General Dermatology

Dorthe Aslaksen Dermatology Autumn 2019
General dermatology
1) The structure of the skin
Basics
- Weight: 4 kg
- Cover 2 m2
- Barrier: external threats, loss of body constituents (water)
- Three layers
o Epidermis
o Dermis – connective tissue
o Subcutis/hypodermis – fat abundance
Epidermis: varies in thickness. 0,1 mm on eyelids, almost 1 mm on palms and soles. Thickness is kept constant by cell
proliferation in the basal layer.
- Layers of closely packed cells. Most superficial skin cells have no nucleus and an abundancy of keratin →
keratinized stratified squamous epithelium
- Adhere to the dermis at basement membrane. Dermal papillae are projections of dermis into the epidermis.
o Adhesion
o Nutrient supply, since epidermis is avascular
- The journey of one cell from the basal layer to the surface takes 30 days; transit time
- Stratum basale
o Single layer of columnar cells, growth fraction is normally 30%
o Attach to basement membrane via hemidesmosomes
- Stratum spinosum
o Composed of keratinocytes: larger than basal cells, synthesize keratin and produce vitamin D
o Cells firmly adherent to each other by long spinous processes, desmosomes and cadherins
- Stratum granulosum
o Cells contain keratohyalin granules (basophilic on HE)
- Stratum lucidum
o Only in areas with thick skin; palms and soles
o Keratohyalin granules dissolved and the content are dispersed throughout the cytoplasm
o Keratohyalin transformed to translucent substance eleidin
- Stratum corneum
o Piled up layers of dead cells (corneocytes), separated by lipids in the intercellular space → effective
barrier towards water loss, invasion of infectious agents and toxic chemicals
▪ Solvent extraction → impaired barrier function
• Seen in essential FA deficiency
▪ Penetration depends on the concentration difference across the epidermis and the
thickness of the stratum corneum
• Increased temperature aids in penetration
o No nucleus
o Continuous shedding of keratin → removal of harmful exogenous substances, passive barrier to
infective organisms
o Antimicrobial substances; first line immune defence
- Keratins are the main intermediate filaments in the epithelial cells
o Mutations → epidermolysis bullosa, bullous ichtyosiform erythroderma
o One acidic and one basic keratin polypeptide → larger double fibrils. Cross-linked by cysteine.
▪ Epidermal strength, ability to withstand injury
o Different types of keratins found at different layers of the skin
▪ Healthy skin, terminally differentiated cells: keratins 1 and 10
▪ Normal basal cells: keratins 5 and 14
▪ Hyperproliferative states as psoriasis: keratins 6 and 16
- Other cells of epidermis (15%)
o Melanocytes
▪ Origin: neural crest cells
▪ Suprabasal localization
▪ Epidermal melanin unit: melanocyte + multiple keratinocytes
▪ Melanosomes “injected” into keratinocytes to provide pigmentation
o Langerhans cell
▪ Dendritic cell, basal localization
▪ Lack desmosomes and tonofibrils, lobulated nucleus
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▪ 800 Langerhans cells per mm2

▪ UV radiation and topical glucocorticoids reduce density of Langerhans cells
o Merkel cell
▪ Transducers for fine touch
▪ Mostly basal location
Dermo-epidermal junction
- Hemidesmosomes minding to intermediate filament components of keratinocytes
- Lamina densa, lamina lucida
Dermis
- Support of dermis
o Structurally
o Nutrients
- Varying thickness
- Thickness and elasticity decrease with age
- Dermal papillae into epidermis
o Readily seen on fingertips as fingerprints
o Increase contact area between the two layers → facilitate firm adhesion
- Components: cells, fibres, amorphous ground substance
- Cells of the dermis
o Fibroblasts (main): synthesis of collagen, reticulin, elastin, fibronectin, glycosaminoglycans
o Mononuclear phagocytes
o Lymphocytes
o Langerhans and dendritic cells
o Mast cells
o Merkel cells
- Fibres of the dermis
o Collagen packed in bundles (70-80% of dry weight of dermis)
▪ High tensile strength
▪ Triple helix stabilized by covalent cross-links of lysine and hydroxylysine
▪ High proportion of proline and hydroxyproline
▪ Glycine every third amino acid
▪ Defect in enzyme needed for collagen synthesis: Ehlers-Danlos syndrome, osteogenesis
imperfecta
o Elastins intermingled with collagen (2% of dry weight)
▪ Return of skin to unstretched state
o Reticulins
▪ Fine collagen fibres
▪ Neonatal skin, around blood vessels
- Ground substance of dermis
o Hyaluronic acid
o Dermatan sulphate
o Smaller amounts of heparan sulphate and chondroitin sulphate
o Proteoglycans complexed to core protein
o Function: binds water, act as lubricant between collagen and elastic fibres, provides bulk to the
skin
- Muscle
o Smooth: arrector pili, dartos muscle, nipple erection
o Striated: platysma, muscles of facial expression
- Blood vessels → temperature control, under sympathetic control
o Deep and superficial plexus in parallel with each other
o Shunting of blood from deep to superficial plexus
- Lymphatics
o Blind ended capillaries in dermal papilla, pass to superficial lymphatic plexus in papillary dermis
- Nerves
o Most free nerve endings terminate in the dermis
o Nociceptors, mechanoreceptors, autonomic nerves supplying blood vessels, arrector pili muscle
o Stimulation of free nerve endings → itching. High density of such nerve endings are called itch
spots.
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2) Skin appendages
Skin associated structures serving a particular function including sensation, contractility, lubrication and heat loss.
- Types of appendages: hair, glands, nails
Hair
- On entire body except lips, glabrous skin of palms and soles, glans penis and vulvar introitus
- Types
o Lanugo – fine, long fetal hair from 20th week of gestation. Shed around 1 month before birth.
o Vellus – fine, short, unmedullated hairs covering most of the body.
o Terminal – long, coarser, darker medullated. Scalp, eyebrows, eyelashes, pubic and axillar hair.
Influenced by circulating androgens, e.g. during puberty.
- Structure from outside and in (hair follicle = oblique invagination of epidermis containing a hair)
o Connective tissue of dermis
o Hyaline membrane
o Outer root sheath
▪ A thickening, called the hair bulge – insertion of arrector pilli muscle. Area contains
follicular stem cells → regeneration of hair follicle and sebaceous gland.
o Inner root sheath
o Hair
▪ Cuticle
▪ Cortex
▪ Medulla
o Bottom of hair: hair matrix, melanocytes, hair papilla indenting into hair bulb with capillary for
nutrients
- Hair cycle
o Anagen – active phase (85% of follicles on scalp)
o Catagen – mid stage, follicular regression
o Telogen – resting phase, hair is shed. 15% of hair follicles on scalp
Arrector pilli
- Smooth mm contracting with cold, fear and emotion
- Erection of hair, goose bumps
- Attached to hair bulge of outer root sheath
- Sympathetic innervation
- Insulation through air entrapment
Sebaceous glands
- Majority associated with hair follicles in which they empty
- Free sebaceous glands in eyelid (meibomian glands), mucus membranes, nipple, perianal region, genitalia
- Multilobulated
- Secrete sebum through holocrine secretion
o Triglycerides, FFA, wax esters, cholesterol
- Function: lubrication, water isolation, protection from drying, mild bacteriostatic and fungistatic mechanism
- Stimulated by androgens
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Sweat glands, two types: eccrine and apocrine. Up to 10 L/day can be secreted.
- Eccrine sweat glands
o 2-3 million over the body
o Concentrated in axilla, palms, soles
o Tightly coiled gland deep in dermis, duct passing to the surface
o Merocrine secretion
o Sweat composition
▪ Hypotonic
▪ pH 4-6,8
▪ contains Na, K, Cl, lactate, urea, ammonia
o stimulated by thermal stimuli, emotional stimuli and gustatory
o sympathetic cholinergic innervation
- Apocrine gland
o Limited to axillae, nipples, periumbilical area, perineum, genitalia
o Coiled tubular glands, larger than eccrine glands, deep in dermis
o Secrete into hair follicles through apocrine secretion
o Odourless, but bacterial actions responsible for body odour
o Innervated by adrenergic sympathetic fibres
Nails
- Densely packed keratin
- Protection of fingertip
- Facilitate gripping and tactile sensitivity
- Derived from nail matrix
- Cells in proximal nail bed which proliferate and keratinize
- Nail bed can also produce small amounts of keratin contributing to nail plate
- Cuticle act as a seal
- 0,3-0,5 mm thick
- Growth speed: 0,5-1,2 mm per week
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3) The function of the skin
The skin has major adaptive capabilities and almost live in some “symbiosis” with the external environment. When
some external insult occurs, the skin reacts to it in a way that’s most beneficial to the organism but quickly returns to
normal. If the skin fails to adapt or return to normal, skin disorders appear.
- External factors causing skin disease
o Chemical: allergens, irritants
o Physical: sunshine, heat, cold
o Mechanical: trauma, friction
o Infectious
- Internal factors causing skin disease
o Psychological factors
o Genetics
o Internal disease
o Drugs
o Infections
Primary role: barrier.

