shri ganasaya namaha. an update on psoriasis by dr. mahesh mathur, md,dvd,dcp (uk) md,dvd,dcp (uk)

SHRI GANASAYA NAMAHASHRI GANASAYA NAMAHA

AN UPDATE ONAN UPDATE ONPSORIASISPSORIASIS

BYBY

DR. MAHESH MATHUR, DR. MAHESH MATHUR, MD,DVD,DCP (UK)MD,DVD,DCP (UK)

DEFINITIONDEFINITION

COMMON, CHRONICCOMMON, CHRONIC GENETICALLY DETERMINEDGENETICALLY DETERMINED INFLAMATORY & PROLIFERATIVEINFLAMATORY & PROLIFERATIVE CHARACTERISED BY CHARACTERISED BY

- - Well defined,Well defined,

- Dull red- Dull red - Silvery white scaling- Silvery white scaling - involving extensor aspect of body- involving extensor aspect of body - great variability in extent of - great variability in extent of

disease, morphology of lesions & disease, morphology of lesions & duration of disease. duration of disease.

EPIDEMIOLOGYEPIDEMIOLOGY

INCIDANCE & PREVELANCEINCIDANCE & PREVELANCE

1.5 TO 4.8%1.5 TO 4.8% AGE OF ONSET - can occur at any age- AGE OF ONSET - can occur at any age-

5 TO 9 YEARS IN FEMALE- TYPE -I5 TO 9 YEARS IN FEMALE- TYPE -I

15 TO 19 YEARS IN MALE- TYPE-115 TO 19 YEARS IN MALE- TYPE-1

30 TO 40 YEARS- TYPE II30 TO 40 YEARS- TYPE II

RACEAL DIFFERENCERACEAL DIFFERENCE

AETIOLOGY & PATHOGENISISAETIOLOGY & PATHOGENISIS

INHERITED – INHERITED – NO SINGLE PATTERN, NO SINGLE PATTERN, MULTIFACTORIAL MULTIFACTORIAL

MHC CLASS 1 –CW6- 80% ASSOCATION MHC CLASS 1 –CW6- 80% ASSOCATION WITH TYPE I PSORIAIS WITH TYPE I PSORIAIS

FAMILIAL - FAMILIAL - TWIN SUDY – MONOZYGOT PAIR 73%TWIN SUDY – MONOZYGOT PAIR 73%

DIZYGOTC PAIR 20 %DIZYGOTC PAIR 20 %

50% SIBLINGS 50% SIBLINGS IN IN PROBAND PROBAND

WHEN BOTH WHEN BOTH

PARANTS ARE AFFECTED PARANTS ARE AFFECTED

PROVOCATION & EXACERBATIONPROVOCATION & EXACERBATION

TRAUMATRAUMA INFECTIONINFECTION ENDOCRIN FACTO- Pregnancy, MenopauseENDOCRIN FACTO- Pregnancy, Menopause SUN LIGHTSUN LIGHT METABOLICMETABOLIC DRUGS - DRUGS - lithium, beta blocker, antimalarials,systamic lithium, beta blocker, antimalarials,systamic

steroidssteroids PSYCOGENICPSYCOGENIC ALCOHOLALCOHOL AIDSAIDS

PATHOGENESISPATHOGENESIS

T CELL MEDIATEDT CELL MEDIATED KERATINCYTE PROLIFERATIONKERATINCYTE PROLIFERATION HLA CW 6HLA CW 6

IS IT AN IS IT AN IMMUNOLOGICAL IMMUNOLOGICAL

DISEASE ?DISEASE ?

