insect bites, particularly mosquitoes, fleas, mites,
and bedbugs
- Labs, Biopsy, Treatment
o Dx is usually clinical
o 1 therapy is to remove offending insect from environment
o Treat pets & home as required
o Trx with topical steroids and antihistamines
o Most insect bites resolves spontaneously and uneventfully
Scabies
- Epidemiology
o Worldwide occurrences
o Spread by close personal contact, sexual or otherwise. Can also be transmitted by fomites (it can survive for 3 days off of human skin)
o Immunocompromised (elderly, HIV+, transplant) and those with sensory functions: Crusted Scabies (Norwegian)
- Pathogenesis
o Entire 30-day life cycle is completed in human epidermis
o Usually < 100 mites on infested host , however there may be millions with crusted scabies
- Presentation
o 2-6 week incubation period before immune system becomes sensitized and sx develop in 1 st-time infestation
o 24-48 hr incubation period in subsequent infestations
o Intense Pruritus
o Erythematous papules burrows w/ commonly associated excoriations, vesicles, eczematous dermatitis and 2 bacterial infection
o Cutaneous lesions are symmetrical, typically involving interdigital webs, wrists, axillae, genitals, and areolae
- Investigations
o Scabies prep scalpel or curette w/ mineral oil to scrap skin and inspect those scrapings for mites, eggs, or fecal pellets using light
microscopy
o
- Treatment
o Systemic trx needed for those who are Immunocompromised, sensory function, or dementia (those who cant‟ register that they feel
itchy)
o Permethrin cream (5%)
o Ivermectin (po), which is avoided in pregnancy and kids
o Wash bedding, clothing and towels with hot water & dry on high heat to potential fomite transmission
o Treat family members as may be asymptomatic carriers
o “Post-scabetic pruritus” can persist for 2-4 wks post tx
Lice
- Pediculus capitis (head lice)
- Lice are obligate human parasites that feed exclusively on host blood every 4-6 hrs
- Female louse lays eggs close to scalp for warmth
- Transmission: head-to-head contact as well as fomites (but rarely survive if > 24 hrs away from host)
- Primary vectors of disease
o Epidemic typhus (Rickettsia prowazekii)
o Relapsing fever (Borrelia recurrentis)
o Trench fever (Bartonella quintana)
- Treatment
o Permethrin (synthetic pyrethroid) cream – must treat ALL hairy area, shaving is effective; must also treat sexual partners of affect
person
o Malathion (cholinesterase inhibitor)
o Invermectin (oral or topical) – avoid in pregnancy and toddlers
o Treat clothing, bathe the PT, clothing can be fumigated and washed w/ hot water or discarded
Rubeola (Measles)
- Incidence with vaccination, esp in the US
- Pathogenesis
o Paramyxovirus family, Rubivirus genus – ssRNA
o Highly contagious & is spread via resp droplets
o Humans are natural host and reservoir of infection
o Viral replication in resp tract‟s epithelial cells lymphoid tissue & blood viremia
Can spread to lungs, liver, and GIT
- Histopathology superficial perivascular infiltrate w/ mild spongiosis but this is NON-specific (in Rubella too)
- Presentation
o Incubation period: 10-14 days
o 3 Cs of the prodrome cough, coryza2, conjunctivitis
o Koplik spots are classic it is controversial whether or not the rash is result of Ag-Ab complex deposition or direct viral invasion of
tissue
Genuine macular + popular rash!
o Cephalo-caudal spread without fading
- Complications
o Otitis, pneumonia, encephalitis, myocarditis, and (rare) subacute sclerosing panencephalitis
- Investigations
o Lab dx not necessary
o Can confirm w/ isolating the virus from nasopharyngeal sections, immunofluorescence, or serologic assay
- Treatment
o No specific anti-viral therapy
o Supportive
o Prevention is key (with MMR vaccine)
2
Coryza is inflammation of mucous membranes within nasal cavity; resembles head cold
HIV, AIDS
- Almost all HIV+ pts will develop some disorder during the course of their disease; that‟s why it‟s important to recognized the diff typical and
atypical cutaneous manifestions of the skin diseases that affect this population
- Acute Retroviral Syndrome: seen in 50-90% PTs and about 50-75% will develop a rash
o Earliest cutaneous manifestation in seen during this time
o Characterized by mononucleosis-like syndrome w/ fever, malaise, myalgias, lymphadenopathy
o Most common rash is “morbiliform”
- Severity & extent of HIV-related skin diseases correlates w/ in CD4 counts… early on, they present quite typically but as CD4 # , then the
conditions become more chronic, severe, and resistant to usual therapies
o With CD4 even more, then the skin manifestations are even more unusual cutaneous Cryptococcus, Kaposi‟s Sarcoma, Bacillary
Angiomatosis
- Infections: generally present when CD4 < 300/mm3
- Most common are muco-cutaneous candidiasis & herpes zoster
- Opportunistic infections begin to develop when CD4 count approaches 200/mm3
o Fungal infections
Candidiasis 90% of PTs develop thrush
Intertriginous candidiasis, chronic paronychia3, onychodystrophy, refractory vaginal candidiasis
Dermatophytes cutaneous involvement can be atypical, proximal white onychomycosis
o Disseminated fungal infections Cryptococcus, histoplasmosis, coccidiomycosis, blastomycosis, etc.
