مـصـر Egypt

3 Dr. Shoukry A. Sakr

• Consultant of Dermatology & Cosmetology. • Consultant of Andrology & Marital Relations. • Cairo university , Cairo , Egypt مـصـر Egypt

5 6

OBAGI MEDICAL CENTER KUWAIT 2006-2009 9

Dr. SHOUKRY SAKR ENCYCLOPEDIA WWW.SHOUKRYSAKRDERMAPEDIA.COM SKIN STRUCTURE

SKIN STRUCTURE SKIN STRUCTURE

Epidermis Vein

Dermis Artery

Sweat gland Hair follicle Nerve receptor Sebaceous gland 12 Hypodermis EPIDERMAL CELLS

13 EPIDERMAL CELLS

14 EPIDERMAL CELLS

15 THE DERMIS

THE DERMIS

THE DERMIS

THE DERMIS

Shaft

Sebaceous gland

Papilla Sheath

Follicle THE DERMIS

FUNCTIONS OF THE SKIN

1. The skin is the largest body organ about 6 square meters 2. Body temperature regulation i.e. thermoregulatory function 3. Prevents loss of important body fluids e.g. plasma. 4. Preventing toxic materials to enter into within the tissues. 5. Protects the body from harmful influences of factors like UVR and radiations by (melanocytes) that produce melanin which gives skin , nail and hair color. 6. Works as excretory organ : toxic substances expelled through sweat. 7. Supports and maintains the internal organs of the body. 8. Immune & infection control function. 9. Sensory organ for the pain, heat , cold , touch & pressure. 10. Manufacturer of vitamin "D" under the influence of UVR . 11. Skin is a mirror which reflects expressions as fear or joy . The internal diseases may appear to have cutaneous manifestations.

12. Skin22 texture , color and smell has a very important role in the sexual relations. PHOTODERMATOSES

23 PHOTODERMATOSES

By Dr. Shoukry Sakr

24 PHOTODERMATOSES

PHOTODERMATOSES

25 PHOTODERMATOSES

PHOTOSENSITIVITY & PHOTO-INDUCED DISORDERS [UVR (SUNLIGHT) DISORDERS ]

26 PHOTODERMATOSES

1- Effects of sunlight on normal skin 2- Acute sun damage () 3- Polymorphous light eruption (PLE) 4- Juvenile spring eruption 5- Actinic prurigo 6- 7- Actinic reticuloid 8- 9- Solar (actinic) elastosis 10- Photosensitivity : a- drug-induced phototoxic reactions 27 b- drug-induced photoallergic reactions PHOTODERMATOSES

EFFECTS OF SUNLIGHT ON NORMAL SKIN

28 PHOTODERMATOSES DEFINITION : - (or photosensitive eruption) is an eruption on light-exposed areas evolved by UVR - All human skin is sensitive to UVR , but in certain individuals or under certain conditions it becomes abnormally sensitive , being affected by low doses of UVR or wave lengths that are usually inactive 29 PHOTODERMATOSES CLASSIFICATION OF UVR : according to the wavelength 1- UVA : from 320- 400 nm 2- UVB : from 290- 320 nm 3- UVC : from 200- 290 nm

30 Sunscreens

Clothing, zinc oxide paste, shelters Blockers of UVR Window glass

Atmospheric ozone

-rays X-ray UVC UVB UVA  Visible  infrared 200 nm 290 nm 320 nm 400 nm Sunburn

Pigmentation

Skin cancer

Skin disorders & the Skin aging wavelengths which cause them Porphyria

Photoallergy

Polymorphic light reaction Photodamage & photoprotection LE

Dermatoses due to physical agents

• The solar spectrum at sea level includes wavelengths of about 290 to 3000 nm.

• The ozone in the upper atmosphere provides a barrier to wave lengths shorter than 290 nm & so the earth’s surface is shielded from the shorter wavelengths, which are inimical to most forms of life. Dermatoses due to physical agents (Cont’d)

• The sunlight which reaches ground level, therefore consists of radiation “UVR” from 290 to 400 nm, and visible radiation from 400 to 700 nm. Dermatoses due to physical agents (Cont’d)

• UVR

 UVC = < 290 nm – germicidal reaction. They don’t reach the earth’s surface.

 UVB = 290 – 320 nm (erythematogenic radiation).

 UVA = 320 – 400 nm.

• Visible light = 400 – 700 nm.

• Infrared = > 700 nm. Solar spectrum

PHOTODERMATOSES

38 PHOTODERMATOSES

39 PHOTODERMATOSES

40 PHOTODERMATOSES

41

(Cont’d)

Interaction of light with tissue

• Reflection

• Scattering

• Absorption

• Primarily UV radiation is implicated in many normal and

abnormal reactions in human skin

• Skin responses to visible light usually require a higher than

normal concentration of an endogenous chromophore (e.g. 40

µg/dL plasma-protoporphyrin) or the presence of an

exogenous dye or drug to absorb the light

Absorption

• For light to cause a chemical or biologic change,

it must be absorbed by molecules

• Without absorption of photons, no photochemical

reactions occur (Cont’d)

• Upon absorption by a molecule, the EM energy is converted to chemical energy

• Absorption of a photon promotes a molecule to a higher electronic state usually the first excited singlet state (Cont’d)

• For a given photon to have a clinical effect it must actually reach the target structure within the skin and then be absorbed by a specific chromophore within the target. (Cont’d)

• Once the photon is absorbed by the

chromophore, the source’s light energy is

transferred to the skin either to generate heat or

drive photochemical reactions 5UVR absorption spectra of molecules important to UV induced health effects DNA absorption spectrum

Photochemical reaction DNA photoproducts following UV radiation PUVA has a strong proapoptotic & a profound immunosuppressive effect but the exact mechanisms by which PUVA leads to clearance of skin lesions are still not well understood PHOTODERMATOSES

EFFECTS OF UVR : - Acute effects : 1- Erythema 2- Sunburn 3-Thickening of epidermis 4- Immediate tanning 5- Late (delayed) tanning 6- Immunologic alterations 7- Excision repair - Chronic effects (chronic actinic damage) : 1- Epidermis 2- Dermal connective tissue 3- Sebaceous glands 58 4- Melanocytes 5- Carcinogenesis

Normal response of human skin to solar radiation Acute reactions 1. Erythema “sunburn”: it is caused predominantly by UVB. After sun exposure, onset of erythema occurs within 2-6 hrs & maximal intensity occurs 15-24 hrs after exposure. Acute reac. – erythema (Cont’d)

• The minimum erythema dose “MED”: is the minimal amount of energy required to produce a uniform, clearly defined erythema response, usually at 24 hrs. UVA can cause erythema, but the dose required is very much greater. Acute reactions (Cont’d)

2. Pigmentation: there are 2 separate tanning reactions: • Immediate: produced by UVA & visible light. Occurs very soon after exposure & lasts only few hrs. It may be due to photo-oxidation of previously formed melanin. Acute reac. – pigmentation (Cont’d)

• Delayed: produced mainly by UVB, due to the formation of new melanin. It occurs few days after exposure & it protects skin against subsequent exposures. Acute reactions (Cont’d)

3. Increase thickness of epidermis

• Occurs few days after exposure and it protects against subsequent exposures. Acute reactions (Cont’d)

4. Immunologic alterations: sun exposure favors the induction of suppressor pathways:

•  OKT8 +ve &  OKT4 +ve T-cells.

• Depletion of LCs of HLA-DR molecules, eliminating their antigen presenting function. Acute reac. – immunologic alterations (Cont’d)

• Induction of non-LC APCs in epidermis  activation of T-suppressors.

• 3 weeks are required to recover from this effect. 5. Excision repair: UVR causes damage of DNA followed by excision repair, which is a mechanism mediated by endonuclease enzyme. Normal response (Cont’d) Chronic reactions “Chronic actinic damage”

• These occur especially in blue-eyed, fair- complexioned persons (Sailor’s skin or Farmer’s skin). Chronic reac. (Cont’d)

1. (premature aging): changes in appearance & function of the skin as a result of repeated sun exposure rather than to passage of time alone, e.g. coarseness, mottled pig., solar elastosis, telangiectasia, purpura & fibrotic depigmentation areas (pseudoscars). Chronic reac. (Cont’d)

• The only other environmental factor which may produce premature aging of the skin is cigarette smoking which is postulated to reduce cutaneous oxygenation.

• Treatment: 0.1 tretinoin cream. Chronic reac. (Cont’d)

2. Photocarcinogenesis (premalignancy & malignancy): e.g. solar keratosis, Bowen’s disease, basal cell carcinoma, squamous cell carcinoma, melanoma, and disseminated superficial actinic porokeratosis. PHOTODERMATOSES

CLASSIFICATION : I- Photodermatoses : A) Acute : 1- Sunburn 2- Phototoxicity (drug-induced) 3- Photoallergy : a- drug-induced b- solar urticaria 4- Idiopathic : a- polymorphous light eruption (PLE) b- actinic prurigo c- hydroa vacciniforme B) Chronic : 1- Photoaging 2- Chronic actinic dermatitis 3- Solar 4- (& actinic cheilitis) 5- Skin cancers (BCC , SCC & melanoma)

70 PHOTODERMATOSES

II) Photo-aggrevated dermatoses : A) Genetic/Metabolic : 1- Xeroderma pigmentosa 2- Bloom syndrome 3- Rothmund-Thomson syndrome 4- Hartnup dis. & aminoacidurias 5- Porphyrias 6- Cockayne syndrome 7- Pellagra B) Acquired : 1- Acne vulgaris & rosacea 2- Psoriasis 3- Atopic dermatitis & eczema 4- Darier disease 5- Disseminated superficial actinic porokeratosis 6- Lichen planus actinicus 7- Lupus erythematosus 8- Herpes simplex 9- Pemphigus foliaceous & erythematosus 9- Dermatomyositis 10- Mycosis fungoides C) Degenerative/Neoplastic : 1- Actinic keratoses 2- 3- Bowen disease 4- SCC, BCC & Melanoma 71

Classification of photodermatoses

I) Idiopathic • Polymorphous light eruption.