- Prevent entry of noxious chemicals and infectious organisms
- Prevent exit of water and other chemicals
- Stratum corneum prevents loss of interstitial fluid and the entry of potentially harmful substances by relative
impermeability and continuous shedding of outer keratinocytes. Passive barrier.
o Removal? → impaired barrier function
7 main functions of the skin

1) Sensation
- Mechanoreceptors – specialized end organs in dermis. Register deformation of the skin.
o Ruffini end organ → stretching
o Krause end bulbs → cold
o Meissner’s corpuscle → texture change, slow vibrations
o Pacinian corpuscle → deep pressure, fast vibrations
o Merkel’s disc → sustained touch and pressure
o Free nerve endings → heat and pain
- Thermoreceptors
- Nociceptors
- Chemoreceptors
- Most receptors are found on face and extremities
2) Heat regulation
- Blood vessels: direct heat loss (conduction)
o Skin temperature is highly responsive to skin blood flow – dilation and contraction of dermal blood
vessels cause major changes in blood flow (1-100 ml/min per 100 g skin)
o Arteriovenous anastomoses under SNS control – shunting of blood to superior venous plexus
o Local factors such as irritation
- Eccrine glands
o Sweating → heat loss by evaporation
o Max insensible perspiration per day: 0,5 L
o Maximum daily secretion: 10 L, with max output of 2 L/h
o Sweat produced in the gland is isotonic, then modified in the excretory portion
▪ End fluid: hypertonic, pH = 4-6,8
▪ Low Na+, Cl-
▪ High K+, lactate, urea, ammonia, some AA
- Subcutaneous fat → insulation
3) Absorption
- Limited
- Molecules must be sufficiently small; female sex hormones, nicotine patches, ingredients within facial
preparations
4) Protection
- Acidity of the skin discourage growth of bacteria and fungi
- Stratum corneum act as filter against bacteria
- Melanin protect against damage from UV light
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5) Excretion – only minor function

- Water
- Urea
- Ammonia
6) Secretion
- Sebum by sebaceous glands
7) Vitamin D production
- 7-dehydrocholesterol in keratinocytes converted to cholecalciferol by UV lifht
- 25-hydroxylation in liver
- 1-hydroxylation in kidney
- Kidney disease and lack of sun exposure cause vitamin D deficiency
o Fair-skinned people need less sun exposure to produce enough vitamin D compared to dark-
skinned people
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4) Protective mechanisms of the skin (skin barrier, skin immune system, UV protection)
Skin barrier
- Function: protection from water loss, noxious physical, mechanical and chemical insults. First line defense
against bacterial and viral infections. Keeping the inside in and the outside out.
- Epidermal barrier consists of the corneocytes (terminally differentiated keratinocytes) and the
intercorneocyte lipids (mortar). Defects of this mortar can for example be seen in atopic dermatitis and
psoriasis.
o Ceramides
o Cholesterol and esters
o Free fatty acids
o Phospholipids
- The cells are tightly bundled together by desmosomes and the intermediate filament network
- Contuniuos desquamation of the stratum corneum contributes to the removal of contaminants from the skin
Skin immune system

- Second line of defense if the skin barrier fails
- Cellular components of the skin immune system: keratinocytes, Langerhans cells, dermal dendritic cells, T-
lymphocytes, NK cells, mast cells
Keratinocytes:
o Prime role: protective stratum corneum
o Link between innate and aquired immune system
o Synthesize and release cationic antimicrobial peptides: cathelicidin and beta-defensin
o Carry TLR in which they can detect PAMP’s on bacteria
▪ Activation → interferon release, Th1 response
▪ Production of other chemokines → attracting other cells of the immune system →
immune response
o Injury to skin leads to IL-1 release → immune and inflammatory cascades
o Healing after injury by self-regulating epidermal proliferation and differentiation
Langerhans cells:
o In epidermis and mucous membranes
o Dendritic cells, expressing MHC-II and appropriate co-stimuli to mount a T-cell response
o Professional APC, presenting antigens to T-cells. The interleukins produced by professional APC’s
in the skin determine which path of differentiation is followed for the T-cells.
o Can also move to sentinel lymph node and induce immunity or tolerance to an antigen, depending
on the circumstances in which it’s presented
Dermal dendritic cell:

o In dermis, below basement membrane
o Activated dermal dendritic cells → cytokine secretion
o Migrate to LN → stimulation of T-cell proliferation
o Regulation of humoral Ab response
T-lymphocytes:
o Develop in thymus, differentiate into subpopulations based on their CD molecules
o CD4 – induction of immune reactions and elicit inflammation. Subtypes based on interleukins in
environment:
▪ IL-12 → Th1 → IL-2, TNF-alpha, IFN-gamma → cell mediated immunity
• Contact dermatitis
▪ IL-4 → Th2 → IL-4, IL-5, IL-10 → Ab-mediated immunity
• Atopic dermatitis
▪ IL-23, TGF-beta, TNF-alpha → Th-17 → IL-22, IL-23 → tissue inflammation, clearance of
infectious agents, autoimmune reactions and psoriasis
o CD8 – cytotoxic cells → lysing of infected, grafted or cancerous cells. Some of these are resident in
the skin and can rapidly amplify a reaction to an infectious agent without circulating to nearby LN.
Killing is mediated by granzyme B and perforin production.
o T-reg: immunosuppressive. UV radiation induce T-regs in the skin.
NK cells:
o Large granular leukocytes → granule mediated cell apoptosis or lysis
o Capable of killing infected or tumor cells without having to be sensitized
▪ Absence of MHC and Ab
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Mast cells:
o Present in connective tissue, predominantly around blood vessels
o Granules contain inflammatory mediators – histamine, for example
o Principal role in urticaria and contact allergic responses
- Molecular components of the skin immune system: antigens, superantigens, antibodies
Antigens:
o Molecules recognized by the immune system
o Immune system reacts to antigens recognized as non-self; proteins, chemicals, allografted cells,
infectious agents
Superantigens:
o Non-specific T-cell activation → massive T-cell proliferation and cytokine release
o E.g. toxic shock syndrome, guttate psoriasis
Antibodies:
o Immunoglobulins reacting with antigens. Working as opsonins to initiate immune response. Mention
the different types briefly.
o Remember that IgE is important for type I hypersensitivity reactions
Cytokines:
o Small proteins regulating amplitude and duration of immune response
o IL, IFN, cytotoxins, growth factors
UV protection
- Melanin acting as an energy sink and as free radical scavenger → absorb the energy of UV radiation. UVB
(290-320 nm) darkens skin first by photooxidation of preformed melanin and then by stimulating
melanocytes to produce more melanin.
o Eumelanin, pheomelanin
- Melanocytes make uo 5-10% of stratum basale cell population
- Melanin in melanosomes, passed on to keratinocytes through dendritic processes as they pass through the
maturation process
- Uniform distribution of melanin in stratum corneum → UV absorbing blanket → reduction of UV radiation
penetrating the skin
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5) Topical therapy in dermatology
“If it’s dry, wet it and if it’s wet, dry it”
Treatment in dermatology: topical, systemic, intralesional, radiation and surgical.
Topical therapy is targeted and have lower toxicity. The medication is directly applied to the skin, and it consists of a
vehicle (base) containing the active substance(s). Vehicles are defined as follows:
- Lotion: Liquid, alcohol or aqueous based. May contain a salt in a solution. Shake lotions contain an insoluble
powder.
o High water content allows it to evaporate → cool off the skin
o Inflamed or exudative conditions, for example wet wraps.
- Cream: Semisolid emulsion of oil-in-water. Contains an emulsifier and a preservative to prevent overgrowth
of microorganisms.
o High water content → mostly evaporate
o Non-greasy, easy to remove
o Good for wet dermatoses such as acute contact dermatitis, blistering or exudative dermatoses
- Gel: Transparent, semisolid, aqueous, non-greasy.
- Ointment: Semisolid grease or oil. Contains little or no water. No preservative needed. The active substance
is suspended rather than dissolved.
o Most suitable for dry conditions like eczema and psoriasis; rehydrate and occlude
o Doesn’t evaporate, hard to wash off; less acceptable to patients than creams
- Paste: Ointment base + high amount of powder → stiff consistency.
o Good for well-defined surfaces, like psoriatic plaques
o Hard to remove
Factors determining the ability of a drug to penetrate the skin:

- Molecular size, structure, lipid/water solubility
- Vehicle used and whether application is occluded
- Site of application; greatest absorption on genitalia and eyelid
- Whether the skin is diseased or not
How much should be prescribed?

- One application to the whole body: 15-20 g (Lange: 30 g)
- Face, neck, foot: 1 g
- Trunk (each side), leg: 3 g Tip: “fingertip unit” = 0,5 g
- Arm, hand: 0,5 g each
One week of 2x daily applied emollient: 250 g. Doctors frequently underestimate the amount needed.
- Creams/ointments are applied 2x day. Exception, 1x day: mometasone, fluticasone, tacalcitol
Topical steroids
- Effect: anti-inflammatory, antiproliferative, immunosuppressive → wide range of inflammatory skin disorders
- Potency: 1-7, where 1 is highest and 7 is lowest
o Dexamethasone – class 2
o Betamethasone – class 4-5
o Hydrocortisone – class 7
- Safe maximum amount depends on 1) strength of steroid, 2) age of patient and 3) length of treatment.
Remember that adverse effects of steroids are lower in topical administration compared to systemic.
Systemic AE typically in children treated with highly potent corticoids.
o Adult: 150-200 g/week, child: 60 g/week, babies: 20 g/week
- AE of topical corticosteroids: atrophy, telangiectasia, increased incidence of viral, bacterial and fungal
infections, delayed wound healing
- Factors in usage and selection of topical steroids
o Disease and lesion category
▪ Acute inflammatory diseases (contact dermatitis, atopic dermatitis) can be treated with
medium to high potency steroids. May need strong steroids to begin with.
▪ Highly potent steroids for treatment of chronic localized dermatoses with thick lesions,
such as psoriasis
o Localization of lesion: thin skin requires less potent steroids than thick skin
o Extent of area to be treated: larger areas → lower potency steroids
o Quantity of steroid: read package insert!
o Duration of treatment: superpotent steroids usually no more than 2 weeks. Topical steroids should
be discontinued when the rash has resolved.
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o Frequency: once or twice per day, usually

o Age of patient
▪ Children have higher ratio of TBS to body weight → higher likelihood of systemic effects.
Use low potency steroids.
▪ Low to middle potency steroids in elderly with thin, fragile skin
Topical calcineurin inhibitors: Tacrolismus, pimecrolismus

- Nonsteroidal, immunosuppressive
- 2nd line therapy in short-time therapy of moderate to severe atopic dermatitis
Moisturizers → Skin disorders where barrier function is impaired

