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PHOTODERRMATOSESPHOTODERRMATOSES

WITHWITH

THOMAS RUENGERTHOMAS RUENGER

MUHAMMAD KHAWAR NAZIRMUHAMMAD KHAWAR NAZIR11-10-200911-10-2009

LUPUSLUPUS ERYTHEMATOSUS ERYTHEMATOSUS

Multisystem disorder that prominently Multisystem disorder that prominently affects the skinaffects the skin

Cutaneous lesions are a source of Cutaneous lesions are a source of disability and, on many occasions, an disability and, on many occasions, an indicator of internal disease indicator of internal disease

LUPUSLUPUS ERYTHEMATOSUS ERYTHEMATOSUS

Lupus can cause disease of the skin, heart, lungs, Lupus can cause disease of the skin, heart, lungs, kidneys, joints, and nervous systemkidneys, joints, and nervous system

When only the skin is involved, the condition is When only the skin is involved, the condition is called called Discoid LupusDiscoid Lupus

When internal organs are involved, the condition is When internal organs are involved, the condition is called called systemic lupus erythematosus(SLE)systemic lupus erythematosus(SLE)

Up to 10% of persons with discoid lupus (lupus limited Up to 10% of persons with discoid lupus (lupus limited to the skin) eventually develop the systemic form of to the skin) eventually develop the systemic form of lupus (SLE).lupus (SLE).

ACUTE CUTANEOUS LUPUSACUTE CUTANEOUS LUPUS

AcuteAcute cutaneous lupus involves primarily cutaneous lupus involves primarily the epidermis and upper dermis and is the epidermis and upper dermis and is usually associated with systemic diseaseusually associated with systemic disease

▪▪    SubacuteSubacute cutaneous lupus involves cutaneous lupus involves primarily the epidermis and upper dermis primarily the epidermis and upper dermis and is and is associated with anti-Ro associated with anti-Ro autoantibodies and photosensitivityautoantibodies and photosensitivity; the ; the majority of patients majority of patients do not have significant do not have significant systemic diseasesystemic disease

CHRONIC CUTANEOUS LUPUSCHRONIC CUTANEOUS LUPUS

▪▪        DISCOID LUPUSDISCOID LUPUS involve the involve the epidermis, upper and lower epidermis, upper and lower dermis, and adnexal structuresdermis, and adnexal structures, and they can , and they can scarscar; the ; the majority of patients majority of patients do not have significant systemic diseasedo not have significant systemic disease

▪▪    Lupus Erythematosus Tumidus Lupus Erythematosus Tumidus involves the dermis but there involves the dermis but there is is no prominent adnexal involvementno prominent adnexal involvement

▪▪      Lupus Panniculitis Lupus Panniculitis involves the involves the subcutaneous tissuesubcutaneous tissue and and may result in disfiguring depressed scarsmay result in disfiguring depressed scars

LUPUS PROFUNDUS ; LUPUS PROFUNDUS ; lupus panniculitis with overlying lupus panniculitis with overlying Discoid lesionsDiscoid lesions

Relationship of ACLE to Relationship of ACLE to

CCLE and SCLECCLE and SCLE Relationship of cutaneous Relationship of cutaneous

lupus erythematosus to lupus erythematosus to systemic disease systemic disease

Ultraviolet RadiationUltraviolet Radiation

Most important environmental factorMost important environmental factor in the induction in the induction phase of SLE and especially of LE-specific skin phase of SLE and especially of LE-specific skin diseasedisease

Early studies demonstrated that Early studies demonstrated that CLE lesions could be CLE lesions could be provokedprovoked in the clinically normal skin of patients with in the clinically normal skin of patients with both SLE and CLE both SLE and CLE by repeated delivery of high by repeated delivery of high doses of UVB radiationdoses of UVB radiation to the same test site to the same test site

More recent studies argue that More recent studies argue that UVA radiation can UVA radiation can also induce CLE lesionsalso induce CLE lesions

Ultraviolet RadiationUltraviolet Radiation

UV light likely leads to UV light likely leads to self-immunity and loss of toleranceself-immunity and loss of tolerance because it because it causes apoptosis of keratinocytes, which in turn, makes previously cryptic causes apoptosis of keratinocytes, which in turn, makes previously cryptic peptides available for immunosurveillancepeptides available for immunosurveillance