• Actinic prurigo.

• Hydroa vacciniforme.

• Solar urticaria.

• Chronic actinic dermatitis. Classification of photodermatoses (Cont’d)

II) Exogenous chemical

• Phototoxic.

• Photoallergic. Classification of photodermatoses (Cont’d)

III) Photoaggravated a) Genetic / metabolic • Xeroderma pigmentosum. • Bloom’s syndrome. • Cockayne’s syndrome. • Rothmund-Thomson syndrome. • Hartnup’s dis. & aminoacidurias. • Porphyrias. • Pellagra. Photodermatoses – photoaggravated (Cont’d) b) Acquired • Acne vulgaris. • LP actinicus

• Atopic dermatitis. • Acne rosacea

• Diss. superf. actinic • Darier’s dis.

porokeratosis. • H. simplex

• Pemphigus foliaceus • Psoriasis

• Reticular erythematous • LE mucinosis. Photodermatoses – photoaggravated (Cont’d) c) Degenerative & neoplastic disorders • Actinic keratoses.

• Actinic granuloma.

• Bowen’s disease.

• SCC.

• BCC.

• Melanoma. PHOTODERMATOSES

ACUTE SUN DAMAGE (SUNBURN)

77 PHOTODERMATOSES

78 PHOTODERMATOSES

79 PHOTODERMATOSES

SKIN TYPES

80 PHOTODERMATOSES

81 PHOTODERMATOSES

82 PHOTODERMATOSES

83 PHOTODERMATOSES

POLYMORPHOUS LIGHT ERUPTION (PLE)

84 Polymorphous light eruption

• It is an abnormal reaction to sunlight (usually of UVB spectrum).

• It affects young adults, usually of light- complexion, mainly from May to October every year. Polymorphous light eruption (Cont’d) Clinically

• The eruption appears 4 hrs to 6 days after sun exposure in the exposed areas, i.e. face, V area of chest, neck & arms.

• 4 types are present: papular, papulovesicular, diffuse erythematous & the plaque type (with scaly indurated plaque suggestive of DLE or lymphocytic infiltration of skin). There is no scarring or atrophy. Polymorphous light eruption (Cont’d)

Histopathology

• All types are non-specific except the plaque type: patchy lymphocytic infiltrate resembling DLE, but the patchy infiltrate is perivascular (not periappendageal) & absent basal hydropic degeneration. Polymorphous light eruption (Cont’d)

Diagnosis

• +ve phototesting with wave lengths below

320 nm (dose not rule out LE).

• -ve lupus band test is more important. Polymorphous light eruption (Cont’d)

Treatment

• Topically: steroids and sunscreens.

• Systemic: antihistaminics (Periactine®), systemic

steroids (in severe cases), anti-malarials. Polymorphous light eruption

• Most common idiopathic photodermatosis

• Prevalence: 10-20%

• Young adults (< 30 years)

• Early spring; hours to days after sun exposure

• Gets better as the summer progresses: “hardening” Polymorphous light eruption (Cont’d)

• Pruritic papules, papulovesicles, nodules, plaques

• Polymorphic in different patients; but the same morphology in the same subject

• Chronic, may become more severe, or may resolve spontaneously PMLE: Course

16 yr F/U (n=110) 32 yr F/U (n=110)

Worse 5% 5%

No change 37% 19%

Better 47% 51%

Resolved 11% 24%

T Hasan, Arch Derm 9/98; 134: 1081 PMLE: associated diseases

• 337 LE pts: 49% had symptoms consistent with PMLE

• 138 PMLE pts:

 14 pts (15%): at least 1 auto-immune disease (2 had LE)

 13 pts (14%): thyroid disease (hypothyroid, goitre, Graves’ disease) Hasan T, BJD 5/97; 136: 699; Nyberg F, BJD 2/97; 136: 217; Hasan T, Arch Derm 9/98; 134: 1081, Stockholm, Sweden PMLE

• MED: normal; may be decreased (30%)

• Action spectrum  UVA (50%)

 NB-UVB (50%)

 NB-UVB + UVA (80%)

 Visible • Photopatch negative PMLE

Provocative phototest

• Single exposure (3-5 x MED)

• Repeated exposures (UVA, 100 J/cm2; UVB, 1.5 x MED. Daily for 3 days)

• Exposure to sunlight PMLE: photoprovocation

• 68 pts

• Photoprovocation with BB-UVB, NB-UVB & BB-UVA. 3 consecutive days

• Positive reaction  UVA: 50%

 NB-UVB: 50%

 Both (probability): 81%

 BB-UVB: 18% PMLE: pathophysiology

• 22 PMLE pts; 23 controls

• Exposure to solar simulated radiation, followed by sensitization to DNCB on irradiated site  assessment of CHS

• Erythema: pts = controls

• 1 MED suppressed CHS by 78% in controls, by 44% in pts (p < 0.01) PMLE: pathophysiology

• PMLE pts are more resistant to UV-induced

immunosuppression

• “Hardening”, UV-desensitization: induction of

photoimmunosuppression in these pts PMLE: treatment

• Sun avoidance, sunscreen

• UVB (NB & BB)

• PUVA

• Hydroxychloroquine

• Oral corticosteroid (short course)

• Azathioprine PHOTODERMATOSES

100 PHOTODERMATOSES

101 PHOTODERMATOSES

JUVENILE SPRING ERUPTION

102 Juvenile spring eruption

• It is seen in early spring mainly in children

as grouped papules and vesicles on the

light-exposed helix of the ear. Juvenile spring eruption

• Predominantly in young boys

• 13/18: Fam hx of JSE or PMLE

• Pruritic papules or vesicles within hours of sun exposure

• Ears

• No scarring PHOTODERMATOSES

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106 PHOTODERMATOSES

ACTINIC PRURIGO (HUTCHINSON SUMMER PRURIGO)

107 Actinic prurigo (Hutchinson’s summer prurigo)

• Onset: in contrast to PLE, in childhood. There is prurigo-like papules, small vesicles & pitted scars present throughout the year but worst in summer involving exposed & covered areas. There is frequent personal or family history of atopy. Actinic prurigo

• Familial (75%) American Indian

• Female : Male = 3 : 1

• Photosensitivity usually to UVA

• Face, nose, ears

• Cheilitis, conjunctivitis, photophobia

• Tx: thalidomide, PUVA, NB-UVB Actinic prurigo: histology

• Epidermal hyperplasia, spongiosis

• Vacuolar alteration of basal cells

• Thickening of basement membrane

• Dense lymphoid infiltrate in dermis

• Lymphoid follicles (lips) Actinic prurigo & HLA

• UK (Caucasian) & Mexico DR4 (subtype DRB1*0407)

• N. Am. Indian A24, Cw4

• Colombia Cw4, Cw3, B40

• Canadian Inuit (Eskimo) DR4 (subtype DRB1*14) PHOTODERMATOSES

112 PHOTODERMATOSES

113 PHOTODERMATOSES

HYDROA VACCINIFORME

114 Hydroa vacciniforme

• Onset: early childhood.

• There is deep-seated umbilicated vesicle on exposed areas.

• Healing occurs with large varioliform scars. Hydroa vacciniforme

• Scotland 1973 – 1997

• 17 pts: 9 M, 8 F

• Age of onset: 7.9 yrs (M: 8.7 yrs; F: 6.7 yrs)

• Bimodal onset: 1-7 yrs, and 12-16 yrs EBV & hydroa vacciniforme

• 6 pts with HV

• Epstein-Barr virus in skin

 6/6: EBV-RNA

 5/6: EBV-DNA

• Latent EBV is associated with HV EBV-associated HV-like eruption

• Mexico, Japan, Korea, Taiwan

• Disfiguring edema (face), erythema, vesicles, ulceration, scars on sun-exposed & sun- protected areas

• Fever, wasting, hepatosplenomegaly, vasculitis, panniculitis

• May progress to lymphoma or leukemia EBV-associated HV-like eruption

• Many associated with latent EBV-infection

• Children & adults

• Action spectrum: UVA

• Two patterns  Recurrent facial necrotic papules / vesicles

 Nodules & facial edema PHOTODERMATOSES

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121 PHOTODERMATOSES

CHRONIC ACTINIC DERMATITIS

122 Chronic actinic dermatitis “CAD”

• It seems that photosensitive eczema “PE”, persistent light reactivity “PLR” & chronic photosensitivity dermatitis “CAD” has been proposed to consider this syndrome as a whole.

• The condition affects mainly elderly men over 50 yrs of age. The diagnosis of CAD depends on:

• Persistent eczematous eruption of sun-exposed skin with possible extension into non-exposed areas.

3 • Photosensitivity to UVB (

• Histologically, evidence of chronic eczema, with or without lymphoma-like changes. CAD (Cont’d)

Pathogenesis

• Transition from photoallergy to persistent light reactivity.

• Alteration in some normal skin component during the photoallergic reaction becomes antigenic on its own. CAD – pathogenesis (Cont’d)

• If CAD supervenes, UVB irradiation may trigger the delayed-type hypersensitivity response at any site by formation of an antigenic photoproduct from the endogenous carrier protein alone or in the absence of exogenous irritating agents. CAD (Cont’d) Treatment

• Avoid UV & allergen exposure.

• PUVA.