- At least 2x day, after bathing. Therapeutic baths with emollients can also be beneficial.
- May contain ceramides, lactic acid, urea (low doses, below 20%)
o Lactic acid is topically keratinolytic and doesn’t penetrate the skin (4-10% used)
o Urea → dissolve intracellular matrix of stratum corneum, promote desquamation of scaly skin and
by that soften hyperkeratotic areas
Wet dressings
- Burow’s solution 1:40 aluminium acetate:water
- Indication: dressing for relief of inflammatory conditions of the skin like insect bites, poison ivy, allergy,
eczema, athlete’s foot
- MoA: Dry the affected area by reducing the secretory function of the skin glands.
Other topical medications:

- Antiseptics: chlorhexidine, benzalkonium chloride, potassium permanganate
o Indications: Leg ulcers, infected eczema
- Antibiotics: chlortetracycline, neomycin, bacitracin
o Indications: acne, rosacea (metronidazole), impetigo
- Antifungals: nystatin, clotrimazole, miconazole, econazole
- Antivirals: acyclovir, penciclovir
o Indications: herpes simplex, herpes zoster
- Parasiticidals: benzyl benzoate, oermethrin and malathion for scabies.
- Coal tar for psoriasis, eczema. Presumed anti-inflammatory and anti-proliferative effects.
- Vit. D analogues: calcitriol for psoriasis. Inhibit keratinocyte proliferation and promote differentiation.
- Keratinolytics: salisylic acid, benzoyl peroxide and tretinoin for acne, scaly eczemas.
- Retinoids: isotretinoin (acne), tazarotene (psoriasis)
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6) Systemic therapy in dermatology (i.e. antibiotics, antihistamines, retinoids, biologicals etc.)
Systemic treatment involves use of medication in the form of tablets or injections, which has higher potency and may
be more effective, but this must be monitored on a regular basis as there’s a risk of side effects. Systemic therapy is
mainly indicated in severe bacterial infections, acne vulgaris, preoperative preparation, severe forms of psoriasis that
doesn’t respond to topical therapy or phototherapy.
- Diseases where topical therapy is ineffective
Antibiotics
- Systemic antibiotics are indicated for acne vulgaris that doesn’t respond to topical therapy and deeper skin
infections
- Acne vulgaris – Cutibacterium acnes (formerly P. acnes)
o Moderate to severe inflammatory acne vulgaris
o Tetracyclines most commonly prescribed, but more lipophilic antibiotics such as doxycycline and
minocycline are more effective. Administered p.o.
o Systemic antibiotics commonly combined with topical benzoyl peroxide. It’s believed to reduce the
emergence of resistant strains.
o Possible side effects include vaginal candidiasis, photosensitivity and pigment deposition of skin,
mucus membranes and the skin.
- Folliculitis: presence of inflammatory cells within the wall and ostia of the hair follicle, creating a follicular-
based pustule. In superficial folliculitis it is restricted to the infundibular part of the follicle, whereas a deeper
folliculitis involves the deeper part of the follicle and extends into the deeper dermis.
o Before starting treatment, consider the etiology, severity and distribution of lesions.
o Uncomplicated, superficial folliculitis → antibacterial soap, warm compress with antimicrobial
agent.
o Deeper folliculitis → p.o. antibiotics covering gram-positive organisms
▪ Most common etiology: S. aureus
o S. aureus is commonly resistant to penicillin, so dicloxacillin or a cephalosporin can be used
o MRSA may require clindamycin, trimethoprim-sulfamethoxazole, minocycline or linezolid
- Erysipelas: bacterial skin infection involving the upper dermis, extending into the superficial cutaneous
lymphatics. Tender, intensely erythematous, indurated plaque with sharply demarcated border.
o Consideration: symptomatic treatment of fever and aches, hydration, cold compresses, elevation
and rest of affected limb
o Most common etiologic agent: streptococci
o 1st line of treatment: penicillin, p.o. or i.m., usually for 5 days to begin with
o Allergy to penicillin? 1st generation cephalosporin or clindamycin
Antihistamines
- Main indications: hay fever, allergic reactions, urticaria, puritus, eczema
- 1st generation antihistamines (anti H1): Chlorpheniramine, cyproheptadine. Sedating.
- Non-sedating H1 antagonists: cetirizine, desloratiadine, loratadine
o 1st line, dose can be increased 4 times
- H2 antagonist: cimetidine, ranitide
o CAVE: Interaction with warfarin
- Leukotriene receptor antagonist can be added as complementary treatment: monteleukast, zafirleukast
Retinoids
- Retinoids = all natural and synthetic compounds that have structural or biological activity like vitamin A
o Bind to nuclear receptor RXR, RAR of keratinocytes and sebaceous glands
o Proliferation and secretion back to normal
- Function of vitamin A: synthesis of rhodopsin, homeostasis of skin, decrease inflammation
- Retinoic drugs include acitretinoin, isotretionoin, alitretinoin etc.
- Indications: severe bullous acne, psoriasis, eczema, usually in combination with another drug like steroids,
topical vitamin D derivates, PUVA or UVB
o Acne: cumulative dose 120-150 mg/kg
o Psoriasis: start with 10 mg/day, and then increase dose as necessary
- Topical administration most common, but administered p.o. in severe cases
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Biologicals
- Biological, defined by FDA: aby therapeutic serum, toxin, antitoxin, vaccine, virus, blood, blood component
or derivative, allergenic product, analogous product or derivates applicable to the prevention, treatment or
cure of injuries or disease of man.
- General definition: protein molecules therapeutically used in various diseases to target specific points in the
inflammatory cascade of these disorders.
a) Monoclonal antibodies
- Target specific cell-surface receptors → activate a cascade or blocking action of a receptor
- Active substance can also be connected to the MAb and by that target the medication
- Adalidumab: MAb against TNF-alpha
o Psoriasis
o Hidradenitis suppurativa
- Basiliximab: MAb against IL-2
o Psoriasis
- Efalizumab: MAb against CD11a → inhibits T-cell trafficking into dermis and epidermis
o Psoriasis
o Promising in lichen planus
- Rituximab: Anti CD20. Mainly in lymphoma, but also in SLE and blistering diseases.
b) Fusion antibody proteins also known as chimeric proteins.
- Fusion of receptor domain of human protein with constant region of human IgG → binds specifically to a
ligand or co-receptor
- Denileukin diftitox: bound to IL-2, target IL-2r
o Psoriasis
- Etanercept: TNF-alpha analogue → inhibit TNF function and block pro-inflammatory effects
o Psoriasis
o Hidradenitis suppurativa
c) Recombinant human cytokines and growth factors
- Non-immunoglobulin proteins and glycoproteins produced by a wide range of cells, released in response to
immune stimulus
- Interferon alpha
o S.c. or i.m. injection
o Indications: verruca vulgaris, condyloma accuminatum, cutaneous T-cell lymphoma, Kaposi
sarcoma, melanoma, basal cell carcinoma, squamous cell carcinoma, actinic keratosis, Bechet’s
disease, hemangioma, keloids
- Interferon gamma
o Indications: chronic granulomatous disease, atopic dermatitis, cutaneous T-cell lymphoma
- IL-2
o IL-2 is an antitumor cytokine
o Indications: cutaneous T-cell lymphoma, metastatic melanoma
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7) Corticosteroids – topical and systemic therapy, indications, contraindications, side effects
Note: Oral steroids shouldn’t be used in psoriasis as they can severely flare psoriasis upon discontinuation.
Systemic steroids
- Corticosteroids taken p.o. or given i.m.
o In most patients in need of systemic steroids, p.o. administration tends to be sufficient
o Generally, a higher dose (40-60 mg/day) is prescribed at first to get in control of the skin condition,
then the dose is reduced
- Synthetic derivates of the natural steroid, cortisol
- Note that topical therapy should always be the 1st choice over systemic therapy
Mechanism of action
- Bind to cytosolic glucocorticoid receptor, activation of target genes in the nucleus → regulation of gene
expression, responsible for the effect of glucocorticoids
- Immune; generally immunosuppressive
o Up-regulate expression of anti-inflammatory proteins
o Down-regulation of proinflammatory proteins
- Metabolic
o Stimulation of gluconeogenesis
o Mobilization of amino acids from extrahepatic tissues
o Inhibition of glucose uptake in muscle and adipose tissue
o Lipolysis and fat redistribution
o Osteoclast activation
- Developmental
o Promoting maturation of lung and surfactant production in fetus
o Can cause premature closure of epiphyseal growth plate in children
Indications – generally for inflammatory conditions, as it has anti-inflammatory effect

- Acute and chronic disabling bullous disorders: pemphigus vulgaris, bullous pemphigoid
- Connective tissue diseases: SLE, dermatomyositis, Wegener granulomatosis, relapsing polychondritis
- Severe, widespread, inflammatory atopic eczema where acute control is required
o CAVE: relapse of symptoms after cessation of steroids. Monitor the patient.
- Other: severe lichen planus, pyoderma gangrenosum, Bechet’s disease, Sweet’s disease (acute febrile
neutropenic dermatosis)
Contraindications
- Allergy
- Peptic ulcer disease
- Hypertension, congestive heart failure
- Any active infection
- Diabetes mellitus
- Glaucoma
- Cushing’s disease
- Psoriasis or long term atopic eczema, as there’s a risk of rebound phenomenon
Side effects: mostly seen in long term treatment, which is generally defined as treatment lasting more than three
months. Treatment lasting a few days or weeks is relatively safe. Also, problems arise particularly when higher doses
are taken.
- Weight gain
o Mineralocorticoid effect of steroids → water retention
o Increased appetite
- Infections (fungal, viral, bacterial), reactivation of latent infections
- Hypertension, avascular necrosis
o Vasoconstriction
o Decreased vessel permeability
- Diabetes
- Osteoporosis
- Skin thinning, fragility, purpura, telangiectasia, skin striae
- Slower wound healing
- Iatrogenic Cushing: hyperglycemia, central obesity from redistribution of fat, peripheral muscle wasting,
peptic ulceration, osteoporosis, cataract, precipitation of glaucoma, hypertension, salt and water retention,
hypokalemia
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Topical steroids
Effects on the skin, when applied topically