UVB radiation has been shown to UVB radiation has been shown to displace autoantigens such as displace autoantigens such as Ro/SS-A and related autoantigens, La/SS-B, and calreticulin,Ro/SS-A and related autoantigens, La/SS-B, and calreticulin, from from their normal locations inside epidermal keratinocytes to the cell surfacetheir normal locations inside epidermal keratinocytes to the cell surface

Anti-SS-A/Ro Anti-SS-A/Ro Robert-antigen or soluble substance A nuclear antigenRobert-antigen or soluble substance A nuclear antigen Anti-SS-B/La Anti-SS-B/La Lane-antigen or soluble substance B nuclear antigenLane-antigen or soluble substance B nuclear antigen

UV light causes an UV light causes an exaggerated release of immune mediators in in patients with SLEpatients with SLE

Ultraviolet RadiationUltraviolet Radiation

Recent work by Meller and colleagues shows that UVB irradiation Recent work by Meller and colleagues shows that UVB irradiation induces the release of CCL27 (cutaneous T cell-attracting induces the release of CCL27 (cutaneous T cell-attracting chemokine), which upregulates the expression of chemokines that chemokine), which upregulates the expression of chemokines that activate autoreactive T cells and interferon- (IFN- ), producing activate autoreactive T cells and interferon- (IFN- ), producing dendritic cells (DCs), which likely play a central role in lupus dendritic cells (DCs), which likely play a central role in lupus pathogenesispathogenesis

UV light may additionally have an UV light may additionally have an early critical role in the inductionearly critical role in the induction phase by directly phase by directly altering cellular DNAaltering cellular DNA

UV light may UV light may affect immunoregulatory cellsaffect immunoregulatory cells, which normally help , which normally help suppress "abnormal" patterns of cutaneous inflammation.suppress "abnormal" patterns of cutaneous inflammation.

  Approach to the patient with skin lesions suspicious for CLEApproach to the patient with skin lesions suspicious for CLE

Eleven criteria have been established for the diagnosis of SLE:Eleven criteria have been established for the diagnosis of SLE:

MalarMalar (over the cheeks of the face) "butterfly" (over the cheeks of the face) "butterfly" rashrash Discoid skin rashDiscoid skin rash: patchy redness that can cause scarring : patchy redness that can cause scarring Photosensitivity: skin rash in reaction to sunlight exposurePhotosensitivity: skin rash in reaction to sunlight exposure Mucus membrane ulcersMucus membrane ulcers: ulceration of the lining of the : ulceration of the lining of the

mouth, nose or throat mouth, nose or throat ArthritisArthritis: 2 or more swollen, tender joints of the extremities : 2 or more swollen, tender joints of the extremities Pleuritis/pericarditisPleuritis/pericarditis: inflammation of the lining tissue around : inflammation of the lining tissue around

the heart or lungs, usually associated with chest pain with the heart or lungs, usually associated with chest pain with breathing breathing

Kidney abnormalitiesKidney abnormalities: abnormal amounts of urine protein or : abnormal amounts of urine protein or cellular elements cellular elements

Brain irritationBrain irritation: manifested by seizures (convulsions) and/or : manifested by seizures (convulsions) and/or psychosis psychosis

Blood count abnormalitiesBlood count abnormalities: low counts of white or red blood : low counts of white or red blood cells, or platelets cells, or platelets

Immunologic disorderImmunologic disorder: abnormal immune tests include anti-: abnormal immune tests include anti-DNA or anti-Sm (Smith) antibodies, falsely positive blood test DNA or anti-Sm (Smith) antibodies, falsely positive blood test for syphilis, anticardiolipin antibodies, lupus anticoagulant, for syphilis, anticardiolipin antibodies, lupus anticoagulant, or positive LE prep test or positive LE prep test

Antinuclear antibodyAntinuclear antibody: positive ANA antibody testing : positive ANA antibody testing

Acute Cutaneous Lupus Erythematosus Acute Cutaneous Lupus Erythematosus

Bilateral malar erythema (butterfly rash). The Bilateral malar erythema (butterfly rash). The lesions tend to be transient, lesions tend to be transient, follow sun exposurefollow sun exposure, , and and resolve without scarringresolve without scarring (but sometimes with (but sometimes with dyspigmentation)dyspigmentation)

An association with anti-dsDNA antibodies and An association with anti-dsDNA antibodies and lupus nephritis has been proposed and is plausible, lupus nephritis has been proposed and is plausible, although some patients with a malar rash have although some patients with a malar rash have neither anti-dsDNA antibodies nor lupus nephritisneither anti-dsDNA antibodies nor lupus nephritis

Patients presenting with this type of eruption must Patients presenting with this type of eruption must be be evaluated carefully for evidence of internal evaluated carefully for evidence of internal disease. disease.