• Systemic treatments with azathioprine, danazol or cyclosporine, have been tried. Chronic actinic dermatitis

• Persistent light reactivity

• Photosensitive eczema

• Actinic reticuloid

• Photosensitivity dermatitis & actinic reticuloid syndrome Chronic actinic dermatitis – diagnotic criteria

• Chronic photodermatitis

• Low phototest results to UVA &/or to UVB &/or to visible light

• Histology: dermal lymphohistiocytic infiltrate   Epidermal spongiosis

  Atypical mononuclear cells CAD: patient profile

• All patients:

 65%: decreased MED-A & MED-B

 27%: decreased MED-A only

• 35 NY pts: 63% had skin types V & VI (clinic: 10- 37% V / VI) CAD: Natural history

(n = 178 pts; 24 yr follow-up) • Prevalence: 1 per 6000 • Poor prognosis  Severe abnormal UVB photosens

 2 or more positive patch tests • Probability of resolution  10% (1 in 10) in 5 yrs

 20% (1 in 5) in 10 yrs

 50% (1 in 2) in 15 yrs CAD: Disease association

• HIV

• Atopic dermatitis CAD – pathophysiology

• Contact allergy to plants (compositae oleoresins – 75%

in one study), fragrances, chromates, rubber

• Outdoor workers / gardeners in British patients; not in

US or Japanese patients (Lim HW, JAAD 1998; 38: 108) CAD – pathophysiology

• Action spectrum of CAD pts with decreased MED-

B: similar to that of sunburn reaction

• Kinetics of expression of adhesion molecules is

similar to that in delayed hypersensitivity reaction CAD – pathophysiology

• CAD: ? Type IV response to unidentified antigen,

probably DNA or related molecule, in the context of

airborne contact dermatitis-enhanced immune

reactivity or photoimmuno-suppression CAD – treatment

• Sunscreen, sun protection

• PUVA & oral corticosteroid

• Azathioprine

• Mycophenolate mofetil (CellCept) + PUVA + po steroid

• Mycophenolate mofetil

• Cyclosporine

• Topical tacrolimus

• Hydroxychloroquine

• Hydroxyurea CAD – treatment

• Broad spectrum sunscreen

• Benzophenones

• Avobenzone (= Parsol 1789)

• Mexoryl

• Tinosorb

• Titanium dioxide

• Zinc oxide PHOTODERMATOSES

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139 PHOTODERMATOSES

ACTINIC RETICULOID

140 Actinic reticuloid

• The condition occurs almost exclusively in elderly men.

• There is lichenified plaques first in exposed areas, but later the eruption gradually spreads to cover most of the skin surface  erythroderma & generalized LN enlargement. Actinic reticuloid (Cont’d)

• There is  thickening (deep furrows) and of the exposed areas.

• Itching is severe.

• The action spectrum is usually UVA, but shorter UVR (290-320 nm) may produce abnormalities. Actinic reticuloid (Cont’d) Histopathology

• There is band-like infiltrate of lymphoid & histiocytes in upper dermis & may extend into the lower dermis or invade into epidermis  aggregates resembling Pantrier microabscesses. Actinic reticuloid – histopathology (Cont’d)

• In spite of its resemblance to MF or Sezary’s syndrome, it is benign & reversible. Also, T-cells in skin lesions & circulation are of the suppressor (OKT-8) type whereas in the CTCL it is of helper (OKT-4) type. There are several reports of lymphoma developing in patients with actinic reticuloid. Actinic reticuloid (Cont’d) Treatment

• Systemic steroids.

• Azathioprine.

• PUVA.

• Sunscreens are usually ineffective. PHOTODERMATOSES

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147 PHOTODERMATOSES

SOLAR URTICARIA

148 Solar urticaria “SU”

• It is characterized by immediate urticarial

response to sunshine occurring in sun-exposed

skin.

• Systemic symptoms may occur if there is

sufficient mast cell release. SU (Cont’d) Pathogenesis • A chromophore (precursor) present in the skin or in the circulation, or both may absorb radiation  photoallergen formation. IgE- mediated hypersensitivity to this photo-allergen then develops with mast cell activation. SU (Cont’d) Classification of SU Mechanism AS • Type I • Allergic • UVB • Type II • Unknown • UVA • Type III • Unknown • Visible light • Type IV • Allergic • Visible light • Type V • Unknown • UVA, UVB, visible light • Type VI • Protoporphyrin • Visible light AS = action spectrum. Type VI is considered erythropoietic protoporphyria. SU (Cont’d) Treatment • Avoidance and sunscreens.

• Terfenadine, astemazole alone or with cimetadine.

• PUVA: it may cause depletion of mast cell contents. Solar urticaria

• Visible & UVA: most common action spectrum

• Hardening in 28% of pts

• Atopy in 21 – 48% of pts Solar urticaria

• 87 pts (1975 – 2000)

• Mean age: 41 yrs. 70% female

• F/u period: 4 yrs (3 mo to 26 yrs)

• Prevalence: 3.1 per 100,000

• Action spectrum: long UVA & short visible radiation Solar urticaria (Cont’d)

• Coexistence of:

 PMLE: 20/87 (23%)

 CAD: 3/87 (3%) • Probability of resolution of those with SU alone:

 5 yrs: 15%

 10 yrs: 24%

 15 yrs: 46% Solar urticaria – Action spectrum

• Visible

• UVA

• UVB Solar urticaria – Therapy

• Antihistamine

• NB-UVB, BB-UVB, UVA, fluorescent lamp

• PUVA

• Cyclosporine

• Plasmapheresis

• IVIG UVA hardening for solar urticaria

• Start with 70% MUD, increase by 40 to 20%

• Treat only exposed areas

• Start with daily treatment, then increase to twice a daily (6 h apart), 5 d/wk, 18-26 tx

• Max dose: 15.6 J/cm2

• Daily sun exposure, 15-30 min UVA rush hardening for solar urticaria

• 3 pts with solar urticaria (act. Spec: UVA + vis, UVA, UVA + UVB)

• Start with 50% MWD in one quadrant

• Expose the other quadrants at 1 hour interval

• Half body irradiation, 1 hour interval, increase by 30% UVA rush hardening for solar urticaria (Cont’d)

• Second day: start with last dose, less 30%

• Expose as before

• Final dose: 10 J/cm2

• Provoke with 50 J/cm2

• Maintenance: 10 J/cm2, 1 – 2 x/wk PHOTODERMATOSES

161 PHOTODERMATOSES

162 PHOTODERMATOSES

SOLAR (ACTINIC) ELASTOSIS

163 Solar “actinic” elastosis

• It occurs after prolonged exposure to sun’s rays

especially in fair-skinned persons.

• Small yellowish papules & plaques develop on face &

backs of the hands. The skin shows deep furrows &

wrinkles & subject to development of actinic keratoses

& carcinomata. Solar elastosis (Cont’d)

Cutis rhomboidalis nuchae

• The skin on the back of the neck becomes

thickened and tanned with exaggerated

normal skin markings. Solar elastosis (Cont’d)

Histopathology

• Hx & E: in upper dermis, there is basophilic

degeneration of the collagen separated from the

atrophic epidermis by a narrow band of normal

collagen. Solar elastosis – histopathology (Cont’d)

• By elastic tissue stain: there are aggregates of

thick, interwoven bands of elastotic material

which is newly formed by fibroblasts which are

no longer capable of producing normal elastic

fibers or collagen. Nodular elastosis with cysts & comedones (Favre- Racouchot syndrome)

• Some patients with pronounced solar elastosis of the facial skin show especially lateral to the eyes, multiple comedones as well as yellowish nodules & contain a central comedo.

• A variant of nodular elastosis with cysts & comedones is the actinic comedonal plaque. Nodular elastosis (Cont’d)

• It is found as a solitary plaque on sun-

damaged skin of either the arms or the

face.

• The plaque shows small nodules & dilated

follicles. Nodular elastosis (Cont’d)

• Histopathology: pronounced solar elastosis, dilated pilosebaceous openings & large, round cysts that are lined by a flattened epidermis & represent greatly extended hair follicles. Nodular elastosis (Cont’d)

Erythema AB Igne

• Prolonged exposure to moderate heat emanating from fireplaces, radiators or heating pads causes a persistent reticular erythema with or without pigmentation.

• The shins and buttocks are the most common sites. PHOTODERMATOSES

172 PHOTODERMATOSES

173 PHOTODERMATOSES

PHOTOSENSITIVITY

174 PHOTODERMATOSES

- It occurs when an individual has been exposed to a photosensitizing drug or chemical - Types : A) Drug-induced phototoxicity : which can occur in all individuals & essentially an exaggerated sun burn response . It is a non-immunologic reaction e.g. phyto- photo dermatitis (poison ivy) from a plant origin. B) Drug-induced photoallergy : it is an immunological reaction , in which the eruption is a rash 175 Photosensitivity

• A number of substances known as

“photosensitizers” may induce an abnormal

reaction in skin exposed to sunlight.

• These photosensitizers come in contact with the

skin through external or internal routes. Photosensitivity (Cont’d)

Phototoxic reactions • It is a non-immunologic reaction that can be elicited in the majority of individuals 2-6 hrs after exposure to the photosensitizers, if given in sufficient dose & in association with exposure to light of proper wave length (usually 280-450 nm). Photosensitivity – phototoxic reac. (Cont’d)

• Phototoxic drug reactions: manifested as

severe sunburn without itching, e.g. with

sulfonamides , demecolocycline, doxycycline &

psoralens. Photosensitivity – phototoxic reac. (Cont’d)

• Phototoxic contact dermatitis: as with coal tar derivatives & psoralens as oil of bergamot which are present in some perfumes  Berloque or perfume dermatitis which is manifested as streaking or drop- shaped lesions on sides of neck. PHOTODERMATOSES

BERLOQUE DERMATITIS

180 PHOTODERMATOSES

181 PHOTODERMATOSES

182 Photosensitivity (Cont’d)

Photoallergic reactions • It is a cell-mediated, delayed immunologic response that can be elicited only in small no. of individuals who have been sensitized by previous exposure to photosensitizer drugs & at the same time to light as in allergic contact dermatitis. Photosensitivity – photoallergic reac. (Cont’d)

• The role of light consists in altering either the hapten itself or the avidity with which the hapten combines with the carrier protein to form a complete photoantigen.