- Vasoconstriction, decreased vessel permeability
- Decrease epidermal proliferation
- Decreased phagocytic migration and activity
- Depress fibroblast activity and fibrin formation
- Stabilize lysosomal membranes
- Inhibit cytokines
- In sum: immunosuppressive
Indications
Highly responsive – acute infl. Less responsive Least responsive
diseases
Atopic and asteatotic eczema Psoriasis – plaque (facial, flexural) Plantopalmar psoriasis
Allergic contact dermatitis Seborrheic dermatitis Discoid SLE
Napkin dermatitis Lichen simplex chronicus Chronic hypertrophic lichen planus
Subacute SLE Granuloma annulare
Popular urticaria, e.g. insect bite Keloid scars
Contraindications
- Bacterial infections; impetigo, furuncles, carbuncles, cellulitis, erysipelas
- Allergy
- Acne
- Rosacea
- Ulceration
- Relative contraindications: candida, dermatophytes, herpes simplex and zoster (antiviral is 1st line, but
glucocorticoids can be used to decrease burning and itching, as symptomatic therapy)
Cutaneous side effects

- Atrophy
- Striae
- Telangiectasia
- Easy bruising and tearing of the skin
- Localized increased hair thickness and length (hypertrichosis)
- Potent topical steroids administered over long period of time can lead to periorificial dermatitis and steroid
rosacea. Rebound flare can occur upon discontinuation of the drug.
- Note that systemic absorption can occur and thus also systemic side effects. Risk increase with increasing
dose and duration of therapy.
Potency of topical steroids

- Very potent (600x): hydrocortisone-betamethasone dipropionate
- Potent (100-150x): betamethasone, methylprednisolone
- Moderate (2-25x): clobetasone, triamcinolone
- Mild: hydrocortisone
Formulation
- Ointments → dry, non-hairy skin
o No requirement for preservative, reducing risk of irritancy and contact allergy
o Occlusive → risk of folliculitis and miliaria
- Gel or solution → hair-bearing skin
o Astringent (drying) effect
o Stings inflamed skin
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8) Essential principles of local treatment
Percutaneous absorption
- Active substance must be dissolved/suspended in a vehicle to be absorbed
- Rate-limiting step: the transfer of drug from the vehicle to stratum corneum
- Penetration of drug depends on the following factors:
o Concentration and concentration gradient
o Molecular weight of molecule
o Duration of contact
o Solubility of medication: lipophilic > hydrophilic
o Physical condition of the skin: hydration, blood flow, temperature of skin
o Part of the body exposed including amount of hair on the skin
- Absorption, fastest to slowest: scrotal > forehead > armpit > scalp > back and abdomen > palm > under foot
Vehicles
- Lack primary chemical or pharmacological action, act primarily as physical bases to carry the active drug
- Physically and chemically stable alone
- With drug should be nonirritating, nonallergenic, cosmetically acceptable and easy to use
- Must be able to release the drug from the topical preparation to the desired site in the skin
- Can have drying or hydrating properties
- Mixture of water, grease and powders with added stabilizers, emulsifiers, preservatives
- Dusting powders – Talc, starch. Used in skin folds to lesser friction and irritation. Don’t use it in wet areas
due to caking of the powder.
- Watery lotions – Evaporate and cool inflamed areas. Faster evaporation by alcohol, slower evaporation by
glycerol.
- Shake lotions – Water and powder mix. Area of evaporation is increased. Has good drying properties and
used on wet areas. Water will evaporate and leave the powder behind, which may clump together.
- Cream – Cooling, moisturizing and emollient effects.
- Ointment – Occlusive and emollient properties. Prevent water from evaporating.
- Gel – Hydrophilic or hydrophobic. Suitable for scalp application, individual lesions and when greasy vehicles
aren’t appropriate.
- Paste – Protective and emollient. Powder makes the grease “breathe”.
Amount needed
- Full adult body: 250 g/week
- 12 y – 185 g/week
- 8 y – 130 g/week
- 4 y – 80 g/week
Dressings → protect open lesions, facilitate healing, increase drug absorption and protect clothing
- Nonocclusive dressings: gauze dressings most commonly, maximally allowing air to reach the wound,
allowing the lesion to dry
o Wet-to-dry dressings are nonocclusive dressings wetted with solution → cleanse and debride
thickened or crusted lesions. Removed when the solution has evaporated with materials from the
skin adhering to the dried dressing.
- Occlusive dressings → increase absorption and effectiveness of topical therapy
o Polyethylene wrappings
o Hydrocolloid dressings
o Zinc oxide gelatin (Unna paste boot) for stasis dermatitis and ulcers
Categories of topical agents

- Cleansing: Soaps, detergents, solvents. Useful for removing crusts and scales in eczema, psoriasis.
Shouldn’t be used for acutely irritated, weeping or oozing lesions (water or isotonic saline is preferred).
- Moisturizing: Emollients restore water and oils to the skin, help maintain hydration. Typically contain
glycerine or mineral oil. Stronger moisturizers contain urea 2%, lactic acid 5-12% and glycolic acid 10%.
- Drying: Excessive moisture in intertriginous areas can cause maceration and irritation. Powders useful to dry
these areas by absorbing moisture and by that also reduce friction → less irritation.
- Anti-inflammatory: Corticosteroids, tar, herbal products.
- Antimicrobial: Antibiotics, antifungals, insecticides.
- Keratolytic: Salicylic acid to treat psoriasis, seborrheic dermatitis, acne, warts.
- Astringent: Drying agents that precipitate protein, shrink and contract the skin. Most commonly used are
aluminium acetate (Burow solution). Usually applied with dressings or as soaks.
- Antipuritic: Doxepin (topical antihistamine), camphor, menthol, EMLA.
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9) Terminology of skin lesions, distribution of exanthemas
Key features of skin lesions

- Type of lesion
- Secondary changes to the surface of the lesion
- Colour of the lesion
- Shape of the lesion
- Arrangement and distribution
o Symmetric/asymmetric
o Unilateral/bilateral
o Diffuse/grouped
! mouth, scalp and nails shouldn’t be overlooked !
Primary lesions – appear as a direct result of a disease process. When examining a dermatological patient, try to find
an early primary lesion to examine, as older lesions can have altered morphology due to irritation, scratching,
ulceration or change from other events.
Small (<5mm) Large (>5mm)

Flat area of altered colour or Macule Patch
texture
Elevated solid elevation Papule (dome-shaped, Nodule (>5mm in with and
pedunculated, verrucous, depth)
umbilicated, flat-topped, Plaque (>2cm in with but
acuminate) without substantial depth)
Fluid-filled blister Vesicle Bulla
Pus-filled blister Pustule Abscess (Ø>1cm)
Furuncle
Extravasation of blood into Petechia (pinhead size) Ecchymosis
skin Purpura (up to 2 mm) Haematoma
Accumulation of dermal Wheal (can be any size) Angioedema
oedema
- Macule: change in surface colour, without elevation or depression. The macule can be brown, red, blue or
hypopigmented. Not palpable.
- Patch: large macule. Patches can have subtle surface changes (fine scale, wrinkling), but generally not
palpable.
- Papule: circumscribed, solid elevation of skin with no visible fluid. For example nevi, wart or seborrheic
keratoses.
- Plaque: broad papule or confluence of papules with a well-defined border. Can be seen in psoriasis, lichen
planus and tinea corporis.
- Nodule: similar to papule, but it’s larger and extends deeper into the dermis or subcutis. Examples can be
hemangioma, basal cell carcinoma and neurofibromatosis. Nodules can be endophytic or exophytic.
- Vesicle: small blister, well-circumscribed. Contains clear serous fluid.
- Bulla: large blister, sounded or irregularly shaped. For example blisters of bullous pemphigoid and
pemphigus vulgaris.
- Pustule: small elevation of the skin containing purulent material.
- Abscess: larger collection of pus.
- Furuncle: also known as a boil. Painful infection around a hair follicle, containing pus.
- Ecchymosis: larger extravasation of blood into the skin and deeper structures.
- Haematoma: swelling from gross bleeding.
- Angioedema: diffuse swelling caused by edema extending into the subcutaneous tissue.
Secondary lesions (surface changes) – result from changes in primary lesions. Can also be created by scratching or
infection.
- Scale: thickened stratum corneum. Dry and usually whiteish, can be seen on the surface of many primary
lesions.
- Crust: liquid debris (dried pus or blood). In contrast to the white scales, crusts tend to be yellowish or brown.
- Keratosis: horn-like thickening of stratum corneum.
- Fissure (crack, cleft): linear cleft through the epidermis, extends into the dermis.
- Ulcer: an area of skin from where the whole epidermis and at last the upper part of dermis has been lost.
May extend all the way into the subcutaneous fat and heals by scarring.
- Erosion: loss of whole or parts of the epidermis only. Dermis is not affected. Heal without scarring.
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- Excoriation (scratch marks): abrasion (ulcer or erosion) produced by mechanical force. Usually involves the
epidermis, but upper layers of the dermis can also be affected.
- Necrosis: dead skin tissue.
- Eschar: black hard crust due to tissue necrosis of epidermis/dermis.
- Skin atrophy: thinning of the skin due to loss of epidermis, dermis or subcutaneous fat. The skin appears
wrinkled, translucent and with easily visible blood vessels.
- Scar: result of healing were normal tissue is replaced by fibrous connective tissue at the site of an injury
(keloid: elevated and progressive scar not showing regression).
- Stria: streak-like linear atrophic pink, purple or white lesion of the skin caused by connective tissue changes.
- Lichenification: area of thickened skin with increased markings. Result of rubbing or scratching.
- Pigmentation: either more or less than the surrounding skin. Can develop when lesions heal.
When the lesions are defined as either primary or secondary, they can be further described in terms of the following:
- Color
- Sharpness of edge: defined x ill-defined
- Surface contour: dome-shaped x umbilicated x spire-like
- Geometric shape: nummular, oval
- Texture: rough x silky x smooth x hard
- Smell: foul-smelling
- Temperature: hot, warm
Dermatologists use different terms to describe a lesion:

- Nummular: round or coin-like
- Annular: ring-like
- Circinate: circular
- Arcuate: curved
- Discoid: disc-like
- Grytate: wave-like
- Retiform and reticulate: net-like
- Targetoid: target-like, or bulls-eye
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10) Distribution and patterns of skin lesions
It’s important to note:

- Single x multiple
- Affection of specific body parts (palms or soles, scalp, mucosal membranes)
- If the distribution is random or follows a pattern
- Symmetric x asymmetric
- On sun-exposed skin
Depending on the disease suggested by the morphology, you may want to check specific areas.
- Feet in a patient with hand eczema
- Gluteal cleft in a patient who might have psoriasis
- Does it affect flexures (atopic eczema) or extensors (psoriasis)?
- Dermatomal distribution?
Remember to examine as much of the skin as possible! Don’t forget to examine the mouth, hair and nails too.
Typical distribution of common skin diseases:

- Face: acne, rosacea, SLE, non-melanoma skin, cancer
- Scalp: psoriasis, seborrheic eczema, lichen planus, atopic eczema, fungal infections, lice
- Mouth: herpes simplex, lichen planus, apthous ulcers, immunobullous conditions, candidiasis/angular
cheilitis
- Elbows:
o Extensor: psoriasis
o Flexor: eczema
- Hands: psoriasis, eczema, actinic keratosis, scabies
- Nails: psoriasis, lichen planus, fungal infections
- Umbilicus, natal cleft: psoriasis
- Genitals: flexural psoriasis, seborrheic eczema, lichen sclerosus, intertrigo, fungal infection, genital warts,
pubic lice, scabies
- Knees:
o Extensor: psoriasis
o Flexor: eczema
- Lower legs: small vessel vasculitis, gravitational eczema
Some patterns are consistent with certain diseases:

- Psoriasis – scalp, extensor surfaces of elbows and knees, umbilicus, gluteal cleft
- Lichen planus – wrists, forearms, genitals, ankles
- Vitiligo – patchy and isolated or grouping around distal extremities and face. Particularly around eyes and
mouth.
- SLE – characteristic lesions on sun-exposed skin; forehead, nose, conchal bowl of the ear.
- Hidradenitis suppurativa – skin containing a high density of apocrine glands; axillae, groin, under breasts.
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11) Simple diagnostic tests (Auspitz phenomenon, dermographism, Nikolsky test, Darier’s sign, Köbner’s
phenomenon, Tzanck’s test etc.)
Auspitz phenomenon
The appearance of punctate bleeding spots when psoriasis scales are scraped off. Happens due to thinning of the
epidermal layer overlying the tips of the dermal papillae and blood vessels within the papillae are dilated and torturous,
which bleed easily when the scale is removed.
Dermographism
Appearance of an urticarial wheal after focal pressure (e.g. stroking or scratching the skin) in the distribution of the
pressure. Caused by the histaminoliberation from mast cells in the skin. The membrane of the mast cells is too weak
and will easily and rapidly break down under physical pressure. Dermographism is sometimes called “skin writing”.
Nikolsky test
Epidermal shearing/exfoliation of the outermost layer that occurs with gentle lateral pressure on seemingly uninvolved
skin in patients with toxic epidermal necrolysis (Steven-Johnson’s syndrome) and some autoimmune bullous diseases.
- Pemphigus vulgaris: nikolsky positive
- Bullous pemphigoid: nikolsky negative
Darier’s sign
Rapid swelling of a lesion when stroked. Seen in patients with systemic mastocytosis or urticaria pigmentosa, diseases
in which mast cells are hyperactive. The skin becomes swollen, itchy and red as a result of mast cell compression.
The mast cells release inflammatory granules, which contain histamine → skin lesions.
Köbner’s phenomenon
Describes the development of lesions within areas of trauma such as scratching, rubbing or injury. Psoriasis frequently
exhibits this phenomenon, or lichen planus, often resulting in linear lesions.
- Have the same clinical and histological features as lesions of the patient’s original skin disease
- Are not due to the seeding of an infectious agent, an allergic reaction or due to skin breakdown
- Mainly associated with psoriasis and lichen planus, but also with vitiligo, mollusucum contagiousm,
pyoderma gangrenosum, warts
Tzanck’s test (or Tzank smear)

The scraping of an ulcer base to look for Tzanck cells (multinucleated giant cells) found in herpes simplex, varicella,
herpes zoster, CMV, pemphigus vulgaris. The blister roof is removed and cells from the base of the blister are scraped
off and smeared onto a microscope slide, air-dried and fixed with methanol. Stained with Giemsa, toluidine blue or
Wright stain. This technique has fallen out of favour as histology, virology culture and PCR has become more
accessible.
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12) Diagnosis – techniques – and laboratory tests of skin diseases
Special tools and techniques

- Magnifying lens to visualize subtle changes
- Wood’s light
o Examination of skin or hair with lamp emitting black light
o Blacklight is in the UV-spectrum (10 – 400 nm)
o Fluorescence is seen in some fungal infections, erythrasma and pseudomonas infections
o Can be used to determine whether pigmentation is epidermal (enhanced by Wood’s light) or dermal
(unchanged)
o Low-grade vitiligo can be seen better
o Porphyria causes red-pink fluorescence
- Diascopy
o Glass slide or clear plastic spoon is pressed on vascular lesions to blanch them
o Verify that the redness is actually caused by vasodilation and to unmask underlying colour
o Petechia and purpura for example will not change on pressure
o Useful in diagnosis of granulomatous condition (sarcoid) → reveals colour reminiscent of apple jelly
- Dermoscopy, also called epiluminoscopy and epiluminescent microscopy
o Non-invasive
o Skin examination by using skin surface microscopy
o Most frequently used to evaluate elevated pigmented skin lesions, melanoma
o Also used for diagnosis of scabies
- Photography
o Record baseline appearance of a skin lesion or rash
o Objective assessment of changes at a later point
Side-room and office tests (results will be available immediately)

- Potassium hydroxide preparations → used to differentiate dermatophytes and candida albicans symptoms
from psoriasis and eczema
o Scales or plucked hairs can be dissolved in an aqueous solution of 20% potassium hydroxide
(KOH) and 40% dimethyl sulfoxide (DMSO)
o Scale from edge of scaling lesion can be scraped onto a slide
o Other samples can be nail clippings, roof of blisters, hair pluckings, content of pustules
▪ A drop or two of KOH to run under the coverslip. If only KOH is used, it must be heated.
With DMSO, no heat is needed.
o 5-10 minutes to dissolve skin cells, hair and debris → examination under microscope with
condenser lens to visualize the fungi
- Bacterial swabs of wounds/rashes that are smelly, weeping, crusting or with yellow (S. aureus) or green
(Peudomonas) discoloration
o Bacterial culture and sensitivity
o Empirical treatment usually given, but slow response to the treatment → swab
o Identification of etiologic agent and appropriate antibiotic
▪ Important to limit the use of broad-spectrum antibiotics and prevent resistance
development
- Detection of scabies mite
o Burrows in an itchy patient = diagnostic of scabies
o Retrieving a mite from the skin confirms the diagnosis
o Dermoscope to visualize the burrow: the mite should be present at the end of the least scaly,
newest part of the burrow
o Mite removed by a sterile needle and put on a slide
o If mites are not seen, the burrows can be scraped with a 15 blade scalpel, moistened with liquid
paraffin or vegetable oil, and the scrapings transferred to a slide
- Cytology, Tzanck smear (Q11)
- Patch test → detection of allergens causative of contact dermatitis
o Application of a chemical to the skin, leaving it there and observing 48-96h later
o Testing of suspected antigens or a battery of antigens that are common can be tested. Applied to
the back under aluminium discs or patches.
o Patches are left in place for 48h and then after careful marking removed
▪ Sites inspected 10 minutes later and again 2 days later
o Be careful with which antigens are tested in atopic individuals as it can cause sensitization to the
particular antigen and thus a reaction upon subsequent exposures
o Detection of type IV delayed hypersensitivity reactions
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o Readings are scored according to the reaction seen:

▪  doubtful reaction (minimal erythema)
▪ + weak positive reaction (erythema and maybe papules)
▪ ++ strong reaction (palpable erythema and/or vesicles)
▪ +++ extreme reaction (intense palpable erythema, coalescing vesicles and/or bullae)
▪ IR irritant reaction (variable, but often sharply circumscribed with a glazed appearance
and increased skin markings)
o Positive reaction doesn’t necessarily mean that the allergen in question has caused the current
episode of contact dermatitis. The results must always be interpreted in light of the history and
possible previous exposure to the allergen.
- Prick testing
o Detects type I hypersensitivity reaction, so patients shouldn’t have taken systemic antihistaminics
for at least 48h before the test
o Commercially produced diluted antigens and a control placed on the skin as single drops on the
forearm
o Drops are gently pricked through using a new sterile fine needle. The prick shouldn’t cause
bleeding! Drops are wiped off with a clean tissue after.
o Sites are observed 10 minutes later → wheal 4mm or larger is considered positive and the control
elicits a negative reaction
o Always be aware of the risk of anaphylaxis (rare, but can happen), so adrenaline and oxygen
should be available
- Skin biopsy – surgical removal of a piece of skin
o Incisional – only part of lesion is removed
o Excisional – whole lesion is removed, preferable for most small lesions
o Should ideally involve a part of the surrounding healthy skin
- Scapel biopsy
o Provide more tissue than a punch biopsy
o Routinely used, but especially useful for examination of the subcutaneous tissue
o Elliptical piece of skin, including subcutaneous fat, is removed
o Suturing of the wound
▪ Legs and back: 3/0. Removal in 10-14 days.
▪ Face: 5/0. Removal in 4-7 days.
▪ Elsewhere: 4/0. Anterior trunk and arms, sutures removed in 7-10 days.
- Punch biopsy
o Hard to obtain a specimen including healthy skin by using punch biopsy
o Cylinder of skin incised with the punch by rotating it back and forth
o Base cut at the level of subcutaneous fat
o Defect cauterized or stitched with a single suture
Laboratory tests
- Hematology
o Neutrophilia – infection, severe inflammatory disorders like generalized pustular psoriasis, Sweet
syndrome, pyoderma gangrenosum
o Lymphocytosis – viral infections, tuberculosis, syphilis
o Renal, hepatic, thyroid and iron evaluated in generalized puritus, vasculitis or systemic symptoms
o Antinuclear and extractable nuclear antigen antibodies and tissue autoantibodies in patients with
suspected connective tissue or autoimmune disease
o Specific serology: HBV, HCV, HIV, syphilic
o Immunoglobulins, cryoproteins, complement – vasculitis, connective tissue disease
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13) Anaphylactic shock, Hoigne syndrome
Anaphylactic shock
- Definition: Acute, potentially fatal, multiorgan system reaction caused by the release of chemical mediators
from mast cells and basophils. The classic form involves prior sensitization to an allergen with later
reexposure, causing symptoms via an immunologic reaction.
- Clinical presentation → cutaneous, respiratory, carciovascular and GI systems. Adults present more often
with a combination of urticaria, erythema, puritus and angioedema, whereas children may present more
commonly with respiratory symptoms, followed by dermatologic symptoms. Mechanism not fully understood.
o Dermatologic: flushing, urticaria, angioedema, cutaneous and/or conjunctival injection or puritus,
warmth, swelling
▪ Urticaria often localized at palms, soles and inner thighs, associated with intense puritus
▪ Angioedema = soft tissue swelling. Nonpuritic, nonpitting. Commonly involve larynx, lips,
eyelids, hands, feet and genitalia.
o Respiratory: nasal congestion, coryza, rhinorrhoea, sneezing, throat tightness, wheezing, stridor,
shortness of breath, cough, hoarseness, dyspnea
o Cardiovascular: dizziness, weakness, syncope, chest pain, palpitations
o Gastrointestinal: dysphagia, nausea, vomiting, diarrhoea, bloating, cramps
o Neurologic: headache, dizziness, blurred vision, seizure (rare)
o Other: metallic taste, feeling of impending doom
- Diagnosis: Primarily a clinical diagnosis! Prioritize to assess airways, breathing and circulation, as well as
adequacy of mentation.
- Etiology
o Most commonly foods and i.v. administered contrast agents
o Insect bites, medication (beta-lactam antibiotics, aspirin, NSAIDs)
o Other atopic diseases such as asthma, eczema and allergic rhinitis are risk factors for anaphylaxis
- Pathophysiology
o Immunologic
▪ Sensitization to an antigen and production of antigen-specific IgE
▪ Reexposure to antigen → IgE cross-link to mast cells and basophils
▪ Release of inflammatory mediators such as histamine
o Non-immunologic
▪ Substances that directly cause degranulation of mast cells and basophils, such as
contrast medium, opioids, temperature and vibration
o Mechanism
▪ Release of inflammatory mediators → smooth muscle spasm in respiratory and GI tract,
vasodilation, increased vascular permeability and stimulation of sensory nerve endings
▪ Increased mucus secretion, increased bronchial smooth muscle tone, airway edema →
respiratory problems
▪ Vasodilation and increased permeability → hypotension, cardiac arrhythmias, syncope
and eventually shock if left untreated
• Distributive shock
- Treatment, management
o ABC-evaluation, monitor vital signs
o Oxygen
o Epinephrine – primary treatment!
▪ i.m. administration
o Antihistamines and steroids (dexamethasone) as adjunct therapy
o Bronchodilators (salbutamol)
o Patients with severe anaphylaxis (with cardiovascular and/or severe respiratory symptoms) should
be admitted or treated and observed for a longer period in the emergency department or an
observation area
Hoigne’s syndrome
- Pseudoanaphylactic or pseudoallergic reaction occurring after intramuscular administration of depot
procaine or penicillin G
- Usually embolic-toxic reactions, possibly due to vascular occlusion by large crystals of the penicillin salts
- Caused by possibly accidental i.v. administration resulting in microembolization to the brain and lungs
- Characterized by fear of impending death, fear, confusion, agitation, halluscinations or fits immediately after
injection
- No signs of circulatory collapse
- Lasts less than 20 minutes, starts seconds/minutes after injection
- Reversible, doesn’t require treatment
- Ddx. anaphylaxis
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14) Basic types of immunologic reactions (principles, examples): hypersensitivity reactions on the skin
Mechanical barrier
- Defensins present in epidermis → prevent bacterial replication by disruption of membrane
- Activation of complement cascade by alternate pathway yielding lytic complex, C5a- and C3b-chemotaxins,
C5b-opsonin
- Keratinocytes can produce cytokines leading to proliferation and shedding upon trigger from chemicals,
such as detergents
- Langerhans cells are APC’s, recognizing PAMPs
Adaptive immune system

- Specific and long lasting
- Memory cells remain in dormant state and are ready to react quickly and powerfully when reexposed to the
same antigen that stimulated their proliferation
- Antigen-specific antibodies circulate
Type I hypersensitivity
- IgE mediated
- Responsible for allergies, hypersensitivity reactions
- Mechanism
o Sensitization to allergen
▪ Allergen binds to B-cells, which is presented to a Th2 cell
▪ The T-cell will release IL-4 and IL-13 → stimulating the B-cell to undergo class switching
to produce IgE
o The antigen specific IgE produced by the B-cell attach to the Fc receptor on mast cells and
basophils. Mast cells and basophils are the effector cells of type I hypersensitivity reaction.
▪ IgE alone in the serum has short half-life, but not when bound to a mast cell, there it can
remain for months, years (“loaded gun”)
o Reexposure → cross-linking of bound IgE → stimulation of degranulation
▪ Primary mediators – pre-made, stored in granules
• Histamine → smooth muscle contraction, increased vascular permeability
• Heparin → anticoagulant
• Eosinophil chemotactic factor → eosinophil recruitment
▪ Secondary mediators – mediators must be produced, so effect only in later stages
• Prostaglandins D2, E2, F2alpha → same as histamine
• Leukotriene C4, D4, E4 → same as histamine
• Leukotriene B4 → neutrophil chemotactic factor
o Later, eosinophils will be recruited by the inflammatory response
o Rapid response
- Effects of mast cell and basophil degranulation → inflammatory reaction
o Increased vascular permeability
o Inflammation
o Bronchoconstriction
o Intestinal hypermotility
o Tissue damage
- Examples
o Urticarial reaction – vasodilation, edema, inflammation
o Hives as a reaction to food
Type II hypersensitivity
- Humoral cytotoxic type; when IgM or IgG bind directly to skin or tissue
- Type II cytotoxic → complement activation through classic pathway
o When there’s a cytotoxic reaction that damages the tissue
o Normally react to bacteria, but also involved in autoimmune diseases such as pemphigoid where
IgG bind to basement membrane between epidermis and dermis
▪ Hemidesmosome autoantibodies
- Type II non-cytotoxic
o When the antibodies change the function of the organ, for example Grave’s disease
o Not very relevant in dermatology
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Type III hypersensitivity

- Complex-mediated type. Antigen + antibody create a complex which activates the complement system.
o More systemic since the immune complexes are circulating, and wherever they settle, you will have
a reaction
- How? Activate complement, recruit inflammatory cells, damage the tissue
- SLE → nephritis, arthritis, vasculitis, butterfly facial rash
- Vasculitis
- Arthus reaction – local pain and edema as a reaction to any injected protein into the dermis
o Antigen react with antibody in the vessel wall → local complement activation
o Chemotaxis of leukocytes, damage to vessel wall and extravasation
Type IV hypersensitivity
- Delayed type (48-72h), the only one mediated by T-cells (CD4+)
- The inflammation cause recruitment of macrophages and other cells into the affected tissue
- Common in chronic intracellular infections
- Mechanism
o 1st exposure to antigen → antigen trapped on the membrane of Langerhans and dendritic cells
o Langerhans and dermal dendritic cells migrate to afferent lymphatic and process the antigen
o Once the APC has arrived in the lymph node, the antigen is re-expressed on the surface of the
APC → interaction with naïve T-cell → production of clone of memory T-cells (CD4+)
o Reexposure of antigen: antigen is again caught by Langerhans cell and dermal dendritic cells,
processed and presented on the surface
o Antigen is recognized by memory cells
o Interaction between antigen, APC and lymphocyte → cytokine release
o IFN-gamma → activation of endothelium to capture lymphocytes in blood vessel
o Chemokines → chemotaxis
o IL-2 → activation and recruitment of bystander lymphocytes
o Inflammatory cells (mostly T-cells) accumulate in dermis and epidermis, leading to destruction and
removal of antigen
- Antigen can be for example nickel or a hapten bound to a self-molecule
Granuloma
- When antigen isn’t entirely removed, a granuloma can be formed → “enclosing” and “dearming” the antigen
by containing it inside a granuloma
- Seen in leprosy, tuberculosis, leishmaniasis
- Similar non-caseating granuloma seen in sarcoidosis
- Macrophages differentiate into epithelioid giant cells, which together with outer lymphocytes create a wall
between the inflammation and normal tissue
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15) Phototherapy – principles

