SHRI GANASAYA NAMAHA

AN UPDATE ON PSORIASIS BY DR. MAHESH MATHUR, MD,DVD,DCP (UK) MD,DVD,DCP (UK)

DEFINITION COMMON, CHRONIC COMMON, CHRONIC GENETICALLY DETERMINED GENETICALLY DETERMINED INFLAMATORY & PROLIFERATIVE INFLAMATORY & PROLIFERATIVE CHARACTERISED BY - Well defined, CHARACTERISED BY - 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 disease, morphology of lesions & duration of disease. - great variability in extent of disease, morphology of lesions & duration of disease.

EPIDEMIOLOGY INCIDANCE & PREVELANCE INCIDANCE & 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 -I 5 TO 9 YEARS IN FEMALE- TYPE -I 15 TO 19 YEARS IN MALE- TYPE-1 15 TO 19 YEARS IN MALE- TYPE-1 30 TO 40 YEARS- TYPE II 30 TO 40 YEARS- TYPE II RACEAL DIFFERENCE RACEAL DIFFERENCE

AETIOLOGY & PATHOGENISIS INHERITED – NO SINGLE PATTERN, MULTIFACTORIAL INHERITED – NO SINGLE PATTERN, MULTIFACTORIAL MHC CLASS 1 –CW6- 80% ASSOCATION WITH TYPE I PSORIAIS MHC CLASS 1 –CW6- 80% ASSOCATION WITH TYPE I PSORIAIS FAMILIAL - TWIN SUDY – MONOZYGOT PAIR 73% FAMILIAL - TWIN SUDY – MONOZYGOT PAIR 73% DIZYGOTC PAIR 20 % DIZYGOTC PAIR 20 % 50% SIBLINGS IN PROBAND 50% SIBLINGS IN PROBAND WHEN BOTH PARANTS ARE AFFECTED

PROVOCATION & EXACERBATION TRAUMA TRAUMA INFECTION INFECTION ENDOCRIN FACTO- Pregnancy, Menopause ENDOCRIN FACTO- Pregnancy, Menopause SUN LIGHT SUN LIGHT METABOLIC METABOLIC DRUGS - lithium, beta blocker, antimalarials,systamic steroids DRUGS - lithium, beta blocker, antimalarials,systamic steroids PSYCOGENIC PSYCOGENIC ALCOHOL ALCOHOL AIDS AIDS

PATHOGENESIS T CELL MEDIATED T CELL MEDIATED KERATINCYTE PROLIFERATION KERATINCYTE PROLIFERATION HLA CW 6 HLA CW 6

IS IT AN IMMUNOLOGICAL DISEASE ?

YES ….. YES ….. CD4+ T CELLS IN DERMIS CD4+ T CELLS IN DERMIS CD8+ CELLS INFILTRATING IN EPIDERMIS – MHC I RESTRICTED CD8+ CELLS INFILTRATING IN EPIDERMIS – MHC I RESTRICTED MACROPHAGES & NEUTROPHILS INFILTRATION MACROPHAGES & NEUTROPHILS INFILTRATION IL1,IL6,IL8,TGF alfa,LTC4, C5a IL1,IL6,IL8,TGF alfa,LTC4, C5a IMMUNO THERAPY BY IMMUNO THERAPY BY METHOTRAXTE METHOTRAXTE

T CELL MEDIATED

PATHOLOGY & PATHOGENESIS KERATINOCYTE PROLIFERATIVE ACTIVITY- KERATINOCYTE PROLIFERATIVE ACTIVITY- VASODILATATION OF DERMAL VASSELS VASODILATATION OF DERMAL VASSELS * EIGHT FOLD SHORTENING OF EPIDERMAL CELL CYCLE * EIGHT FOLD SHORTENING OF EPIDERMAL CELL CYCLE * 36 ~311 h IN NORMAL * 36 ~311 h IN NORMAL *TWOFOLD INCRESE IN PROLIFERATIVE CELL POPULATION *TWOFOLD INCRESE IN PROLIFERATIVE CELL POPULATION *100% OF GERMINATIVE CELLS ENTER IN GROWTH FRACTION- 35,000 CELLS/ SQ.mm~1218 CELLS/SQ.mm *100% OF GERMINATIVE CELLS ENTER IN GROWTH FRACTION- 35,000 CELLS/ SQ.mm~1218 CELLS/SQ.mm

PATHOGENESIS

CLINICAL PRESENTATION CLINCAL VARIENT CLINCAL VARIENT PLAQUE PSORIASIS PLAQUE PSORIASIS GUTATE PSORIASIS GUTATE PSORIASIS FLEXURAL FLEXURAL NAPKIN PSORIASIS NAPKIN PSORIASIS UNSTABLE - UNSTABLE - PUSTULAR- LOCALISED & GENEREALISED PUSTULAR- LOCALISED & GENEREALISED ERYTHRODERMIC ERYTHRODERMIC ARTHROPATHIC PSORIASIS ARTHROPATHIC PSORIASIS