• A photoallergic drug eruption causes a photocontact dermatitis in all light-exposed areas. Like any allergic contact dermatitis, it causes itching. Photosensitivity – photoallergic reac. (Cont’d)

Histopathology

• Histopathology of allergic contact dermatitis shows

epidermal spongiosis & micro-vesiculation, a

perivascular lymphoid cell infiltrate & exocytosis. Photoallergic reac. – histopathology (Cont’d)

• Photoallergic drug reactions: e.g. chloro-thiazides,

tolbutamide (oral antidiabetic), phenothiazines

(chlorpromazines).

• Photoallergic contact dermatitis: e.g. sulfa-

thiazides & antihistamines. Phototoxicity Photoallergy

Incidence High Low

Rxn w/ 1st exp Yes No

Incubation No Yes

Onset Min to days 24 – 48 hr

Drug conc High Low

Clinical Blisters hyperpig Erythema edema

Histology Necrot kerat Spong derm PHOTODERMATOSES

188 Phototoxins in the environment

• Furocoumarins (fragrances, psoralens, lime, celery, carrots, figs, parsley, parsnips)

• Tar

• Dyes (eosin, methylene blue, rose bengal, flavinoids) Systemic phototoxic agents

• Cardiac (amiodarone, nifedipine, quinidine)

• Diuretics (furosemide, thiazides)

• Hypoglycemics (sulfonylureas)

• Nonsteroidals (benoxaprofen, ketoprofen, naproxen, piroxicam)

• PDT agent (HPD, hypericin)

• Psychotropics (chlorpromazine, desipramine, imipramine) Systemic phototoxic agents

• Antibacterials (quinolones, tetracyclines, sulfonamide)

• Antihistamine (diphenhyramine)

• Antimalarials (chloroquine, quinine)

• Antimitotics (fluorouracil, vinblastine)

• Antipsoriatic (psoralens) Photoallergens

Sunscreens

• Benzophenone 3 (oxybenzone)

• Benzophenone 4 (sulisobenzone)

• Padimate O (octyl dimethyl PABA)

• Padimate A (amyl dimethyl PABA)

• Para-aminobenzoic acid (PABA) Photoallergens

Sunscreens

• Cinnamates (most commonly used agent)

• Avobenzone (Parsol 1789)

• Anthranilate (cyclohexanol)

• Homosalate Photoallergic contact dermatitis

• 2715 pts; 1983 – 1998

• 62 pts (2.3%) with PACD

• In the 62 pts: UV filters (65%), drugs (20%), musk ambrette (14%), antiseptic trichloro-carbanilide (1%) Photoallergic contact dermatitis (Cont’d)

UV filters

• Benzophenone 3: most common cause of PACD. Commonly used

• Others: rarely used

• Octyl methoxycinnamate: only 2 positive reaction in 12 yrs

• PACD to UV filters: uncommon Photoallergens

Fragrances

• Must ambrette*

• 6-methylcoumarin*

• Sandalwood oil Photoallergens

Antimicrobials

• Halogenated salicylanilides*

• Hexachlorophene (pHisHex)

• Chlorhexidine (Hibiciens)

• Bithionol*

• Fentichlor* Photoallergens

Others

• Chlorpromazine (Thorazine)*

• Promethazine (Phenergan)* PHOTODERMATOSES

DRUG-INDUCED PHTOTOXICITY

199 PHOTODERMATOSES

200 PHOTODERMATOSES

201 PHOTODERMATOSES PHYTO-PHOTODERMATITIS

202 PHOTODERMATOSES

203 PHOTODERMATOSES PHOTO-ONYCHOLYSIS

204 PHOTODERMATOSES

205 PHOTODERMATOSES

DRUG-INDUCED PHOTOALLERGY

206 PHOTODERMATOSES

207 PHOTODERMATOSES

208 What’s New in

Photodermatoses • Cutaneous porphyrias :

• -erythropoietic protoporphyria (EPP)

• -congenital erythropoietic porphyria (CEA) &

• -X-linked dominant protoporphyria (XLDPP). (Cont’d)

• EPP :

• New treatments are emerging for this disabling

photosensitivity disorder.

• Congenital erythropoietic porphyria, a rare & severe

photo-mutilating disorder, has now been studied by a

comprehensive study in Europe. (Cont’d)

• The range of severity for CEP from mild to severe has been recorded for the first time.

• Additionally, the full extent of disease complications has now been identified & recorded.

• X-linked dominant protoporphyria, a newly described porphyria characterized by similar biochemical changes to EPP. (Cont’d)

• The mechanism for protoporphyrin accumulation is

different in XLDPP compared to EPP.

• The significantly higher risk of protoporphyrin-

induced liver disease in XLDPP gives this condition a

poorer prognosis than EPP. (Cont’d)

• De novo cholesterol synthesis is fundamental to human health as demonstrated by the severe multi-organ disorder that occurs in the congenital metabolic condition in which cholesterol synthesis is defective.

• An unexpected discovery in this condition (the Smith- Lemli-Opitz syndrome or SLOS) is severe photosensitivity in more than 50% of patients. (Cont’d)

• The wide range of disability characterized by children with SLOS & the poor prognosis mean that dermatologists are seldom asked to see these patients.

• The photosensitivity is to UVA: dermatologists can therefore give appropriate advice for photo-protection including the use of a suitable sunscreen. (Cont’d)

• Pellagra, a condition taught at medical school but rarely encountered in medical practice in developed countries, remains an enigma.

• It is certainly not “new” but a fresh look at this condition has revealed some important insights. (Cont’d)

• Pellagra was the first photosensitivity disorder to be described in the medical literature more than 200 years ago.

• It remains a problem in poor countries whose population is over-reliant on corn for nutritional survival.

• Until now, pellagra has eluded precise photobiological characterization due to its rarity in developed countries. (Cont’d)

• It is likely to be a UVA-mediated photosensitivity disorder.

• However, the pathogenesis of the severe photosensitivity pellagra has yet to be determined.

• Corn remains a staple component of diet in most developing countries; if relied upon to the exclusion of a more varied diet, pellagra is a potential consequence. (Cont’d)

• Population growth and climate change make it

likely that pellagra will continue to be a health

problem in the poorest underdeveloped countries

in the coming decades. PHOTODERMATOSES

PHOTOAGEING

220

“Photoageing – what dermatologists should

know”? What’s new in photoageing

• Clinical picture and morphology

• Pathogenic role of ultraviolet light Clinical picture of photoageing

Superimposition of chronic cumulative ultraviolet (UV) damage on intrinsic aging process Intrinsic ageing

• Benign hyperproliferations

• Dry thin appearance

• Fine wrinkling (Cont’d) Photoageing

• Epidermal damage o Pigment changes o Premalignant & malignant skin changes • Dermal damage o Deep wrinkling o Loss of resilience o Increased fragility, & o Reduced wound healing Pigment changes Premalignant changes Premalignant changes Deep wrinkling – loss of resilience Clinical picture – effect of skin type

Phototype I – II • Telangiectasia Phototype III – IV • Fine wrinkling • Leathery quality of skin • Atrophy • Deep wrinkling • Actinic keratoses • Diffuse hyperpigmentation Photoageing: morphology

Epidermis

• Variability in epidermal thickness, atypia of keratinocytes & melanocytes, loss of langerhans cells

Dermis

• Solar elastosis: increased synthesis of elastinin, however elastin does not assemble into functional fibers

• Loss/damage of collagen Pathogenic role of ultraviolet light

• UV induces matrix metalloproteinases (MMPs), which degrade collagen

(Quan et al, 2009)

• Role of mitochondria: defective powerhouse model (Krutmann, 2009)

• Disruption of telomere loop as a common final pathway in ageing &

photoageing (Gilchrest, 2009)

Advances in Photoageing (Cont’d)

• Photoageing is the superposition of chronic ultraviolet (UV)-induced damage on intrinsic ageing & accounts for most age-associated changes in skin appearance.

• It is mediated by membrane & nuclear signaling through ROS generation that inhibits phosphatases whose function is to maintain receptors in their inactive state. (Cont’d)

• Receptor activation induces intracellular signaling culminating in activation of the nuclear transcription complex AP-1 that interferes with collagens I & III transcription & synthesis.

• Increased AP-1 activity also increases the levels & activity of several enzymes that degrade extracellular matrix components, like MMP-1 (collagenase), MMP-3 (stromelysin-1) & MMP=9 (92- kd gelatinase). (Cont’d)

• UV also activates the nuclear B transcription factor that induces the expression of pro-inflammatory cytokines like interleukin (IL)-1 & IL-6, vascular endothelial growth factor (VEGF), & tumor necrosis factor (TNF-) & aggravates the degradation of dermal matrix by increasing the levels of MMP-1 & MMP-9. (Cont’d)

• Matrix degradation is further exacerbated by MMP-8 (collagenase) of neutrophil origin as a result of neutrophil infiltration into UV-irritated skin.

• Although there is a concomitant upregulation of tissue inhibitors of metalloproteinases (TIMPs) that limit matrix degradation, TIMPs presumably are not completely effective in blocking cumulative damage to dermal collagen. (Cont’d)

• A recently identified transcription factor family of proteins, FoxO, regulates cellular metabolism, stress resistance & lifespan extension in mammals, induces the transcription of procollagen I & decreases the transcription of MMP-1 & -2.

• UV decreases FoxO mRNA level further compromising collagen I synthesis & increasing MMP-1 & -2 synthesis. (Cont’d)

• UV-induced collagen degradation is generally incomplete, leading to accumulation of partially degraded collagen fragments in the dermis, thus reducing the structural integrity of the skin.