Variable morphology: pustules, papulonodules, patches, plaques, ulcerations… should do Bx or culture
o Bacterial infections TB, NMTB (atypical TB), Staph, Strep, Bartonella
Bacillary Angiomatosis red-to-purple, violaceous vascular-appearing papules or nodules ulcers
Caused by Bartonella henselae (cat scratches, bites) or Bartonella Quintana (assoc w/ poverty & poor hygiene)
( DDX: Kaposi‟s Sarcoma )
o Viral infections
Chronic HSV persistent erosions & ulcerations; consider testing for Acyclovir resistance
Warts
Molluscum Contagiosum favors neck, intertriginous areas; may spontaneously regress when PT is in anti-retroviral
therapy like HAART
HHV-4 Oral Hairy Leukoplakia in ¼, and this is a predictor of progression to AIDS. The lesions themselves have no
malignant potential
VZV HIV+ pts have 7-15x greater relative risk of developing Herpes Zoster; can be multi-dermatomal, ulcerative,
chornic, verrucous widely disseminated
May occur as part of IRIS (immune recovery syndrome). (If the person is put on HAART, may have exuberant
response to infection)
HPV higher risk of developing CIN & AIN
More rapid progression from low-grade to high-grade pre-malignant lesions
Recurrent rates of cervical cancer after standard trx are also higher in those who are HIV+ (compared to those who
are HIV)
o Parasitic infections scabies, demodex
Scabies Crusted (Norwegian): keratotic plaques that may not be pruritic and burrows might not be apparent; can scrape
hyponychium
Demodicosis mite that invades follicles on the face, rosacea-like presentation
- Non-infectious cutaneous disorders
o Seborrheic dermatitis a greasy dermatitis especially affecting the chest & upper back, b/c of the # sebaceous glands there
o Psoriasis
o Eosinophilic folliculitis recurrent crops of sterile pustules and papules; pruritus in ½ the PTs
o HIV-associated lipodystrophy
Not the same as AIDS wasting
Cushingoid appearance, loss of peripheral fat buffalo hump
Visceral fat accumulation
Hypertriglyceridemia and insulin resistance
Trx with autologous fat (excise the excess fat and inject it into the sunken cheeks of the AIDS patients), poly-L-lactic acid,
and silicone
o Generalized pruritus
Switch hypothesis where Th1 cells switch to Th2 cells Atopic dermatitis, Papular pruritic disorders (i.e. hypersensitivity),
Papular pruritic eruption of AIDS
- Hair & Nails in HIV
o Alopecia 2 to Tinea Capitis
o Telogen effluvium from serious infections w/ fever
o Straighter, softer, silkier, lusterless or dull hair
o Sudden graying of hair
o Proximal white subungal onychomycosis
o Chronic candidiasis
o Melanonychia from Zidovudine
o Beau’s lines (lines and ridges along the length of the nail), psoriatic nail pitting, onycholysis
o Trichomegaly assoc w/ IFN and Zidovudine: elongation of eyelashes
3
Paronychia: infection where the skin meets the nail
- Neoplastic HIV-related Cutaneous Disorders
o In normal population, BCC > SCC, but in HIV+ patients, SCC > BCC
o Kaposi’s Sarcoma
Seen especially in homosexual men, does NOT correlate w/ amount of immunosuppression
Cases with advent of HAART
Purple papules to plaques with ulcerated nodules
Initially upper body: along skin lines or trauma sites
Face, nose, oral mucosa, GI tract and lymphatics
- Adverse Cutaneous drug Eruptions
o Occur more commonly in HIV+ individuals than general population
o Morbilliform eruptions, urticaria, pruritis, vascultive, erythroderma, photodermatitis, SJS, TEN
Photobiology
- UV radiation can be reflected, transmitted, scattered, or absorbed
- For a photobiologic effect, radiation must be absorbed in the stratum corneum and epidermis by chromophores, with absorption in the UVB
range
UV-A UV-B
- Contributes to tumor promotion - Contributes to tumor initiation
- May accelerate carcinogenesis - Isomerizes to form Vit D3
and can induce matrix - Is the main contributor to erythema
metalloproteinases that tumor - Causes delayed tanning (visible 72 hrs)
aggressiveness - melanocyte # and tyrosinase activity; also, epidermal thickening When UVB is
- Causes more oxidative stress, most absorbed, it induces DNA changes (C-T transition mutations, called “UVB
cytotoxic than UVB signature”… these are seen in p53 mutations)
- Causes immediate pigment - Also induces changes by forming pyrimidine dimers b/t adjacent pyrimidine bases
darkening b/c it photo-oxidizes pre- - UVB absorption also causes trans-urocanic acid to change to cis-urocanic acid
existing melanin - Langerhans cells, suppressor T cells (which induces susceptibility to tumor),
Th1, Th2
- Also: mast cell degranulation upon sun exposure… so, some ppl go out into the sun and
they start to itch
- Induces Neoplasia in mice
- Disruption of Hedgehog-Patched Signaling - Tumor Suppressor P53 mutation occurs often, PTCH genes
Pathway (PTCH genes) - Also: CDKN2A (cyclin-dependent kinase inhibitor 2A) mutation
Pathogenesis
bite of out it
- Pink or pigmented with brown spots
- Surgical excision (5-yr cure rate of ~90%) - Need to biopsy!