Subacute Cutaneous Lupus Erythematosus Subacute Cutaneous Lupus Erythematosus

Typically photosensitiveTypically photosensitive, with lesions confined to , with lesions confined to sun-exposed skinsun-exposed skin

Non ScarringNon Scarring

Although the relationship of SCLE lesions to sun is Although the relationship of SCLE lesions to sun is striking, it is also notable that the midfacial skin is striking, it is also notable that the midfacial skin is usually spared, while the usually spared, while the sides of the face, V of sides of the face, V of the neck, and extensor aspects of the upper the neck, and extensor aspects of the upper extremitiesextremities are commonly involved are commonly involved

In some instances, lesions of SCLE have In some instances, lesions of SCLE have appeared in patients receiving appeared in patients receiving certain certain medicationsmedications, in particular hydrochlorothiazide and , in particular hydrochlorothiazide and terbinafine, but also calcium channel blockersterbinafine, but also calcium channel blockers

Regular association with the anti-Ro Regular association with the anti-Ro

autoantibodyautoantibody

Chronic Cutaneous Lupus Chronic Cutaneous Lupus

ErythematosusErythematosus

DISCOID LUPUSDISCOID LUPUS

Most common typeMost common type of cutaneous lupus of cutaneous lupus Discoid lesions are found most often on the Discoid lesions are found most often on the face, face,

scalp and ears scalp and ears

Unusual for discoid lesions to be present below the Unusual for discoid lesions to be present below the neckneck without lesions also being present above the neck without lesions also being present above the neck

Discoid lesions have the Discoid lesions have the potential for scarringpotential for scarring, and, , and,

with time, a substantial proportion of patients develop with time, a substantial proportion of patients develop disfiguring scarringdisfiguring scarring

DLEDLE

Intense inflammatory Intense inflammatory infiltrate, prominent both in infiltrate, prominent both in the superficial and deep the superficial and deep dermis and surrounding dermis and surrounding adnexal structures, is seen adnexal structures, is seen in discoid lesionsin discoid lesions

Marked hyperkeratosis with Marked hyperkeratosis with follicular plugging is also follicular plugging is also present.present.   

Immunopathology of LE–specific skin diseaseImmunopathology of LE–specific skin diseaseDirect immunofluorescenceDirect immunofluorescence examination of a Discoid examination of a Discoid Lupus Lupus

erythematosus lesional skin biopsy showing a continuous band of erythematosus lesional skin biopsy showing a continuous band of granular granular fluorescencefluorescence at the dermal-epidermal junction as a result of staining with at the dermal-epidermal junction as a result of staining with

fluorescein isothiocyanate-conjugated goat anti-immunoglobulin G.fluorescein isothiocyanate-conjugated goat anti-immunoglobulin G.

Therapy of cutaneous lupusTherapy of cutaneous lupus

Local therapyLocal therapy

Sun protection Sun protection

Topical and intralesional corticosteroidsTopical and intralesional corticosteroids

Topical calcineurin inhibitorsTopical calcineurin inhibitors

Topical retinoids Topical retinoids

Systemic antimalarial therapySystemic antimalarial therapy

HydroxychloroquineHydroxychloroquine (200 mg po qd–bid in adults; (200 mg po qd–bid in adults; up to 6.5 mg/kg ideal body weight/day)up to 6.5 mg/kg ideal body weight/day)

ChloroquineChloroquine (125–250 po qd in adults; up to 3.5– (125–250 po qd in adults; up to 3.5–4 mg/kg ideal body weight/day)4 mg/kg ideal body weight/day)

QuinacrineQuinacrine (100 mg po qd) (100 mg po qd)

CombinationCombination of hydroxychloroquine or of hydroxychloroquine or chloroquine and quinacrine (2)chloroquine and quinacrine (2)

Systemic therapy for antimalarial-resistant Systemic therapy for antimalarial-resistant cutaneous diseasecutaneous disease

RetinoidsRetinoids (e.g. acetretin, isotretinoin) (e.g. acetretin, isotretinoin)