YESYES…..….. CD4+ T CELLS IN DERMISCD4+ T CELLS IN DERMIS CD8+ CELLS INFILTRATING IN EPIDERMIS – CD8+ CELLS INFILTRATING IN EPIDERMIS –

MHC I RESTRICTEDMHC I RESTRICTED MACROPHAGES & NEUTROPHILS MACROPHAGES & NEUTROPHILS

INFILTRATIONINFILTRATION IL1,IL6,IL8,TGF alfa,LTC4, C5aIL1,IL6,IL8,TGF alfa,LTC4, C5a IMMUNO THERAPY BY IMMUNO THERAPY BY METHOTRAXTEMETHOTRAXTE

T CELL MEDIATED T CELL MEDIATED

PATHOLOGY & PATHOGENESISPATHOLOGY & PATHOGENESIS KERATINOCYTE PROLIFERATIVE KERATINOCYTE PROLIFERATIVE

ACTIVITY-ACTIVITY- VASODILATATION OF DERMAL VASODILATATION OF DERMAL

VASSELSVASSELS * * EIGHT FOLD SHORTENING OF EPIDERMAL CELL EIGHT FOLD SHORTENING OF EPIDERMAL CELL

CYCLE CYCLE

* * 36 ~311 h IN NORMAL36 ~311 h IN NORMAL

*TWOFOLD INCRESE IN PROLIFERATIVE CELL *TWOFOLD INCRESE IN PROLIFERATIVE CELL POPULATIONPOPULATION

*100% OF GERMINATIVE CELLS ENTER IN GROWTH *100% OF GERMINATIVE CELLS ENTER IN GROWTH FRACTION- 35,000 CELLS/ SQ.mm~1218 CELLS/SQ.mmFRACTION- 35,000 CELLS/ SQ.mm~1218 CELLS/SQ.mm

PATHOGENESISPATHOGENESIS

CLINICAL PRESENTATIONCLINICAL PRESENTATION

CLINCAL VARIENTCLINCAL VARIENT PLAQUE PSORIASISPLAQUE PSORIASIS GUTATE PSORIASISGUTATE PSORIASIS FLEXURALFLEXURAL NAPKIN PSORIASISNAPKIN PSORIASIS UNSTABLE -UNSTABLE - PUSTULAR- LOCALISED & GENEREALISEDPUSTULAR- LOCALISED & GENEREALISED ERYTHRODERMICERYTHRODERMIC ARTHROPATHIC PSORIASISARTHROPATHIC PSORIASIS

PLAQUE PSORIASISPLAQUE PSORIASIS

PLAQUE PSORIASISPLAQUE PSORIASIS

PLAQUE PSORIASISPLAQUE PSORIASIS

AUSPITZ SIGNAUSPITZ SIGN

PSORIASIS OF PALMPSORIASIS OF PALM

PLAQUE PSORIASISPLAQUE PSORIASIS

PLAQUE PSORIASISPLAQUE PSORIASIS

PLAQUE PSORIASISPLAQUE PSORIASIS

PSORIASIS OF SCALPPSORIASIS OF SCALP

SCALP PSORIASISSCALP PSORIASIS

SCALP PSORIASISSCALP PSORIASIS

CLINICAL PICTURECLINICAL PICTURE

FLEXURAL PSORIASISFLEXURAL PSORIASIS

PUSTURAL PSORIASISPUSTURAL PSORIASIS

LOCALISED -LOCALISED - --THENER EMENECES & INSETP OF FOOT,THENER EMENECES & INSETP OF FOOT,

- MORE IN FEMALES,- MORE IN FEMALES, -NO ASSOCIATION OF HLA ANTIGENS-NO ASSOCIATION OF HLA ANTIGENS GENERALISED -GENERALISED - FEVER,MALASE, SEVER CONSTITUTIONAL FEVER,MALASE, SEVER CONSTITUTIONAL

SYMPTOMS,SYMPTOMS, PUSTULAR ERYTHEMA, FLUXERAL INVOLMENT,PUSTULAR ERYTHEMA, FLUXERAL INVOLMENT, TETANY,HYPOALBUMINAEMIATETANY,HYPOALBUMINAEMIA WITHDRAWAL OF STEROIDS,PREGNANCYWITHDRAWAL OF STEROIDS,PREGNANCY

PUSTULAR PSORIASISPUSTULAR PSORIASIS

GENEREALIZED PUSTULAR GENEREALIZED PUSTULAR PSORIASISPSORIASIS

GUTTATE PSORIASISGUTTATE PSORIASIS

POST STREPTOCOCAL POST STREPTOCOCAL

BETA HAEMOLITICUSBETA HAEMOLITICUS

INFECTIONINFECTION USUALLY CHILDRENUSUALLY CHILDREN NO TYPICAL SCALESNO TYPICAL SCALES RESOLVE SPONTENOUSLYRESOLVE SPONTENOUSLY