PLAQUE PSORIASIS

AUSPITZ SIGN

PSORIASIS OF PALM

PLAQUE PSORIASIS

PSORIASIS OF SCALP

SCALP PSORIASIS

CLINICAL PICTURE

FLEXURAL PSORIASIS

PUSTURAL 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 SYMPTOMS, FEVER,MALASE, SEVER CONSTITUTIONAL SYMPTOMS, PUSTULAR ERYTHEMA, FLUXERAL INVOLMENT, PUSTULAR ERYTHEMA, FLUXERAL INVOLMENT, TETANY,HYPOALBUMINAEMIA TETANY,HYPOALBUMINAEMIA WITHDRAWAL OF STEROIDS,PREGNANCY WITHDRAWAL OF STEROIDS,PREGNANCY

PUSTULAR PSORIASIS

GENEREALIZED PUSTULAR PSORIASIS

GUTTATE PSORIASIS POST STREPTOCOCAL POST STREPTOCOCAL BETA HAEMOLITICUS BETA HAEMOLITICUS INFECTION INFECTION USUALLY CHILDREN USUALLY CHILDREN NO TYPICAL SCALES NO TYPICAL SCALES RESOLVE SPONTENOUSLY RESOLVE SPONTENOUSLY

GUTTATE PSORIASIS

EXTENSIVE PSORIASIS

ERYTHRODERMIC PSORIASIS HYPOTHERMIA WATER & ELECTROLITE BALANCE LOSS OF PROTEIN ANEMIAHYPERDYNAMICCIRCULATION

NAIL PSORIASIS NAIL PITTINGS ONYCHOLYSISSUBUNGUAL HYPERKERATOSIS HYPERKERATOSIS NAIL DYSTROPHIES NAIL DYSTROPHIES

NAIL PSORIASIS NAL PITTINGS NAL PITTINGS

NAIL PSORIASIS ONYCOLYSIS ONYCOLYSIS

NAIL PSORIAIS

NAIL PSORIASIS

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

CLINICAL TYPES CLINICAL TYPES - PREDOMINANTLY PERIPHERAL MONO OR - PREDOMINANTLY PERIPHERAL MONO OR OLIGO ARTHRITS OLIGO ARTHRITS - DISTAL INTERPHALINGIAL ARTHRITIS - DISTAL INTERPHALINGIAL ARTHRITIS -SYMMETRICAL RHEUMATOID LIKE ARTHRITS -SYMMETRICAL RHEUMATOID LIKE ARTHRITS - ARTHRITIS MUTILANS - ARTHRITIS MUTILANS -AXIAL ARTHRITIS -AXIAL ARTHRITIS

PSORIATIC ARTHROPATHY

PSORIASIS ARTHROPATHY

PSORIATIC ARTHRITIS

ARTHRITIS MUTILANS

Which of the following statements regarding Psoriasis is correct? Which of the following statements regarding Psoriasis is correct? The prevalence in the UK is 10% The prevalence in the UK is 10% Psoriasis is more common at lower geographical altitudes Psoriasis is more common at lower geographical altitudes Guttate psoriasis is the most common form of the disease Guttate psoriasis is the most common form of the disease 1% of patients have associated psoriatic arthropathy 1% of patients have associated psoriatic arthropathy Psoriatic arthropathy precedes cutaneous lesions in 29% of cases Psoriatic arthropathy precedes cutaneous lesions in 29% of cases

HISTOPATHOLOGY

HISTOPATHOLOGY MICRO MUNRO ABSCES FORMATION IN EPIDERMIS MICRO MUNRO ABSCES FORMATION IN EPIDERMIS

Which of the following statements regarding Psoriasis is most true? Which of the following statements regarding Psoriasis is most true? Diagnosis requires histological confirmation Diagnosis requires histological confirmation Guttate psoriasis often arises after staphylococcal infection Guttate psoriasis often arises after staphylococcal infection T-cells play a prominent role in the pathogenesis of psoriasis T-cells play a prominent role in the pathogenesis of psoriasis Ciclosporin is ineffective in the treatment of psoriasis Ciclosporin is ineffective in the treatment of psoriasis Twin studies have identified no genetic basis for psoriasis Twin studies have identified no genetic basis for psoriasis

MANAGEMENT GENERAL GENERAL TOPICAL TOPICAL - GAOECKERMAN’S REGIMEN – 3 TO 6 % COAL TAR WITH UVA - GAOECKERMAN’S REGIMEN – 3 TO 6 % COAL TAR WITH UVA -INGRAM’S REGIMEN TO O.1% DIATHRANOL -INGRAM’S REGIMEN TO O.1% DIATHRANOL -TOPICAL VIT.D - I Alfa,25-DIHYDROXY VIT.D 3 -TOPICAL VIT.D - I Alfa,25-DIHYDROXY VIT.D 3 CALCITRIOL CALCITRIOL CALCIPOTRIOL 50 MICROGRAMS/GRAMS CALCIPOTRIOL 50 MICROGRAMS/GRAMS TACALCITOL – 4 MICROGRAMS/GRAMS TACALCITOL – 4 MICROGRAMS/GRAMS -TOPICAL CORTICO STEROIDS -TOPICAL CORTICO STEROIDS -TAZAROTENE -TAZAROTENE-TACROLIMUS