19) Phototherapy – methods, indications, contraindications
Basics
- Phototherapy is the use of ultraviolet radiation Skin type classified by their reaction to ultraviolet light
or visible light for therapeutic purposes Type Definition Description
- In use today: narrowband and broadband I Always burns, never tans Pale skin, red hair,
UVB, psoralen photochemotherapy (PUVA), freckles
UVA1 phototherapy, targeted phototherapy II Usually burns, sometimes tans Fair skin
- Visible light: 390 (violet) – 700 (red) nm III May burn, usually tans Darker skin
- UV-spectrum
IV Rarely burns, always tans Mediterranean
o UVA: 320 – 400 nm, can reach mid-
or lower dermis and thus more V Moderate constitutional Latin American,
effective than UVB for diseases pigmentation middle eastern
VI Marked constitutional pigmentation Black
where the cutaneous pathology is
deeper than the superficial dermis
▪ Production of UVA-induced oxidants, resulting in DNA damage, lipid peroxidation, protein
damage, organelle damage
▪ Can create pyrimidine dimers in DNA, but less effective than UVB in doing so
o UVB: 290 – 320 nm, absorbed by epidermis and superficial dermis
▪ Produce DNA damage; pyrimidine dimers and pyrimidine-pyrimidone photoproducts
▪ Photochemical changes in trans-urocanic acid → converted to cis-form
▪ Cis-urocanic acid (breakdown product of histidine) is a mediator of UVB-induced
immunosuppression
o UVC: < 290 nm
o Penetration is inversely proportional to wavelength
- Interaction between skin and photons depends on the amount of photons reflected, scattered and absorbed
- Absorption is the transfer of energy from light to tissue
- Different chromophores absorb photons selectively depending on their absorption profile or spectrum. They
determine the extent that light penetrates the skin as a photon absorbed isn’t capable of penetrating the skin
anymore.
o Energy from light passed on to chromophore → heat, drive photochemical reactions
o Chromophores: haemoglobin, water, melanin, tattoo pigments, photosensitising drugs (psoralen)
- Effects of phototherapy on the immune system
o Effective in diseases where T-cell hyperactivity predominates: psoriasis, atopic dermatitis, lichen
planus
o UVB inhibit activation of effector T-cells → equilibrium of effector and regulatory T-cells leaned
towards a diminished cell-mediated response
o Increased IL-10 have been found after UVB, UVA1 and PUVA → diminish capacity of dendritic cells
to present antigen to effector T-cells and thus suppress T-cell responses
- Phototesting prior to treatment → determine starting dose. Aim is to have minimal or no erythema 24h (UVB)
or 48h (PUVA) after irradiation.
- Careful recording of cumulative dose
Ultraviolet radiation therapy

- Controlled trials have shown that UVB helps conditions like chronic plaque psoriasis, atopic dermatitis,
ptyriasis rosea and cutaneous T-cell lymphoma
- Open trials show that UVB can improve even acne, nummular eczema, neurodermatitis, some types of
vitiligo, cholinergic urticaria etc.
- UVB is also effective in desensitizing patients with some photodermatoses; polymorphic light eruption and
solar urticaria
- Result is cutaneous immunosuppression
- Minimal long-term side effects compared to strong steroids
o Major long-term side effect remains skin carcinogenesis
o Proper dosimetry necessary to prevent sunburn and blistering
- Broadband UVB is still used in some situations, but narrowband UVB and PUVA are the two main categories
of phototherapy today
Side 25 av 31
Narrowband UVB (311 nm) therapy

- Most common form of phototherapy to treat skin diseases
- Compared to broadband UVB:
o Shorter exposure time, but higher intensity
o Shorter course of treatment
o Higher likelihood of clearing the skin condition
o Longer periods of remission before recurrence
- Indications: psoriasis, ptyriasis lichenoides chronica, ptyriasis rosea, vitiligo and puritus in renal failure
PUVA (320-400 nm) + psoralens

- Psoralen photosensitizers are activated by UVA radiation
- Psoralen administered p.o. or topically
o Opaque sunglasses must be worn 24h after taking psoralen
- Depth of penetration: mid-dermis
- Major photochemical effect is damage to DNA, and the changes differ from those of UVA and UVB without
psoralens
- Psoralens have two double bonds that can absorb UVA radiation, and when administered to an individual,
these compounds intercalate with DNA
- Following UVA exposure, they form a single adduct with DNA and then become a bifunctional adduct, cross-
linking the DNA strands in the double helix when a second photon in absorbed
- It augments the production of reactive oxygen intermediates such as singlet oxygen → induction of COX
enzyme and activation of arachidonic acid pathways
- Essentially the photoconjugation of psoralens to DNA causes subsequent suppression of mitosis, DNA
synthesis and cell proliferation. Beneficial to revert the increased cell proliferation seen in psoriasis back to
normal.
- Advantages of PUVA
o The most effective of the available phototherapy options
o Low carcinogenic risk
o Rays of UVA penetrate deeper into the skin
- Indications: psoriasis, mycosis fungoides (patch stage and plaque stage), vitiligo, severe atopic dermatitis,
ptyriasis lichenoides et varioformis acuta, ptyriasis lichenoides chronica
- Contraindications
o Absolute: xeroderma pigmentosum, SLE, breast-feeding
o Relative: pregnancy, children under 12 years, immobility/inability to stand for 10 minutes or longer,
very fair skin (skin types I + II), photosensitizing creams/medication, severe cardiac, hepatic or
renal diseases, history of skin cancers, cataracts, immunosuppressed patients
- Immediate effects: excessive erythema, puritus, nausea (methoxsalen)
- Long term effects: pigmentation, cataract, premature skin aging, potential carcinogenesis
UVA1 phototherapy
- 340-400 nm
- Penetrate more deeply into the skin than UVB
- Induce T-cell apoptosis
- Reduce number of mast cells and Langerhans cells
- Increase collagenase expression
- Tanning
Photodynamic therapy (PDT)

- Incorporation of photosensitizer in target tissue and then activating it with laser or non-laser light source
o Most commonly: porphyrin precursor 5-aminolaevulinic acid + irradiation with red light
o ALA applied topically under occlusion for 2-4h → → metabolized in haem biosynthesis pathway
o Light exposure for 15-60 minutes
o Activated protoporphyrin IX converts molecular oxygen to singlet oxygen and free radicals →
ischemic necrosis of target tissue by damaging cell walls, especially in blood vessels
- Indications: actinic keratoses, Bowen’s disease, superficial BCC less than 2 mm thick
- Advantages
o Non-invasive
o Ability to treat any lesion at once
o Rarely cause ulceration, good cosmetic result
o Good patient acceptability
o Useful for tumour treatment
Side 26 av 31
Laser therapy (light amplification by the stimulated emission of radiation)

- High intensity coherent beam of light, of a specific wavelength
- Laser → absorbed by chromophore (tattoo pigment, melanin in hair, oxyhaemoglobin in blood vessels) →
local/microscopic tissue destruction depending on the following:
o Energy
o Duration of pulse
o Thermal relaxation time
- Mechanism of action of different lasers
o Photothermal: light is absorbed by chromophore and converted to heat → coagulation of
vapourization
▪ Cont. lasers: non-selective damage
▪ Pulsed lasers: selective damage
o Photomechanical: beam of light delivered fast for a few nanoseconds → mechanical damage to
subcellular organelles containing melanin or other pigment
o Photochemical: laser light triggers a chemical reaction
- Indications: port-wine stains, tattoos, epidermal naevi, pigmented lesions, seborrheic keratoses, warts,
tumours, melasma, unwanted hair
- Absolute contraindications: use of isotretinoin within the previous year, concurrent bacterial or viral skin
infection, ectropion
- Dark skin must be treated with care as pigment irregularities can occur
Side 27 av 31
16) Physical therapy in dermatology
Surgery
- Skin surgery becomes more and more common
- Preparation
o Should be performed in designated rooms with appropriate facilities, except for bedside biopsies in
unconscious patients or patients that are too ill to move
o Standard biopsies can be preformed with clean gloves and isopropyl alcohol prep on the skin
o Excisions and Mohs’ reconstruction should be performed with antiseptic prep (chlorhexidine or
iodine prep), sterile gloves and sterile equipment
o Local anaesthetic: lidocaine 1-2% with epinephrine
o Antibiotic prophylaxis isn’t recommended for simple skin surgery, but should be used in high risk
patients where the risk of wound infection is 5-15%
Skin biopsy
- Shave or punch techniques – only in epidermis and dermis
- Inscisional/excisional biopsy – reach all the way to subcutaneous tissue
- See Q12
Excision
- Local anaesthetic, aseptic technique
- Removal of small tumours
- The area of excision must be carefully examined to avoid damaging of important structures like vessels and
nerves
- The cut should ideally run along a line of natural skin crease, especially on the face
- The incision should be in the shape of an ellipse with a margin of normal skin, where the width of that margin
varies depending on what type of lesion it is. The length should be 3-4x the with to minimize the formation of
“dog ears” when closing the wound. Make sure to hold the scalpel perpendicular to the skin.
o Benign lesions: 1-2 mm
o BCC, SCC: 4-5 mm
o Atypical naevi: 3-4 mm
- Incision should reach subcutaneous fat
- Subcutis and dermis should be closed with absorbable sutures
- Epidermis closed with non-absorbable interrupted sutures
- Removal of stitches
o Face: 5-7 days
o Trunk and limbs: 10-14 days
Shave excision
- Only for benign exophytic lesions
o Some cells are left at the base, so with malignant lesions, the risk of recurrence is high
- Lesion removed by scalpel tangential to the skin
Saucerization excision
- Deeper variant of the superficial shave biopsy. Instead of tangentially shaving the growth, it’s “scooped out”.
- Extends into the subcutaneous fat
- Removal of some small skin cancers and melanocytic naevi.
- Leave more prominent depressed scar when compared to shave excision, but may ensure complete
removal more adequately than shave excision
- Provide valuable information about the extent of tumour invasion
Cryotherapy
- Principle: freezing damage the cells by intracellular ice formation
- Convenient in outpatient departments; highly cost effective, fast, suitable for patients fearing surgery and
lower risk of transmission of blood-borne diseases
- Downsides: no histological confirmation of diagnosis, short time pain while the procedure is being performed
- Susceptibility to damage by freezing
o Cellular components > stromal cells
o Melanocytes > keratinocytes
▪ Hypopigmentation may follow after treatment
- Freezing agents → application on a cotton bud or with a special spray gun. Tissue temperature of -50 to -60
degrees are wanted
o Liquid nitrogen: -196 degrees
o Carbon dioxide snow (dry ice): -79 degrees
Side 28 av 31
- Useful for viral warts, seborrheic keratoses, actinic cheilitis, actinic keratoses and some superficial skin
tumours like intraepidermal carcinoma and lentigo maligna
o Treatment of BCC with liquid nitrogen require significantly longer freezing time
- Lesion frozen until it turns white, 1-2 mm halo of freezing around kept as “margin”
- Two freezing cycles are usually more effective than just one
- Crust and eventually the necrotic tumour should slough off for about 2 weeks after the procedure
Curettage
- Treatment of small exophytic lesions
- The skin lesion is scraped off with a sharp blade called curette
- For certain BCC and low risk SCC
- Main advantage over for example freezing is that histological examination can still be carried out, but can’t
determine the tumour clearance as the cells on margins of the excised skin will be fragmented and
destroyed by the procedure itself
- Wound heals by secondary intention in 2-3 weeks with good cosmetic result
- Not suitable for lesions larger than 1-2 cm, rapidly growing tumours or tumours with micronodular
histological features
Electrosurgery
- Low volt, high amps → electrocautery → tissue destruction
- High volt, low amps → electrodesiccation → tissue destruction
Mohs’ micrographic surgery