ThalidomideThalidomide (50–100 mg po qd for clearing and, if necessary, 25–50 mg po (50–100 mg po qd for clearing and, if necessary, 25–50 mg po qd–twiceqd–twice

weekly for maintenance)weekly for maintenance)Gold Gold

DapsoneDapsone (primarily for bullous eruption of SLE) (primarily for bullous eruption of SLE)

ClofazimineClofazimine

Sulfasalazine Sulfasalazine

Immunosuppressive agentsImmunosuppressive agents (e.g., azathioprine) (e.g., azathioprine)

Systemic corticosteroids Systemic corticosteroids

Immune response modifiersImmune response modifiers (e.g., rituximab, anti-BlyS, CTLA4-Ig, anti-IL-6, (e.g., rituximab, anti-BlyS, CTLA4-Ig, anti-IL-6, anti-ILanti-IL

Adjunctive Therapy Adjunctive Therapy

Sun ProtectionSun Protection

Sun protection is a vital part of Sun protection is a vital part of therapy for many patients therapy for many patients

because the sun exacerbates because the sun exacerbates or initiates their skin lesionsor initiates their skin lesions

Sun ProtectionSun Protection sun protection is important for sun protection is important for cancer cancer

preventionprevention, particularly in hypopigmented skin , particularly in hypopigmented skin or in chronic discoid lesions, where the risk of or in chronic discoid lesions, where the risk of skin cancer development may be higherskin cancer development may be higher

Cancer prevention is also essential for patients Cancer prevention is also essential for patients who are on immunosuppressive therapy who are on immunosuppressive therapy

Sun ProtectionSun Protection It has been reported that It has been reported that sun exposure can sun exposure can

exacerbate systemic diseaseexacerbate systemic disease in patients who in patients who have SLEhave SLE

Therefore, there are a variety of reasons why Therefore, there are a variety of reasons why sun protection should be emphasized, even in sun protection should be emphasized, even in persons whose skin lesions are not induced or persons whose skin lesions are not induced or exacerbated by sun exposure. exacerbated by sun exposure.

Sun ProtectionSun Protection

Advise patients to Advise patients to avoid direct sun exposureavoid direct sun exposure

Wear tightly woven Wear tightly woven clothing clothing and broad-brimmed and broad-brimmed hatshats

Regularly use Regularly use broad-spectrum, water-resistant broad-spectrum, water-resistant sunscreenssunscreens [SPF 30 with an efficient UVA blocking [SPF 30 with an efficient UVA blocking agent such as a photostabilized form of avobenzone agent such as a photostabilized form of avobenzone (Parsol 1789), micronized titanium dioxide, micronized (Parsol 1789), micronized titanium dioxide, micronized zinc oxide, or Mexoryl SX]zinc oxide, or Mexoryl SX]

Sun ProtectionSun Protection UV-blocking filmsUV-blocking films should be applied to should be applied to home and home and

automobile windowsautomobile windows, and acrylic diffusion shields , and acrylic diffusion shields should be placed over fluorescent lightingshould be placed over fluorescent lighting

Corrective Corrective camouflage cosmeticscamouflage cosmetics such as such as Dermablend® and Covermark® offer the Dermablend® and Covermark® offer the dual benefitdual benefit of being highly effective physical of being highly effective physical sunscreenssunscreens as well as as well as aesthetically pleasing aesthetically pleasing cosmeticcosmetic masking agents masking agents

PreventionPrevention

Predicting and preventing the initial clinical Predicting and preventing the initial clinical manifestation of LEmanifestation of LE, whether it is skin disease or , whether it is skin disease or systemic, is systemic, is not feasible at this timenot feasible at this time

However, as many LE patients exhibit worsening of However, as many LE patients exhibit worsening of their skin disease activity with UV light exposure, their skin disease activity with UV light exposure, physical protection from sunlight and artificial sources physical protection from sunlight and artificial sources of UV light as well as the regular use of broad-of UV light as well as the regular use of broad-spectrum sunscreens having a SPF of 30 or greater spectrum sunscreens having a SPF of 30 or greater should be encouraged.should be encouraged.

Patient EducationPatient Education

Education on the optimal use of Education on the optimal use of sunscreens sunscreens and and protective clothing and and effective approaches to effective approaches to sun avoidancesun avoidance is important for most patients with lupus is important for most patients with lupus

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