GUTTATE PSORIASISGUTTATE PSORIASIS

EXTENSIVE PSORIASISEXTENSIVE PSORIASIS

ERYTHRODERMIC PSORIASISERYTHRODERMIC PSORIASIS

HYPOTHERMIAHYPOTHERMIA

WATER & ELECTROLITE WATER & ELECTROLITE

BALANCEBALANCE

LOSS OF PROTEINLOSS OF PROTEIN

ANEMIAANEMIA

HYPERDYNAMIC HYPERDYNAMIC

CIRCULATIONCIRCULATION

NAIL PSORIASISNAIL PSORIASIS

NAIL PITTINGSNAIL PITTINGS

ONYCHOLYSISONYCHOLYSIS

SUBUNGUAL SUBUNGUAL

HYPERKERATOSISHYPERKERATOSIS

NAIL DYSTROPHIESNAIL DYSTROPHIES

NAIL PSORIASISNAIL PSORIASIS

NAL PITTINGSNAL PITTINGS

NAIL PSORIASISNAIL PSORIASIS

ONYCOLYSISONYCOLYSIS

NAIL PSORIAISNAIL PSORIAIS

NAIL PSORIASISNAIL PSORIASIS

PSORIATIC ARTHRITISPSORIATIC ARTHRITIS

SERONEGATIVE ATHRITISSERONEGATIVE ATHRITIS INCIDENCE- 1.5 TO 3%INCIDENCE- 1.5 TO 3% MALE FEMALE RETIO EQUALMALE FEMALE RETIO EQUAL HLA ASSOCIATION HLA B27,A26,B38,DR4,DR3HLA ASSOCIATION HLA B27,A26,B38,DR4,DR3 SKIN LESION PRECEDS IN 65% CASESSKIN LESION PRECEDS IN 65% CASES AGE OF ONSET- 40TO 60 YEARSAGE OF ONSET- 40TO 60 YEARS

CLINICAL TYPESCLINICAL TYPES

- - PREDOMINANTLY PERIPHERAL MONO OR PREDOMINANTLY PERIPHERAL MONO OR

OLIGO ARTHRITSOLIGO ARTHRITS

- DISTAL INTERPHALINGIAL ARTHRITIS- DISTAL INTERPHALINGIAL ARTHRITIS

-SYMMETRICAL RHEUMATOID LIKE ARTHRITS-SYMMETRICAL RHEUMATOID LIKE ARTHRITS

- ARTHRITIS MUTILANS- ARTHRITIS MUTILANS

-AXIAL ARTHRITIS-AXIAL ARTHRITIS

PSORIATIC ARTHROPATHYPSORIATIC ARTHROPATHY

PSORIASIS ARTHROPATHYPSORIASIS ARTHROPATHY

PSORIATIC ARTHRITISPSORIATIC ARTHRITIS

ARTHRITIS MUTILANSARTHRITIS MUTILANS

Which of the following statements regarding Which of the following statements regarding Psoriasis is correct?Psoriasis is correct? The prevalence in the UK is 10%The prevalence in the UK is 10% Psoriasis is more common at lower geographical Psoriasis is more common at lower geographical

altitudesaltitudes Guttate psoriasis is the most common form of the Guttate psoriasis is the most common form of the

diseasedisease 1% of patients have associated psoriatic 1% of patients have associated psoriatic

arthropathyarthropathy Psoriatic arthropathy precedes cutaneous lesions in Psoriatic arthropathy precedes cutaneous lesions in