PUVA THERAPY ULTRA VIOLATE (UV) RAYS – B 311nm ULTRA VIOLATE (UV) RAYS – B 311nm UVA WITH PSORALINS - PUVA UVA WITH PSORALINS - PUVA SYSTAMIC – 0.6mg/kg SYSTAMIC – 0.6mg/kg LOCAL AS BATH 0.1 to 1 % solution LOCAL AS BATH 0.1 to 1 % solution

PUVA THERAPY

PUVA THERAPY BEFORE AFTER PUVA THERAPY BEFORE AFTER

UVB THERAPY BEFORE AFTER

REASONS TO CONSIDER SYSTEMIC THERAPY

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

SYSTAMIC THERAPY METHOTREXATE 7.5mg/ week METHOTREXATE 7.5mg/ week ORAL RETINOIDS ORAL RETINOIDS CYCLOSPORIN 2.5mg/kg/day CYCLOSPORIN 2.5mg/kg/day STEROIDS STEROIDS BIOIMUNOLOGICAL AGENTS BIOIMUNOLOGICAL AGENTSINFLIXIMAB,ELALIZUMAB,ALEFAEPT HYDROXYUREA HYDROXYUREA

METHOTREXATE INHIBITS DNA SYNTHESIS BY COMPETITIVE INHIBITION OF DIHYDROFOLATE REDUCTASE ENZYME S PHAGE SPECIFIC, EXCERTION BY KIDNY, LIVER CYCLING LIVERFIBROSIS 7-5 mg/week DIVIDED DOSES EXTENSIVE PSORIASIS, PUSTULAR PSORIASIS PSORIATIC ARTHROPATHY ERYTHRODERMA

RETINOIDS E TRETINATE 1mg/kg E TRETINATE 1mg/kg ISOTRETINOIN 0.5 to 1 mg/day ISOTRETINOIN 0.5 to 1 mg/day ACITRETIN 25 TO 50 mg ACITRETIN 25 TO 50 mg ACT ON GROWTH & DIFFERENTIATION OF EPIDERMAL CELLS ACT ON GROWTH & DIFFERENTIATION OF EPIDERMAL CELLS LIPOPHILIC HALF LIFE AS LONG AS 80 DAYS LIPOPHILIC HALF LIFE AS LONG AS 80 DAYS SIDE EFFECTS SIDE EFFECTS T ERATOGENIC ***** T ERATOGENIC ***** INCEEAS SERUM LIPIDS INCEEAS SERUM LIPIDS LIVER TOXICITY LIVER TOXICITY DRYNESS OF LIPS EYES, MUCOSA DRYNESS OF LIPS EYES, MUCOSA CONTRAINDICATED IN PREGNANCY

MECHANISM OF ACTION OF CYCLOSPORIN

CYCLOSPORIN FUNGUS- TALYPOCLADIUM INFLATUS FUNGUS- TALYPOCLADIUM INFLATUS INHIBITORY EFFECT OF T CELLS (IL2) INHIBITORY EFFECT OF T CELLS (IL2) EXTENSIVE, RESISTANT PSORIASIS EXTENSIVE, RESISTANT PSORIASIS SIDE FEECT SIDE FEECT RENAL DYSFUNCTION, RENAL DYSFUNCTION, HYPERTENTION HYPERTENTION GUM HYPERPLASIA, GUM HYPERPLASIA, HYPERTRICOSIS HYPERTRICOSISPRECAUTIONS PAST MALIGNANCY PAST MALIGNANCY ACUTE INFECTIONS, ACUTE INFECTIONS, NSAD THERAPY NSAD THERAPY

TACROLIMUS TACROLIMUS LEFLUNAMIDE LEFLUNAMIDE BIOLOGICAL MODALITIES BIOLOGICAL MODALITIES ETANERECEPT – 2TNFR+Fc OF IgG ETANERECEPT – 2TNFR+Fc OF IgG INFLIXIMAB -- TNF alfa INFLIXIMAB -- TNF alfa ALEFACEPT CHIMERIC LFA -3 IgG ALEFACEPT CHIMERIC LFA -3 IgG EFALIZUMAB BINDS TO ICAM -1 EFALIZUMAB BINDS TO ICAM -1 TAZAROTENE TAZAROTENE

DIFFERENTIAL DIAGNOSIS DIFFERENTIAL DIAGNOSIS TINEA INECTION TINEA INECTION DISCOID ECZEMA DISCOID ECZEMA LICHEN SIMPLEX CHRONICUS LICHEN SIMPLEX CHRONICUS BOWEN’S DISEASE BOWEN’S DISEASE COMPLICATIONS COMPLICATIONS PROGNOSIS -QUALITY OF LIFE PROGNOSIS -QUALITY OF LIFE