- Micrographic surgery (5-yr cure rate of 99%) - Cyrotherapy: 98.8% cure rate
- Cyrosurgery, radiotherapy, Imiqinod - Topical 5-FU
- Imiquinod, chemical peel (removal of epidermis), curettage
Treatment
- Surgical excision
- Radiotherapy
- Imiquinod
Recurrence potential, & can be locally invasive/ - Prognosis of AK is excellent
disfiguring - 10-yr survival for SCC if regional metastasis is 20% and distant
Prognosis/
course of
ursor
Prec
- Genetic markers, UV exposure, pigmentary characteristics, #, dysplastic nevi, personal or family hx, upper socioeconomic
Risk
Fact
ors class, immunosuppression
- > 60% arise de novo, but 1/3 are associated w/ nevus remnant (SEE BELOW)
- CDKN2A (cyclin-dependent kinase inhibitor 2A) mutation on Chr. 9q21 significant
Pathoge
- Superficial spreading: most common type, fair skin; trunk & legs, asymmetric macule; radial growth, seen in repeated
sunburns
- Nodular: grows vertically, 2 nd commonest, 6th decade, M>F, no radial growth; no macular component
- Lentigo maligna: uncommon, 7th decade; face, actinic background and chronic sun exposure; MMIS
- Acral lentiginous: in darker skin types, 7th decade, palms, soles, nail bed.
Clinical Present.
- Variant is Subungual Melanoma: longitudinal pigmentation; Hutchinson‟s sign (pigment in proximal or lateral nail fold)
- Amelanotic Melanoma: no clinically evident pigment; erythematous papule or nodule; diagnostic delay is common
- Ocular Melanoma: rare, can be in conjunctiva or uveal; risk with DN syndrome and melanosis oculi
- Mucosal Melanoma: rare, in oropharnx or nasopharynx; vagina, anus. Present at advanced stage
- Nevoid Melanoma: clinically indistinct features
- Primary prevention avoid exposure to UV light, sunscreen use
- Secondary prevention skin cancer screening, educational campaigns
Trx
- Prognosis depends on tumor thickness, ulceration, age, sex, anatomic size, # of lymph nodes involves, side of distant
metastasis
Common Acquire Nevus
- Benign skin neoplasm
- Etiology not well-understood, but d/t genetic factors (familial clusters) and environmental agents (UV exposure, etc.)
- Pathogenesis
o Melanocytic nevi are thought to originate from melanoblasts, that migrate from neural crest to epidermis
o Nevi are thought to be either hamartomas or benign proliferations w/ some growth advantage over surrounding basilar melanocytes
- Presentation
o May be junctional, intradermal, or compound
o Atypical or “dysplastic” nevi share clinical features of melanoma
o Intradermal nevus: Superficial papillary dermal nests of round pigmented cells & deeper cords of lightly pigmented or nonpigmented
cells
o The person might use SPF, avoid mid-day sun, but has hx of childhood sunburns
- Progression of disease
o Approx 1/3 of melanomas are assoc w/ nevus remnant
- Treatment
o Sun protection, dermascopy, sequential digital imaging
o Remove if the lesion changes, has atypical clinical appearance, cosmetic reasons, and if it causes repeated irritation
Seborrheic Keratosis
- Epi uncommon before age 30, possibly AD inheritance
- Presentation often in sun-exposed area
o Occur on hair-bearing skin
o Face, neck and trunk commonly affected
o Lesions may be yellow, tan, brown
o Keratotic plugging with follicular prominence contributes to stippled texture
o “Sign of Leser-Trélat”
Abrupt appearance or rapid expansion in number and/or size of SK‟s
If with pruritus, may suggest the presence of visceral malignancy
GI adenocarcinoma most common which may have tripe palms and acanthosis nigricans
Possible that growth factors active in malignant tissues stimulate epithelial hyperplasia
Non-cancerous states may also be associated with increase in size and number of SK‟s, including psoriasis and pregnancy