• In addition, the large collagen degradation products inhibit new collagen synthesis, & thus collagen degradation itself negatively regulates new collagen synthesis. (Cont’d)

• UV radiation, both directly & through generation of ROS induces the transcription of tropoelastin, a component of the mature elastic fibers.

• Fibulins 2 & 5 & fibrillin-1, components of the microfibrillar fraction of the dermal elastic fiber are also increased in photodamaged skin. (Cont’d)

• Furthermore, increased elastase levels are present in photodamaged skin as a result of elastase synthesis & secretion by neutrophils that are attached to the area by inflammatory mediators.

• Thus, excessive unbalanced synthesis of elastic fiber components that undergo partial degradation results in the formation of amorphous elastotic material in the dermis. (Cont’d)

• Another mechanism involved in photoageing is mitochondrial damage.

• Mitochondria are cellular organelles that produce energy (adenosine, triphosphate) by consuming oxygen.

• Although equipped with antioxidant defense systems, continuous generation of ROS damages mitochondrial DNA (mtDNA). (Cont’d)

• To date, machinery to remove bulky DNA lesions has

not been identified in mitochondria, although they

display capacity for base excision repair relevant to

repair of oxidative damage. (Cont’d)

• Still, mtDNA mutation frequency is approximately 50-

fold higher than that of nuclear NDA, & photodamaged

skin has higher mtDNA mutation frequency than sun-

protected skin, displaying large DNA deletion &

resulting in decreased mitochondrial function. (Cont’d)

• This leads to further accumulation of ROS & compromises the

cellular ability to generate energy.

• Also, a correlation was noted between decreased

mitochondrial function & increased MMP-1 levels without

concomitant increase of MMP-1 specific TIMP, exacerbating

collagen degradation & aggravating skin photoageing. (Cont’d)

• Proteins, are directly affected by oxidative damage, & photodamaged skin shows accumulation of oxidized, damaged proteins in the upper portions of the dermis.

• In vitro studies suggest that UVA is a major contributor & the accumulation of such proteins further inhibits proteasomal function & the ability of the cell to successfully degrade these damaged proteins. (Cont’d)

• In sun-exposed skin the basement membrane becomes thicker & multilayered in part as a result of damage through MMP activation.

• Basement membrane damage affects molecular transfer between the epidermis & the dermis & compromises the health of the epidermis. (Cont’d) • Telomeres are tandem repeats of a short sequence TTAGGG & cap the terminal portion of chromosomes, preventing their fusion.

• Because the terminal portion of the DNA cannot be replicated, the final 100-200 bases of the telomeres are lost with each cell division, & when telomeres reach a critically short length the cell will no longer divide & will enter a state of replicative senescence. (Cont’d)

• Telomeres normally exist in a loop configuration,

with the loop held in place by the final 150-200

bases on the 3’ strand that forms a single-

stranded overhang. (Cont’d)

• It has been postulated that when the loop is disrupted as telomeres become critically short, for example after repeated cell divisions, or when telomeres are damaged as a result of UV irradiation or other agents, the overhang becomes exposed & through interaction with the Werner protein activates the tumor suppressor protein p53 & other DNA damage response proteins to induce proliferative senescence or apoptosis, depending on the cell type. (Cont’d)

• Throughout life & particularly in sun-exposed skin,

DNA damage accumulates in cutaneous cells

interfering with cellular metabolism & function.

• One system that is particularly susceptible to DNA

damage is that of growth hormone & insulin growth

factor. (Cont’d)

• It is thought that shifting the energy utilization of the cell

from growth & proliferation of damaged cells to

preserving the somatic functions of the cells has evolved

as a way of ensuring the well-being of the organisms as a

whole & as a cancer preventing mechanism. (Cont’d)

• Indeed, papillary dermal fibroblasts display age

associated modification in secreted MMPs, cytokines

& proliferative capacity consistent with the above

concept & they lose their ability to support epidermal

growth & differentiation. (Cont’d)

• Non-enzymatic modifications of tissue proteins by reducing sugars, the so-called Maillard reaction results in the formation of advanced glycation end-products (AGE-products).

• This is a prominent feature of ageing & photoageing.

• AGE-products by binding their cognate receptors interfere with dermal fibroblast function & induce fibroblast senescence. (Cont’d)

• Possible intervention modalities for ageing & photoageing

include Resveratol, a phenolic substance present in red wine

thought to activate protein deacetylases that help maintain

telomere structural integrity, induce transcriptional silencing

of genes that promote ageing, modulate mitochondrial

function & activate FoxO. (Cont’d)

• A recent interest in Rhamnose-rich oligo- & polysaccharides

as a possible treatment for cellular skin ageing has been

invoked, as by binding membrane receptors, these

polysaccharides inhibit AGE-product harmful effects on

fibroblasts. (Cont’d)

• In conclusion, photoageing is a complex process

determined by the genetic makeup of the individual as

well as by environmental factors.

• As dermatologists, we are committed to find ways to

assist in healthy skin ageing & in preserving cutaneous

structure & function. (Cont’d)

• To achieve these goals we must identify the mechanisms

responsible for photoaging at the molecular level & strive to

reduce their impact on the individual through the development

of sophisticated diagnostic tools & intervention strategies

aimed at prevention, regeneration & remediation to postpone

cutaneous decline. PHOTODERMATOSES

Photoageing Lesions : 1- 2- Solar lentigens 3- Colloid melium 4- Solar elastosis 5- Idiopathic guttate hypomelanosis 6- Cutis rhomboidalis nuchae 7- Favre-Raccouchot syndrome 8- of Civatte

264 PHOTODERMATOSES

FRECKLES

265 PHOTODERMATOSES

266 PHOTODERMATOSES

267 PHOTODERMATOSES

SOLAR LENIGINES

268 PHOTODERMATOSES

269 PHOTODERMATOSES

270 PHOTODERMATOSES

COLLOID MILIUM

271 PHOTODERMATOSES

272 PHOTODERMATOSES

273 PHOTODERMATOSES

SOLAR ELASTOSIS

274 PHOTODERMATOSES

275 PHOTODERMATOSES

276 PHOTODERMATOSES

IDIOPATHIC GUTTATE HYPOMELANOSIS

277 PHOTODERMATOSES

278 PHOTODERMATOSES

279 PHOTODERMATOSES

CUTIS RHOMBOIDALIS NUCHAE

280 PHOTODERMATOSES

281 PHOTODERMATOSES

282 PHOTODERMATOSES

FAVRE-RACCOUCHOT SYNDROME

283 PHOTODERMATOSES

284 PHOTODERMATOSES

285 PHOTODERMATOSES

POIKILODERMA OF CIVATTE

286 PHOTODERMATOSES

287 PHOTODERMATOSES

288 PHOTODERMATOSES

PHOTO-AGGREVATED DERMATOSES

289 PHOTODERMATOSES

A) Genetic/Metabolic : 1- Xeroderma pigmentosa 2- Bloom syndrome 3- Rothmund-Thomson syndrome 4- Hartnup dis. & aminoacidurias 5- Porphyrias 6- Cockayne syndrome 7- Pellagra B) Acquired : 1- Acne vulgaris & rosacea 2- Psoriasis 3- Atopic dermatitis & eczema 4- Darier disease 5- Disseminated superficial actinic porokeratosis 6- Lichen planus actinicus 7- Lupus erythematosus 8- Herpes simplex 9- Pemphigus foliaceous & erythematosus 9- Dermatomyositis 10- Mycosis fungoides C) Degenerative/Neoplastic : 1- Actinic keratoses 2- Actinic granuloma 3- Bowen disease 4- SCC, BCC & Melanoma

290 PHOTODERMATOSES

PHOTOPROTECTION ANTI-AGING RULES

291 Photoprotection

• A moderately cloudy day or an umbrella offers only limited photoprotection.

• White sand reflects most UVR.

• Sun-avoidance is the best method of photo-protection, i.e. reducing outdoor exposure from 10:00 am till 3:00 pm. Photoprotection (Cont’d)

• Hats, long sleeves, tightly dry shirts are the most practical means of photoprotection.

• Avoidance of prolonged exposure to fluorescent lamps is important.

• Window glass blocks virtually all UVB and at least 50% of UVA energy. Sunscreens

• Drugs that protect the structure &

functions of the skin against actinic

damage. Sunscreens (Cont’d) I) Topical sunscreens: applied ½ hr before sun exposure.

• Physical, e.g. Titanium dioxide, Talc, Zn oxide, …etc., which act as reflectors & scattering agents, form an opaque barrier to all sunlight but they are cosmetically unacceptable, can discolor clothes & may promote miliaria & folliculitis. They are of limited protection when a person sunbaths for few hrs. Topical sunscreens (Cont’d)

• Chemical: are usually non-opaque, colorless & contain an absorbing chemical, e.g.  Para-aminobenzoic a. (PABA) & PABA esters: it penetrates the st. corneum where it can remain attached to proteins through hydrogen bonding. It can give protection after bathing, swimming or perspiring. It is absorbed predominantly within the UVB range. Topical sunscreens – chemical (Cont’d)

 Benzophenones, e.g. oxybenzone. They absorb UVB & shorter wavelengths of UVA.

 Cinnamates: they absorb mostly UVB & some UVA. They don’t bind to st. corneum & so, more easily removed.

 Dibenzoylmethanes: more effective UVA screen, but a poor UVB absorber. Topical sunscreens (Cont’d)

Efficacy of sunscreen

• Depends on the vehicle, pH, stability, SPF, the type of the skin (color & thickness), environment, sweating, substantivity (the sunscreen remains effective after prolonged sweating or swimming). Topical sunscreens (Cont’d)

The sun protection factor “SPF”

MED of sunscreen-treated skin = MED of non-protected skin Topical sunscreens (Cont’d)

• Sunscreens with an SPF of 15 or more filter more than 92% of UVR responsible for erythema & make sunburn unlikely.