29% of cases29% of cases

HISTOPATHOLOGYHISTOPATHOLOGY

HISTOPATHOLOGYHISTOPATHOLOGY

MICRO MUNRO ABSCES FORMATION IN EPIDERMISMICRO MUNRO ABSCES FORMATION IN EPIDERMIS

Which of the following statements regarding Which of the following statements regarding Psoriasis is most truePsoriasis is most true?? Diagnosis requires histological confirmationDiagnosis requires histological confirmation Guttate psoriasis often arises after staphylococcal Guttate psoriasis often arises after staphylococcal

infectioninfection T-cells play a prominent role in the pathogenesis T-cells play a prominent role in the pathogenesis

of psoriasisof psoriasis Ciclosporin is ineffective in the treatment of Ciclosporin is ineffective in the treatment of

psoriasispsoriasis Twin studies have identified no genetic basis for Twin studies have identified no genetic basis for

psoriasispsoriasis

MANAGEMENTMANAGEMENT GENERALGENERAL TOPICALTOPICAL - GAOECKERMAN’S REGIMEN – - GAOECKERMAN’S REGIMEN – 3 TO 6 % COAL TAR 3 TO 6 % COAL TAR

WITH UVAWITH UVA

-INGRAM’S REGIMEN --INGRAM’S REGIMEN -0.05 TO O.1% DIATHRANOL0.05 TO O.1% DIATHRANOL -TOPICAL VIT.D - -TOPICAL VIT.D - I Alfa,25-DIHYDROXY VIT.D 3I Alfa,25-DIHYDROXY VIT.D 3 CALCITRIOL CALCITRIOL CALCIPOTRIOL 50 CALCIPOTRIOL 50 MICROGRAMS/GRAMSMICROGRAMS/GRAMS TACALCITOL – 4 TACALCITOL – 4 MICROGRAMS/GRAMSMICROGRAMS/GRAMS

-TOPICAL CORTICO STEROIDS-TOPICAL CORTICO STEROIDS -TAZAROTENE-TAZAROTENE-TACROLIMUS-TACROLIMUS

PUVA THERAPYPUVA THERAPY

ULTRA VIOLATE (UV) RAYS – B 311nmULTRA VIOLATE (UV) RAYS – B 311nm UVA WITH PSORALINS - PUVAUVA WITH PSORALINS - PUVA

SYSTAMIC – 0.6mg/kg SYSTAMIC – 0.6mg/kg

LOCAL AS BATH 0.1 to 1 % solutionLOCAL AS BATH 0.1 to 1 % solution

PUVA THERAPYPUVA THERAPY

PUVA THERAPYPUVA THERAPYBEFORE AFTERBEFORE AFTER

UVB THERAPY

BEFORE

AFTER

REASONS TO CONSIDER REASONS TO CONSIDER SYSTEMIC THERAPYSYSTEMIC THERAPY

A 74-year-old man with a thirty year history of psoriasis A 74-year-old man with a thirty year history of psoriasis presented with generalised erythroderma of 3 days duration. presented with generalised erythroderma of 3 days duration. Examination reveals him to be shivering but otherwise is well. Examination reveals him to be shivering but otherwise is well. He was treated as an inpatient with emollients and attention to He was treated as an inpatient with emollients and attention to fluid replacement and temperature control but failed to fluid replacement and temperature control but failed to improve after five days. What is the most appropriate next improve after five days. What is the most appropriate next treatment?  treatment?   Oral hydroxychloroquineOral hydroxychloroquine Oral methotrexateOral methotrexate Oral prednisoloneOral prednisolone Topical coal tarTopical coal tar Topical dithranolTopical dithranol

SYSTAMIC THERAPYSYSTAMIC THERAPY

METHOTREXATE 7.5mg/ weekMETHOTREXATE 7.5mg/ week ORAL RETINOIDSORAL RETINOIDS CYCLOSPORIN 2.5mg/kg/dayCYCLOSPORIN 2.5mg/kg/day STEROIDSSTEROIDS BIOIMUNOLOGICAL AGENTSBIOIMUNOLOGICAL AGENTSINFLIXIMAB,ELALIZUMAB,ALEFAEPTINFLIXIMAB,ELALIZUMAB,ALEFAEPT