- Microscopically controlled surgery to treat common types of skin cancer
- Time-consuming and expensive, but provide high tissue conservation (narrow margin) and the highest cure
rate compared with excision and curettage → used for tumours with high recurrence rate
- 97-99,8% cure rate for BCC (lower for SCC and melanoma in situ)
- First the lesion is removed with only 1-2 mm margins, mapped and rapidly frozen for histopathological
examination in horizontal sections
o 100% of the margin must be examined
- Excision, mapping, freezing and microscopic examination is done in stages until the margins are clear of
tumour cells. One stage takes around one hour and is done under local anaesthetics.
- Resulting wound: closed directly, reconstructed with a flap, covered with split-thickness skin graft or healed
by secondary intention
Radiotherapy
- Superficial radiation therapy (50-100 kV)
o Biopsy-proven skin tumours
o Adjuvant therapy after removal of high-risk skin tumours
o Usual dose: 3000 cGy given over 5-10 days
- Scars from radiotherapy worsen over time
- Increased risk of cancer in the future, so not ideal for young patients prone to skin cancer
Side 29 av 31
17) Histopathology of the skin – general principles, common terms (orthokeratosis, hyperkeratosis, acanthosis,
acantholysis, granuloma, dyskeratosis, blisters)
Hyperkeratosis – Thickening of stratum corneum, often associated with an abnormal amount of keratin. In normal skin
there’s a loose “basket weave” appearance, but in hyperkeratosis there’s usually thickening and lamination or
compaction of stratum corneum. Usually the granular layer is also thickened in hyperkeratosis. Can be caused by
vitamin A deficiency or chronic arsenic exposure. It can be treated with urea-containing creams → dissolving the
intracellular matrix of the cells of the stratum corneum → desquamation of scaly skin → softening of hyperkeratotic
lesions.
Dyskeratosis – Abnormal keratinization occurring prematurely within individual cells or groups of cells below stratum
granulosum. Histologically the abnormal keratinocytes have accumulated keratin filaments, leading to
hypereosinophilic cytoplasm and shrunken hyperchromatic nuclei.
Acanthosis – Diffuse epidermal hyperplasia (thickening of the skin). The increased thickness is localized to stratum
basale and stratum spinosum. The rete ridges are also elongated due to the thickening of the spinous layer +/-
enlargement of the rete pegs. Typical example include chronic eczematous reactions.
Parakeratosis – Mode of keratinization characterized by the retention of nuclei in the stratum corneum. Associated
with thinning of the granular layer and usually seen in diseases of increased cell turnover; inflammatory or neoplastic.
Parakeratosis is seen in the plaques of psoriasis and in dandruff.
Orthokeratosis – Hyperkeratosis without parakeratosis. No nucleus seen in the cells of the stratum corneum.
Descriptive of the normal “basket weave” appearance of stratum corneum seen in normal skin. In acral skin (palms,
soles), the stratum corneum exhibit thickening and compaction (compacted orthokeratosis).
Acantholysis – The loss of intercellular connections, such as desmosomes, leading to the loss of cohesion between
keratinocytes. This is seen in pemphigus vulgaris at the basal layer, but not in bullous pemphigoid (loss of
hemidesmosomes). In pemphigus foliaceus there’s acantholysis of keratinocytes just below the stratum granulosum.
Granuloma – Structure formed during inflammation that’s found in many diseases. Formed when the immune system
attempts to wall of substances it perceives as foreign but is unable to eliminate; bacteria, fungi, foreign objects,
keratin, suture fragments. Composed of multinucleated giant cells (macrophages) surrounded by a rim of
lymphocytes without a capsule. Can be with or without necrosis.
Blisters – A blister is a small pocket of lymph within the upper layers of the skin, typically caused by forceful rubbing
(friction), burning, freezing, chemical exposure or infection. Most blisters are filled with a clear fluid; serum or plasma,
but they can also be filled with blood or pus if they become infected.
- Vesicle = small blister
- Bulla = larger blister
Side 30 av 31
18) Pigment cells, their function, pigments in the skin
Melanocytes
- Melanin producing cells → dark pigment primarily responsible for skin colour
- Derived from neural crest
- Located in stratum basale of epidermis
- Also found in the middle layer of the eye, the inner ear, vaginal epithelium, pia mater, bones and heart
- Melanin is synthesized and contained in specialized organelles called melanosomes
- The melanosomes can be transported to nearby keratinocytes to induce pigmentation
- One melanocyte associate with a number of keratinocytes → epidermal melanin unit. One melanocyte
supplies approximately 30 keratinocytes.
o All of us, regardless of race and skin colour, have the same density of melanocytes; 1000-2000
melanocytes per square millimetre of skin
o Darker skinned people have melanocytes that produce more and larger melanosomes which are
more efficiently transferred to the keratinocytes
- Melanocytes have long processes that wind between the epidermal cells and end as discs in contact with
them though which the melanosomes are “injected” into the keratinocyte
- Once the melanosome is inside the keratinocyte, it’s engulfed into lysosomal packages and distributed
evenly throughout the cell
- HE staining: melanosomes are pale (paradoxically)
Melanogenesis
- Formed from phenylalanine
- Hydroxylation of phenylalanine by phenylalanine hydroxylase in the liver → tyrosine
- Tyrosine → dopa → dopaquinone, both reactions catalysed by tyrosinase (dopa oxidase)
o Rate-limiting step
o Melanocytes are the only cells in the epidermis with this enzyme and thus the only cells capable of
producing melanin
- Eumelanin is produced from dopaquinone
- Trichochromes (pigment in red hair) are produced when cysteine reacts with dopaquinone and incorporated
into the subsequent polymers
- Pheomelanins and eumelanins may intermesh to form mixed melanin polymers
Control of melanogenesis
- UVR is the most important factor regulating melanogenesis
- Tanning = protective mechanism of the skin against UV damage, involves two distinct reactions:
1) Immediate pigment darkening
o After exposure to longwave UV light (UVA, 320-400 nm)
o Occurs over minutes to days, depending on the UV dose and constitutive skin colour
o “false tan”, as it’s not from melanin synthesis, but oxidation of preformed melanin and redistribution
of melanin from perinuclear melanosomes to peripheral dendrites
2) Delayed tanning
o Production of new pigment 3-4 days after exposure to medium wavelength UV light (UVB, 290-320
nm)
o UVR → DNA damage → p53 activation → keratinocytes and melanocytes are stimulated to
secrete pro-opiomelanocortin
o Pro-opiomelanocortin is cleaved to alpha-MSH which binds to melanocortin 1 receptor on
melanocytes and signals for upregulation of transcription factors involved in melanogenesis
Function of melanocytes
- Protection of hypodermis from UVB damage
o Melanin is black, allowing it to absorb majority of UVB light and block it from passing through the
epidermis
- Immune function
o Phagocytic capabilities
o Presentation to T-cells
o Production and release of pro-inflammatory cytokines
o Can express MHC-II
-
Side 31 av 31

General Dermatology

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General Dermatology

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Dorthe Aslaksen Dermatology Autumn 2019

▪ 800 Langerhans cells per mm2

3) The function of the skin

Primary role: barrier.

7 main functions of the skin

5) Excretion – only minor function

Skin immune system

Dermal dendritic cell:

- Molecular components of the skin immune system: antigens, superantigens, antibodies

5) Topical therapy in dermatology

“If it’s dry, wet it and if it’s wet, dry it”

Treatment in dermatology: topical, systemic, intralesional, radiation and surgical.

Factors determining the ability of a drug to penetrate the skin:

How much should be prescribed?

o Frequency: once or twice per day, usually

Topical calcineurin inhibitors: Tacrolismus, pimecrolismus

Moisturizers → Skin disorders where barrier function is impaired

Other topical medications:

6) Systemic therapy in dermatology (i.e. antibiotics, antihistamines, retinoids, biologicals etc.)

7) Corticosteroids – topical and systemic therapy, indications, contraindications, side effects

Indications – generally for inflammatory conditions, as it has anti-inflammatory effect

Effects on the skin, when applied topically

Cutaneous side effects

Potency of topical steroids

8) Essential principles of local treatment

Categories of topical agents

9) Terminology of skin lesions, distribution of exanthemas

Key features of skin lesions

Small (<5mm) Large (>5mm)

Dermatologists use different terms to describe a lesion:

10) Distribution and patterns of skin lesions

It’s important to note:

Typical distribution of common skin diseases:

Some patterns are consistent with certain diseases:

Tzanck’s test (or Tzank smear)

12) Diagnosis – techniques – and laboratory tests of skin diseases

Special tools and techniques

Side-room and office tests (results will be available immediately)

o Readings are scored according to the reaction seen:

13) Anaphylactic shock, Hoigne syndrome

Adaptive immune system

Type III hypersensitivity

15) Phototherapy – principles

Ultraviolet radiation therapy

Narrowband UVB (311 nm) therapy

PUVA (320-400 nm) + psoralens

Photodynamic therapy (PDT)

Laser therapy (light amplification by the stimulated emission of radiation)

16) Physical therapy in dermatology

Mohs’ micrographic surgery

18) Pigment cells, their function, pigments in the skin

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