• Type 1 & 2 skin need SPF of 15 or more, while type 3 needs only SPF 4, e.g. Photoplex®, Shade®, Nivea sun®. you have to order the no. of SPF you need. Topical sunscreens (Cont’d)

The new superpotent sunscreens

• With SPF-30 or more. However, as it blocks Vit. D

synthesis, so in elderly, more liable to bony

fractures, 3 glasses of milk/day are

recommended. Topical sunscreens (Cont’d)

UVA sunscreens • UVA is not erythemogenic but it can cause

erythema with very great dose. It is

important in photosensitivity reactions. Topical sunscreens (Cont’d)

MPD (minimal phototoxic dose)

= Minimal amount of UVA required to

produce erythema in photosensitized skin

(psoralen is usually used). Topical sunscreens (Cont’d)

PPF “phototoxic protection factor”

MED of sunscreen-treated skin = MED of non-protected skin

• Topical psoralen in sunscreen tan acclerators due to stimulation of melanogenesis. Topical sunscreens (Cont’d)

Sun protection is advised to:

• Fair-skin (skin types 1 & 2).

• Sun-sensitivity disorders.

• Personal or family history of skin cancer.

• Outdoor occupations. Sunscreens (Cont’d)

II) Systemic photoprotection

• e.g. psoralens, beta-carotenes and

antimalarials. Antimalarials

Mechanisms of action

• Light filtration: they bind to DNA which prevents DNA & RNA polymerase reactions & prevents DNA heat inactivation & so provides a protective effect from damage caused by UVR. This nucleoprotein binding also leads to inhibition of LE cell formation, ANAs formation & rheumatoid factor production. Antimalarials – mechanism of action (Cont’d)

• Immunosuppression: they inhibit the

formation of immune complexes & so

effective in SLE & related autoimmune

diseases. They interfere with IL-1

secretion by monocytes. Antimalarials – mechanism of action (Cont’d)

• Anti-inflammatory action: by stabilizing lysosomal membranes, inhibition of hydrolytic enzymes, interferences with prostaglandin synthesis, blocking of chemotaxis & antagonism of histamine responses. Antimalarials – mechanism of action (Cont’d)

• Porphyria cutanea tarda: chloroquine form

molecular complexes with porphyrin with

subsequent increase in urinary excretion

of porphyrins.

Light (400 nm)

Hydrogen Excited Damaged Porphyrin &/or lipid porphyrin membranes peroxides Porphyrias (Cont’d)

• If an infant’s diapers have a

reddish discoloration, think of

Erythropoietic porphyria. Porphyria cutanea tarda (Cont’d)

What’s pseudo-PCT

and

What’s pseudo-pseudo-PCT?

Phenyl ketonuria “PKU”

• Deficiency of phenylalanine hydroxylase enzyme

leading to the accumulation of phenylalanine &

its metabolites as phenyl pyruvic acid in serum

& urine. Alkaptonuria

• If an infant’s diaper have a

black discoloration, think of

Alkaptonuria.

Sunscreens & prevention of skin cancer

• How does skin type affect the risk for skin cancer?

• What are the other risk factors for skin cancer?

• Do hereditary factors affect skin cancer risk? Sunscreens & prevention of skin cancer (Cont’d)

• What age or sex factors are important in skin cancer risk?

• What should physicians teach patients about skin cancer prevention?

• What warning signs of possible skin cancer should be looked for in the self-skin exam? Sunscreens & prevention of skin cancer (Cont’d)

• How is ultraviolet light classified?

• List the 13 basic facts regarding sun protection.

• What type of clothing is considered sun- protective? Sunscreens & prevention of skin cancer (Cont’d) • What are sunscreens?

• Compare the advantages & disadvantages of the physical & chemical sunscreens.

• How is an SPF determined?

• How much sunscreen should be applied? How often should it be reapplied? Sunscreens & prevention of skin cancer (Cont’d)

• Can sunscreens be safely used in children?

• Are tanning pills safe to use?

• What about “tan-in-a-bottle” lotions?

• What is proper sunburn treatment? Controversy 1

• Does the use of sunscreens enhance the

development of skin cancers? Sunscreens & melanoma

• Systematic reviewed of all studies from 1966 to 2003

• No evidence to support the relationship between

sunscreen use and an increased risk of melanoma Sunscreens & NMSC

• A 4.5 yr + 8 yr f/u study of 1621 residents of Nambour,

Queensland, randomly assigned to daily SPF16 broad

spectrum sunscreen group, vs. control.

• SCC incidence rates: significantly decreased by 38%

• BCC incidence rates: decreased by 25%, but not significantly Sunbeds & skin cancer

• Systematic review of literature till 3/06 (casecontrol, cohort, or cross-sectional studies)

• “Ever-use” of sunbeds: positively associated with melanoma, but no consistent doseresponse relationships

• First exposure before 35 years of age: significantly increase the risk

• Increased risk of SCC

• No association with BCC Controversy 2

• Does the use of sunscreens result in vitamin D

insufficiency? Photoprotection & serum level of Vit D

50 pts w/ photosensitive LE, 25-OH-D (48 SPT I-III; 2 SPT IV; adequate level: 75 nmol/L):

• 64%: < 80 nmol/L

• 4%: < 25 nmol/L

201 pts w/ EPP, 25-OH-D:

• 63%: < 50 nmol/L

• 17%: < 25 nmol/L Sunscreen use & serum level of Vit D

• Reviewed published evidence

• Conclusion: While sunscreens can significantly reduce the

production of Vit D under very strictly controlled conditions,

their normal usage does not generally results in Vit D

insufficiency Sun exposure & Vit D

• Studies from Santiago (Chile), Honolulu, Kashmir

(India), East Asia: > 50% of individuals living in areas

with sunny climates had inadequate serum vitamin D

levels Skin types & Vit.D levels

• 25-OH-D levels in the US:

o Whites: 80 nmol/L

o Mexican Americans: 60 nmol/L

o African Americans: 50 nmol/L (Cont’d)

• Indv > 60 yo: 67% of whites, 88% of African

Americans, had < 80 nmol/L

• UK Asians: children: 20-34% < 25 nmol/L; adults: 50-

60% <12.5 nmol/L Skin types & Vit D levels Controversy 3

• Is oxybenzone in sunscreens a hormonal

disruptor? Estrogenic effects of sunscreens

• In vitro and in rat model (oral administration): Some UV filters had estrogenic effects

• However: o Doses used were unrealistically high

o Estrogenic potency: 1 million-fold less than estradiol

• Human study: no change in hormonal levels Controversy 4

• Does the presence of retinyl palmitate in

sunscreens and other topical products promote

photocarcinogensis? Retinyl palmitate (RA)

• RA is a storage form of retinol (vitamin A)

• It is present in many sunscreens and cosmetics

• In vitro: RA + UVA can generate reactive oxygen

species → may be photomutagenic (Cont’d) However:

• In mice, topical RA + solar simulated radiation: did not enhance photocarcinogenesis

• Topical retinoids have been in used for over 40 years; no evidence of photocarinogenicity

• Oral retinoids are used for chemoprevention of skin cancers No clinical data to suggest that RA is photo-carcinogenic Review of Sunscreens

Marianne N O’Donoghue, MD Associate Professor of Dermatology Rush University Medical Center Chicago, Illinois

Why the need for better sunscreens?

• Photoaging

• Actinic keratoses

• Basal cell carcinoma

• Squamous cell carcinoma

• Melanomas

Solar spectrum Why protect against UVA?

• UVA has been documented to cause a decreased immunoservalence against skin cancer

• UVA causes more dyspigmentation

• UVA stimulates vimentin (dermal damage)

• UVA causes oxidative DNA damage leading to mutations

Why protect against UVB?

• UVB is both an initiator & promoter of basal cell and squamous cell carcinoma

• Repeated UVB contribute to malignant melanoma

• Basal cell carcinomas are usually caused before age 20

• Actinic keratoses & squamous cell carcinomas reflect current exposure What weapons do we have?

• Physical sunscreens

• Chemical sunscreens

• Special clothing

• Avoid the outdoors between 10-2

• Seek out the shade Physical sunscreens

• Zinc oxide & titanium dioxide

• The older preparations were effective for noses, shoulders, and under the eyes

• These were traditionally used by life-guards, children and some skiers

• They scatter and absorb UVR Micronized formulations of zinc oxide & titanium dioxide

• Titanium dioxide absorbs UVB & UVA from 290-340 nm, which includes UVA II

• Zinc oxide absorbs UVB & UVA from 290-380 nm, which includes UVA II & I

• Zinc oxide therefore has better coverage

• Both ingredients are hypoallergenic & non-toxic Inorganic sunscreens Pros & Cons of these sunblocks

• Patients can have a ghost-like appearance when these are applied

• These should be the first choice for patients with sunscreen allergy

• They have been incorporated into many combination sunscreens to increase the SPF Chemical sunscreens

• UVB chemical sunscreens (290-310 nm)

• Padimate O

• Cinnamates

• Salicylates

• Octocrylene

• Phenylbenzimidazole sulfonic acid Chemical sunscreens UVB absorbers Chemical Absorption (nm) P-aminobenzoic acid (PABA) 250 – 320 (288) Octyldimethyl PABA 290 – 315 (310 Glyceryl PABA 264 – 315 (295) Ethyl dihydroxy PABA 280 – 330 (309) Octyl methoxycinnamate 290 – 320 (308) Octocrylene 250 – 380 (303) Ethoxy methoxycinnamate 280 – 320 (310) Octyl salicylate 280 – 320 (300) Homomenthyl salicylate 295 – 315 (306) Padimate O

• Only PABA still available

• Great substantivity – binds to horny layer

• Doesn’t cross-react with p-phenylamine diamine as much as the parent compound

• Goes into cosmetic preparations easily

• Used now in hair cosmetics rather than skin Cinnamates

• Octyl methoxycinnamate & Cinoxate cover wave lengths from 270 – 328 nm

• Major ingredients in color cosmetics which have an SPF factor

• Most common UVB ingredient in medical sunblocks

• Very rarely cause contact dermatitis Salicylates

• Homosalicylate was the original standard for measuring SPF (4.5)

