Psoriasis

An educational, informative presentation on psoriasis. It covers the latest pathogenesis of the disease and treatment guidelines. the differential diagnosis is well defined.

1. Psoriasis Dr. Ayshah Hashimi

2. History about Psoriasis It’s a Greek word “Psora” meaning Itchy Hkm. Jalinoos (Galen) referred this term to all the epidermopathies with pruritis Earlier it was thought that psoriasis was a  genetic disease  that is triggered by environmental factors According to the pathogenesis dermatologist considered it an epidermal disorder in which fundamental defect resided within Keratinocytes Earlier it was believed that decrease epidermal turnover time (10 days) was the main cause that result in immature hyperproliferation of keratinocytes

3. Introduction to Psoriasis L ong-lasting or chronic Noncontagious or non- infectious Inflammatory Autoimmune disease Characterized by  raised areas of abnormal skin due to decrease epidermal turnover time or increase in production of epidermal cells at a rate that is about six to nine times faster than normal These areas are  red , or purple on some people with darker skin,  dry ,  itchy , and scaly Psoriasis varies in severity from small, localized patches to complete body coverage Injury to the skin can trigger psoriatic skin changes at that spot, which is known as the  Koebner phenomenon Areas of the body most commonly affected are the back of the forearms, shins, navel area, and scalp Nails are affected ( pits in the nails or changes in nail color )

4. Prevalence 1-3% affected but 50% requires instant aggressive treatment Common in both the sexes Disease exaggerate in winters Develop at any age but two peaks are seen Early onset: Incidence in 3 rd decade Genetic association observed (HLA-Cw6) Positive family history More severe Presence of arthropathy Late onset: Peak incidence in 5 th decade Less frequent family history Milder course

5. Etiology/ Provoking factors Idiopathic Genetic Autoimmune reactions Infection (streptococcal antigen provokes guttate psoriasis) Injury to skin ( Kobernization occurs) Endocrine factors (puberty and menopause) confirmation required for endocrinological etiologies UV rays (favorable in some as they depletes lymphocytes while precipitates in some cases) Metabolic syndromes (hyperlipidemias, thyroid dysfunction, DM, obesity) certainly contributes to the progression of the disease Medication (Lithium, β adrenergic blockers, anti-depressants, antimalarials and sudden withdrawal of corticosteroids)

6. Pathogenesis The disease had been considered hyperproliferative disorder and various treatment modalities which were used for the treatment had antiproliferative actions. Molecular techniques have given new views regarding the pathogenesis of the disease So, according to the evidences psoriasis is a T-cell mediated inflammatory disease as Both CD4+ and CD8+ t lymphocytes accumulates in the diseased skin Various new treatment modalities are available as the revised pathogenesis is a bit different from the traditional one During genetics screening, 8 loci have been identified which are linked to the pathogenesis of the disease

7. Gene Chromosome locus PSOR1 (major) 6p21.3 PSOR2 17q PSOR3 4q PSOR4 1q PSOR5 3q PSOR6 19q PSOR7 1p PSOR8 16q p is short arm while q is long arm of chromosome PSOR1 is most common of all also its been observed that psoriasis vulgaris and guttate psoriasis are genetically identical

8. Cardinal features of psoriasis Epidermal hyperproliferation with loss of differentiation/ maturation Clinical appearance is largely caused by epidermal changes, the disease has traditionally been considered as a disorder associated with excessive keratinocyte proliferation and abnormal maturation. It was believed that epidermal turnover time was reduced to approx. 8 folds According to recent studies increase proliferation is due to increase in the proliferating cell compartment in the basal layer. No of cycling cells increase to 7 folds Psoriasis is a disease of interfollicular epidermis sparing har follicles Several growth factors are present in the lesion e.g. Transforming Growth Factor- α (TGF- α )

9. Cardinal features of psoriasis Dilatation and proliferation of dermal blood vessels Superficial microvasculature appears dilated and increases by four fold Chemokines by activated keratinocytes such as IL-8, TNF- α , vascular endothelial growth factor (VEGF) are involved in vascular changes In addition to vascular proliferation, they also contribute actively in the inflammatory process through surface expression of molecules to bring leucocyte into the skin In lesional skin, e-selectin and intracellular adhesion molecule-1 (ICAM-1) receptors is upregulated in affected capillaries due to effect of chemokines These receptors allow T-Lymphocyte to accumulate within the skin

10. Cardinal features of psoriasis Accumulation of inflammatory cells Before obvious changes apparent in skin epidermis, numerous lymphocytes appears CD+4, CD8+ & Langerhans cells (immature dendritic cell) increases in skin Epidermal keratinocytes in psoriatic lesion synthesize Human Leukocyte antigen (HLA) Cyclosporine has major inhibitory effect on T cell activation and thus improvement. Also, it has antiproliferative effect on keratinocytes In an experiment, it was observed that injection of T-lymphocytes in normal appearing skin induces psoriatic lesion CD8+ T cells are more in epidermis while CD4+ T cells are abundant in dermis Most T cells in skin lesion are memory cells with cutaneous lymphocyte antigen positive Dendritic cells produces IL-12 & IL-23 that activates T lymphocyte