HYDROXYUREAHYDROXYUREA

METHOTREXATEMETHOTREXATE

INHIBITS DNA SYNTHESIS BY INHIBITS DNA SYNTHESIS BY

COMPETITIVE INHIBITION OF COMPETITIVE INHIBITION OF

DIHYDROFOLATE REDUCTASE ENZYMEDIHYDROFOLATE REDUCTASE ENZYME

S PHAGE SPECIFIC,S PHAGE SPECIFIC,

EXCERTION BY KIDNY,EXCERTION BY KIDNY,

LIVER CYCLING LIVER CYCLING

LIVERFIBROSISLIVERFIBROSIS

7-5 mg/week DIVIDED DOSES7-5 mg/week DIVIDED DOSES

EXTENSIVE PSORIASIS,EXTENSIVE PSORIASIS,

PUSTULAR PSORIASISPUSTULAR PSORIASIS

PSORIATIC ARTHROPATHYPSORIATIC ARTHROPATHY

ERYTHRODERMAERYTHRODERMA

RETINOIDSRETINOIDS

EETRETINATE 1mg/kgTRETINATE 1mg/kg

ISOTRETINOIN 0.5 to 1 mg/dayISOTRETINOIN 0.5 to 1 mg/day ACITRETIN 25 TO 50 mgACITRETIN 25 TO 50 mg ACT ON GROWTH & DIFFERENTIATION OF EPIDERMAL CELLSACT ON GROWTH & DIFFERENTIATION OF EPIDERMAL CELLS LIPOPHILIC HALF LIFE AS LONG AS 80 DAYSLIPOPHILIC HALF LIFE AS LONG AS 80 DAYS

SIDE EFFECTSSIDE EFFECTS TTERATOGENIC *****ERATOGENIC *****

INCEEAS SERUM LIPIDSINCEEAS SERUM LIPIDS LIVER TOXICITYLIVER TOXICITY DRYNESS OF LIPS EYES, MUCOSADRYNESS OF LIPS EYES, MUCOSACONTRAINDICATED IN PREGNANCYCONTRAINDICATED IN PREGNANCY

MECHANISM OF ACTION OF MECHANISM OF ACTION OF CYCLOSPORINCYCLOSPORIN

CYCLOSPORINCYCLOSPORIN FUNGUS- TALYPOCLADIUM INFLATUSFUNGUS- TALYPOCLADIUM INFLATUS INHIBITORY EFFECT OF T CELLS (IL2)INHIBITORY EFFECT OF T CELLS (IL2) EXTENSIVE, RESISTANT PSORIASISEXTENSIVE, RESISTANT PSORIASIS SIDE FEECTSIDE FEECT RENAL DYSFUNCTION,RENAL DYSFUNCTION, HYPERTENTIONHYPERTENTION GUM HYPERPLASIA,GUM HYPERPLASIA, HYPERTRICOSISHYPERTRICOSIS

PRECAUTIONSPRECAUTIONS PAST MALIGNANCYPAST MALIGNANCY ACUTE INFECTIONS,ACUTE INFECTIONS, NSAD THERAPYNSAD THERAPY

TACROLIMUSTACROLIMUS LEFLUNAMIDELEFLUNAMIDE BIOLOGICAL MODALITIESBIOLOGICAL MODALITIES

ETANERECEPT – 2TNFR+Fc OF IgGETANERECEPT – 2TNFR+Fc OF IgG INFLIXIMAB -- TNF alfaINFLIXIMAB -- TNF alfa ALEFACEPT CHIMERIC LFA -3 IgGALEFACEPT CHIMERIC LFA -3 IgG EFALIZUMAB BINDS TO ICAM -1EFALIZUMAB BINDS TO ICAM -1

TAZAROTENETAZAROTENE

DIFFERENTIAL DIAGNOSISDIFFERENTIAL DIAGNOSIS TINEA INECTIONTINEA INECTION DISCOID ECZEMADISCOID ECZEMA LICHEN SIMPLEX CHRONICUSLICHEN SIMPLEX CHRONICUS BOWEN’S DISEASEBOWEN’S DISEASE

COMPLICATIONSCOMPLICATIONS

PROGNOSIS -QUALITY OF LIFEPROGNOSIS -QUALITY OF LIFE