• The salicylates function to strengthen the SPF in most medical sunblocks

• Octyl salicylate & triethanolamine can cause photocontact dermatitis

• Homosalicylate causes no photocontact dermatitis Octocrylene

• This ingredient has been the favorite of non-comedogenic sunscreens (290 – 360 nm)

• It is easily formulated into gel sunscreens

• This was the best UVB ingredient to stabilize Avobenzone (Parsol 1789)

• It is rarely allergenic & causes no photoallergy Phenylbenzimidazole sulfonic acid

• One of the major UVB protectors in the Olay brand of products

• No reports of allergy or photoallergy

• Protects from 290 – 320 nm UVA chemical sunscreens

• Benzophenones

• Avobenzone (Parsol 1789)

• Tetraphalydine dicamphor sulfonic acid (Mexoral SX) Chemical sunscreens UVA absorbers Chemical Absorption (nm)

Oxybenzone 270 – 350 (290, 325)

Dioxybenzone 200 – 390 (284, 327)

Sulixobenzone 250 – 380 (286, 324)

Menthyl anthranilate 200 – 380 (336)

Butyl methoxydibenzoyl-methane (Parsol 1789) 200 – 400 (356) Benzophenones

• Oxybenzone (270 – 350 nm)

• Dioxybenzone (206 – 380 nm)

• Sulisobenzone (250 – 380 nm)

• These were the major ingredients for UVA protection until the 1990’s Advantages & disadvantages

• These ingredients go into cosmetics very easily. They form a nice product

• These have the highest incidence of contact & photocontact dermatitis of all of the sunscreens

• The photocontact dermatitis is brought out by intense sun or heat

• They are not as effective as Parsol 1789 Avobenzone (Parsol 1789)

• This ingredient is only for UVA protection (310 – 400 nm)

• It is cosmetically elegant

• The most effective UVA ingredient available besides the physical sunscreens

• It is stable when combined with Octocrylene, but only for a limited time

• It may protect against Benzophenone allergy What is the defect of Avobenzone?

• As it is exposed to higher levels of UV energy, it becomes unstable

• Octocrylene protected this ingredient better than the cinnamates

• The newer broad spectrum sunblocks must protect this – the most important ingredient An example of Avobenzone photoinstability in a sunscreen formulation Tetraphalydine dicamphor sulfonic acid (Mexoral SX)

• Broad spectrum sunscreen from L’Oreal in Paris & Canada

• Not available in USA until July 2006

• Good reputation for protecting LE patients & others very sensitive to UVR

• Since 1993 this product has been available in Europe & Canada to protect avobenzone Types of Mexoral

• Mexoryl SX is water soluble

• Mexoryl LX is an oil soluble UVA filter

• The filter protects avobenzone What comprises HelioplexTM technology?

Photostable UVA

• Contains avobenzone – provides broad UVA protection

• Contains diethylhexyl 2,6-naphthalate (DEHN) – an avobenzone stabilizer

• Contains benzophenone (oxybenzone, sulisobenzone, or dioxybenzone) – stabilizes avobenzone & adds UVA protection

• Added SPF drivers for UVB protection Helioplex technology (Cont’d)

• DEHN accepts the excess energy absorbed by avobenzone & transfers it to oxybenzone, which fluoresces it as red light. This has been observed with ultraviolet photography & imaging. Thus, the UV light is being converted now to harmless red light without sacrificing the ability of the avobenzone to absorb photons Neutrogena data on file

• Using solar stimulator exposures of product

samples to evaluate photostability, it was

determined that the Helioplex product is more

stable than the Mexoryl containing product. Mechanism of action of HelioplexTM Mechanism of action of HelioplexTM Waterproof importance

• The label “water-resistant” or “stable” means the

product can resist 40 minutes of lap swim

• The label “water-proof” or “very stable” means the

product can resist 80 minutes of lap swim

• Patients should reapply sunscreen regularly SPF & broad spectrum

• SPF refers only to UVB protection

• A minimum of 15 is suggested

• For patients with Fitzpatrick’s skin types I & II, 30 or higher is suggested

• The patient needs to apply 2 mg/cm2 & usually isn’t that generous

• Broad spectrum refers to the UVA coverage Cosmetic sunscreens

• Clinique

• Lancome

• Chanel

• Estee Lauder

• Generic Conclusions

• Use sunscreen daily

• Reapply it often

• Wear protective clothing

• Avoid high sunshine hours

• Take or consume Vitamin D References

• Hanson KM, Simon JD: Epidermal trans-urocanic acid & the UVA-induced photoaging of the skin. Proc Natl Acad Sci 95: 10576-10578, Sept 1998.

• Galis C, Giraf S, Mavon A, et al: Assessment of skin photoprotective capacities of an organo-mineral broad- spectrum sunblock on two ex vivo skin models Photodermatology, Photoimmunology & Photomedicine 19 (5): 242-53, Oct 2003. References (Cont’d)

• Duncan KO: Epidermal neoplasms & adnexal tumors in Kerdal FA, Jimenez-Acosta F, Dermatology – Just the Facts, McGraw-Hill, New York, 2003, 252-57.

• Berne B, Ros AL: Seven year experience of photopatch testing with sunscreen allergens in Sweden. Contact Dermatitis 38: 61-4, 1998.

Anti aging rules

7Antiaging Rules

I) Exercise II) Diet III) Life style IV) Weight V) Regular check-ups VI) Balance your hormones VII) Improve your skin, hair and nails

Generously apply a water resistant sunscreen with at least SPF 15 that provide UVB/UVA protection to all sun exposed areas and re apply every two hours and after activities as toweling, swimming,… Wear protective clothing such as long sleeved shirts, brimmed hats, sun glasses,…

Seek shade specially at the time from 10:00 am to 4:00 pm. Sun exposure is the most preventable risk factors of skin cancers , including melanoma, You canProtect have children fun in the (ABCS) sun by being sun smart.

Use extra caution near water, snow and sands that reflect the damaging sun rays that increase the chance of sun burn..

Get vitamin D Safely and don’t seek the sun. Avoid tanning beds as it can cause wrinkles and skin cancer , use sunscreen with it.

Check your birthday suite on your birthday, if you notice any skin abnormality, immediately consult your dermatologist. It is estimated that we get about 80% of our total life sun exposure ,in the first 18 years of life hence sun protection is very important in childhood to prevent Skin cancer later in life.

Advances in Photomedicine: Topical & Oral Strategies for Non-sunscreen Photoprotection

Advances in photomedicine (Cont’d)

• Sun avoidance,

• Sun protective clothing

• Conventional sunscreens,

• Other non- sunscreen protective strategies .

Advances in photomedicine (Cont’d)

These include:

• Anti-oxidant ingredients for topical application

• Topical DNA repair enzymes,

• Botanical extracts for topical & systemic use, &

• Oral supplements claimed to provide protection against sun exposure.

Advances in photomedicine (Cont’d)

• Topical DNA repair enzymes were first introduced over a

decade ago as a potential therapy for UV-induced damage,

especially for those individuals genetically deficient in repair

enzymes (xeroderma pigmentosum). Advances in photomedicine (Cont’d)

• Topical application of repair enzymes, although effective

only post-UV exposure, may be an important new weapon

in the fight against actinic cancers.

Photodamage EBM3

The intake of tomato paste for 10 wk protect against UV-induced erythema.

Stahl et al., J. Nutr. 2001

SkinDecreases Cancer the thickness of the dermal fat Antioxidant Anti-inflammatory Sunscreen (topical mainly)

Hsu JAAD 2005 EBM3

Regular tea consumption may be associated with a reduced risk of NMSCs. Rees et al., JAAD 2007

Advances in photomedicine (Cont’d)

• Oral supplements have been under study as a possible protective

approach against sun exposure.

• For example, 10 weeks of ingesting 2 ½ T of tomata paste was

shown to increase the MED in volunteers. Advances in photomedicine (Cont’d)

• These foods have included grape seeds

proanthocyanidins, green tea catechins, certain fish

oils, antioxidant vitamins & Polypodium leucotomos (a

fern extract). Photodamage EBM3

The intake of tomato paste for 10 wk protect against UV-induced erythema.

Stahl et al., J. Nutr. 2001 Photodamage

Tomato peel is an important option for increasing lycopene.

Reboul et al., J. Nutr. 2005

Sunscreens Final Monograph FDA- August 2007 AAD response November 2007 Okinawans

Longest average lifespan in the world 80% fewer breast and prostate cancer 50% fewer ovarian and colon cancer 80% fewer heart attacks Skin wrinkles Foods & skin wrinkling Full-fat milk Sweet milk dessert Ice-cream Butter Sugar Skin wrinkles EBM3

Higher intakes of vitamin C & linoleic acid & lower intakes of fats and carbohydrates are associated with better skin-aging appearance.

Cosgrove et al ., Am J Clin Nutr 2007 Skin wrinkles Diet predictors of skin wrinkles EBM2

Meat ; 2.2 Sugar; 1.2 Dairy; 0.9 Cereal; -1 Vegetables; -1.9 Fish; -2.3 Legumes; -3.4 Oils; Purba-5.6 et al., -6 J Amer-5 College-4 Nut 2001-3 -2 -1 0 1 2 3 Skin wrinkles Reversal of wrinkles by diet ! Skin wrinkles EBM3

Fibroblasts treated with a soy extract showed increasing collagen & HA synthesis. Topical application of an isoflavone significantly enhanced the number of dermal papillae after 2 weeks.

Sudel et al., Photochemistry & Photobiology, 2005 Skin wrinkles EBM1

Soy extractThis , fishdiet protein is result PLS, in whiteimproving tea extract, the appearance grape seed extract, tomato extract, Vitamins C,& conditionE , Zinc and of chamomile skin. extract for 6 months

Skovgaard et al ., Eur J Clin Nut 2006 Photodamage Phytochemicals الكرفس الشاى األخضر Green tea فول الصويا Soybean

العنب األحمر Red grape

الحرشف البرى Milk thistle

البقدونس Parsley, celery, lettuce الكركم Curcuma longa الزنجبيل Ginger الفواكه و الخضرواتvegetables & الملونة Pigmented fruits الطما طم Tomato الخس ,. Adhami et al Photochemistry & Photobiology 2008

Sunscreens & prevention of skin cancer

• How does skin type affect the risk for skin cancer?

• What are the other risk factors for skin cancer?

• Do hereditary factors affect skin cancer risk? Sunscreens & prevention of skin cancer (Cont’d)

• What age or sex factors are important in skin cancer risk?

• What should physicians teach patients about skin cancer prevention?

• What warning signs of possible skin cancer should be looked for in the self-skin exam? Sunscreens & prevention of skin cancer (Cont’d)

• How is ultraviolet light classified?

• List the 13 basic facts regarding sun protection.

• What type of clothing is considered sun- protective? Sunscreens & prevention of skin cancer (Cont’d)

• What are sunscreens?

• Compare the advantages & disadvantages of the physical & chemical sunscreens.

• How is an SPF determined?

• How much sunscreen should be applied? How often should it be reapplied? Sunscreens & prevention of skin cancer (Cont’d)

• Can sunscreens be safely used in children?

• Are tanning pills safe to use?

• What about “tan-in-a-bottle” lotions?

• What is proper sunburn treatment? Advances in photoprotection (Cont’d)

• The solar terrestrial radiation spectrum is arbitrarily divided

into three ranges: short wave (UVC, 200-280 nm) mostly

excluded by the ozone layer; mid-wave (UVB, 280-315 nm), &

long-wave (UVA, 315-400 nm).

• Wavelengths shorter than 290 nm are absorbed by

stratospheric ozone & do not reach the surface of the Earth. (Cont’d)

• The most biologically effective solar radiation is UVB that is the main cause of sunburn & skin cancer.

• However, patients with photodermatoses react both to UVB, UVA &/or visible light & comprehensive guidance in photoprotection for fair skin & photosensitive patients is important. (Cont’d)

• In recent decades considerable evidence has emerged concerning the value of reducing exposure to ultraviolet radiation (UVR).

• Ninety per cent of skin cancers are related to UVR exposure.

• Most of the changes considered to constitute skin ageing are really attributable to photoageing. (Cont’d)

• In intermittently sunny countries, the incidence of photosensitivity is of the order of 20% of the population.

• The three pillars of an effective photoprotection strategy include behavior, clothing & the effective use of topical sunscreens. (Cont’d)

• Firstly, fair-skinned people & photosensitive patients

should avoid direct sun exposure.

• This may be achieved by protection from different

glass types in cars or houses, by seeking shade &

considering the time of day & time of year when

outside. (Cont’d)

• UV excluding clothing is the next approach.

• Several studies reported efficacy of high-protection

sunscreens in the prevention of photodamage &

photodermatoses.

• The sunscreen should effectively protect from both UVB (SPF

30-50) & UVA. (Cont’d)

• Lack of compliance is common despite repeated instructions of patients in sunscreen application.

• Variable attitudes in patients which may be disease specific explain why patients with cutaneous lupus comply well with sun protection, whereas those with polymorphous light eruption (PLE) comply very poorly. (Cont’d)

• Photosensitive patients if possible cover up with clothing, as most fabrics provide good protection from UVR.

• Desensitization phototherapy with UVA, UVB & PUVA has been shown to significantly increase the patient’s tolerance of sunlight regardless of which photodermatosis is being treated. Sunscreens

• The SPF is defined as the dose of solar radiation needed to induce just perceptible erythema (minimal erythema dose, MED) on skin treated with 2 mg/cm2 sunscreen divided by the MED on untreated skin. Thus, the SPF primarily describes protection from UVB, as it reflects protection from the erythema action spectrum. (Cont’d)

• No standard method exists to measure the UVA protection of sunscreens but protection from persistent pigment darkening is commonly used. Topical sunscreens are broadly divided into organic (chemical) and inorganic (physical) agents. (Cont’d)

• So called organic sunscreens contain mineral

particles (titanium dioxide and zinc oxide) which

reflect and scatter UVB, UVA and visible radiation

by forming an opaque barrier of inert metal

particles. (Cont’d)

• Microfine particles are mainly UVB sun blocks, whereas cosmetic grade particles protect against longer wavelengths including visible light.

• No adverse events in humans have been described from nanoparticles of TiO2. (Cont’d)

• The main problem with inorganic sunscreens in their

current form is that they are often cosmetically

unacceptable by the white appearance that follows their

physical properties, and the amount applied by users of

inorganic sunscreen is often less compared with organic

sunscreen. (Cont’d)

• Micronized forms of physical sunscreens are less

visible on the skin but the reduction in particle

size results in less UVA protection.

• However, the absorption of UVB is higher. (Cont’d)

• Organic sunscreens act by absorbing ultraviolet radiation

and re-emitting chemical energy as heat or light. Several

chemical filters exist that shield against UVB, UVA or both.

• Since the filters are specific for given wavelengths, they

are often combined in sunscreens to obtain broad-

spectrum protection. (Cont’d)

• Adverse events from the use of organic sunscreens

occur more often in patients suffering from

photodermatoses and include allergic and irritant contact

dermatitis, phototoxic and photoallergic reactions,

contact urticaria, and in rare cases anaphylactic

reactions. (Cont’d)

• The effect of sunscreens as photoprotection in particular

photodermatoses is described in subsequent chapters.

• Several studies have reported efficacy of broad-spectrum,

high-protection sunscreens in the prevention of

polymorphic light eruption. (Cont’d)

• Lack of compliance among patients suffering from

photodermatoses has been reported and may account for

variable effect.

• The median application thickness was found only to be 0.5 4

mg/cm2, which will reduce a declared SPF 50+ into an effective

SPF of as low as 2-3. (Cont’d)

• This is important since the use of a broad-spectrum sunscreen SPF 50+ in a correct amount has been shown to be highly effective protecting very UV- sensitive patients suffering from idiopathic solar urticaria when tested in a standardized setting. (Cont’d)

• The patients in this study reported only slight protection from previous use of sunscreens while they after the study reported much better protection.

• This stresses the need for thorough instructions and insight of the patients in sunscreen application, amount used and effect from correct use. (Cont’d)

• Especially the ears, temples, posterior and lateral

neck tend to be completely overlooked when applying

sunscreen.

• The instructing physician needs to be aware of this. (Cont’d)

• The sunscreen should effectively protect from both

UVB (SPF 30-60) and UVA and preferably the

sunscreen should contain a combination of inorganic

and organic sunscreen filters since they have been

shown to act synergistically. (Cont’d)

• Dihydroxyacetone (DHA) (fake tan) provides a modest protection from UVB, UVA and visible light if applied to the whole body surface, is usually evenly applied, visible and lasts several days.

• The SPF achievable with DHA is of the order of 2-3.

• This in combination with other photoprotective strategies is useful for some patients. Adequate clothing

• Clothing is one of the most important tools for sun protection

of fair skinned people. The protection afforded by clothing

fabrics is measured as the Ultraviolet Protection Factor (UPF)

based on the transmittance of ultraviolet radiation through a

given fabric. (Cont’d)

• The European Standard for Sun-protective Clothing

states that fabrics labeled as UV-protective must give an

UPF larger than 40 as well as an average UVA

transmission lower than 5% to provide sufficient

protection from sun exposure. (Cont’d)

• The UPF is commonly determined in vitro by a

radiometer or a spectrophotometer.

• The UPF is calculated as the ratio of the UV intensity

before and after passing through a fabric sample

weighted against the erythema action spectrum. (Cont’d)

• The UPF thus mainly describes protection from sunburn

caused by UVB Several factors affect transmission of UVR

through clothing fabric.

• Thicker, tight-woven, dry and dark-colored clothing

provide good protection and polyester, denim and wool

are superior to cotton, linen and rayon. (Cont’d)

• This may not be comfortable in warm weather and

instead addition of UV absorbers can increase the

UPF of light-weight clothes. (Cont’d)

• Whether clothing with an UPF 40+ is necessary is controversial since light weight clothing achieves higher protection than the UPF 10.

• Assessing the design and fabric weave in most instances is common sense.

• If a fabric transmits visible light it may not be UV protective. Photoadaptation

• In the clinic, phototherapy with UVA, UVB and PUVA is frequently used to prevent photodermatoses.

• This treatment induces pigmentation and thickening of the stratum corneum, which provide the skin a certain degree of natural photoprotection . (Cont’d)

• However, other mechanisms through immuno-modulation are believed also to account for the effect of phototherapy.

• The use of a narrow-band UVB (TL-01) or UVA phototherapy course in springtime has been shown to effectively increase the UV tolerance of patients with photodermatoses . (Cont’d)

• Narrow-band UVB (TL-01) phototherapy or

photochemotherapy with PUVA improve symptoms

significantly and is equally effective.

• Photoadaptation is only suited to the photosensitive

patient as very low dose regimens are used. Vitamin D & Photoprotection

• Numerous studies have shown that sunscreen use alone does not render people vitamin D deficient.

• However, studies have shown that those who are strictly avoiding sun are indeed often vitamin D deficient and need supplementation. (Cont’d)

• The best way of managing this is to check vitamin D. levels and give a supplement if required.

• There is huge variation because of dietary variability, cultural attitudes to the sun and behavioral differences. هذا ماأعلم وهللا أعلى وأعلم والعلم كله عند هللا

480 Thank you Dr. SHOUKRY SAKR

481