11. Pathogenesis Any trigger in the skin stresses keratinocytes that releases DNA & RNA which binds with antimicrobial peptide called as Cathelicin 337 that activates innate immunity i.e. immature Langerhans cells to mature dendritic cell Activated Keratinocytes release IL4,6 and TNF- α Mature dendritic cell on activation enters circulation and reaches the draining lymph node and produces IL12 & IL23 In the lymph nodes, under the influence of IL-12, T helper cells produces TH1 while IL-23 produces TH17 (activated T lymphocyte) T lymphocytes multiplies and enters the circulation and reaches the affected site (infiltration of lymphocytes) TH1 results in progresses inflammatory cascade by releases cytokines (Il-12, interferons etc.) while TH17 causes proliferation of keratinocytes and vascular changes and thus result in development of psoriatic lesion

12. Classification Chronic plaque psoriasis Guttate psoriasis Pustular psoriasis Chronic plaque psoriasis Guttate psoriasis Pustular psoriasis

13. Chronic plaque psoriasis/ Psoriasis vulgaris Commonest Mild Well-demarcated Indurated, erythematous (Pink to red plaque often surrounded by a hypopigmented halo called as Ring of Woronoff ) Itchy Loose (easily detachable), large, lamellar, silvery white scales (minimal in early lesion and absent in flexures and on glans) Discoid but at the site of trauma/scratch linear or irregular Size and no. varies Ring of Woronoff

14. Koebner’s or Isomorphic Phenomenon- Development of psoriatic lesion at the sites of trauma /scratch Grattage test: Scales in a psoriatic plaque can be accentuated (noticeable) by grating with a glass slide Au spitz Sign: A ppearance of punctate bleeding spots when psoriasis scales are scraped off Subdivision according to lesion Small plaque psoriasis Rupoid psoriasis (heaped-up papules) Subdivision according to site Flexural psoriasis (more in elderly females, erythematous plaque with minimal scaling) Scalp psoriasis (well-defined, indurated, spill beyond hair margin onto forehead and nape of neck) Genital psoriasis Psoriasis of palm & soles (bilateral, adherent scales)

15. Associated symptoms NAILS (30-50%) Pitting- deep irregular Discoloration of nail plate (yellow-brown) Subungual hyperkeratosis Onycholysis (separation of distal nail plate from nail bed, characteristically with erythematous proximal edge) Oil spots (salmon patch) Hyperkeratotic plaques on knuckles Musculoskeletal system 10% of patients with psoriasis have arthritis Metabolic association increase prevalence of hypertension, DM, insulin resistance, obesity, dyslipidaemias, CAD

16. Guttate psoriasis Children and adolescents Often precipitated by streptococcal infection Several small erythematous lesion with minimal scaling Usually present on trunk Pustular psoriasis Triggers due to misused if topical irritant or steroid therapy Diagnosis Exaggerate in winters Well-defined, erythematous, indurated, surmounted by loose silvery scales Usually present on pressure points, scalp, extensors Nail and joint involvement Positive grattage test and Auspitz sign

17. Differential Diagnosis Dermatitis Discoid lupus erythematous Pityriasis rosea Hand eczema Seborrheic dermatitis Onychomycosis

18. Features Dermatitis Psoriasis Morphology of lesion Ill-defined, exudative plaque with crust Well defined, erythematous, indurated, Silvery scales Itching Severe, oozes on scratch Variable, bleed on scratch Nail changes Not observed Pitting Distribution Acral parts Pressure points, scalp, extensors Dermatitis Psoriasis

19. Features Discoid Lupus Erythematous Psoriasis Morphology of lesion Annular plaques with scarring & depigmented in center Discoid, no scarring & depigmentation Scales Adherent Loose Sign + Carpet tack sign (horny plugs appears on scratch) + Auspitz sign Distribution Face, ear, scalp Pressure points, scalp, extensors Cause Exposure to sun No effect of sun exposure

20. Features Pityriasis rosea Psoriasis Course Self limiting (4-12 weeks) Chronic (on & off) Onset Large herald patch (80%) Slow progress Morphology of lesion Annular lesions Discoid Scales Collarette of scales Loose, silvery scale Distribution Trunk, parallel to ribs (Christmas tree pattern) Pressure points, scalp, extensors

21. Features Hand Eczema Psoriasis Itching Severe Variable Spillage beyond palm Absent Present Hyperkeratotic plaques on knuckles Absent present Erythema Less More Vesicles Frequently present Only if Postular Psoriasis Eczema

22. Features Seborrheic Dermatitis Psoriasis Morphology of lesion Ill-defined Well defined and erythematous Induration Minimal Present Spillage Absent Present Scales Greasy Silvery Nail changes Not observed Pitting Itching Severe Moderate

23. Features Onychomycosis Psoriatic Nail Morphology of lesion Asymmetrical, few nails involved Symmetrical, most of the nails involved Nail plate Thickened, tunneling Thickened and pitted Subungual Hyperkeratosis Friable Not friable KOH mount Positive Negative Psoriatic Nail Onychomycosis

24. Treatment Counseling Its not contagious Chronic disease with relapses and remissions Treating options are suppressive and not curative Topical agents Emollients (Vegetable or mineral Oil)- soften skin, hydrate skin (best used after hydration of lesions) Coal tar (3-6%)- anti-mitotic, anti-inflammatory (apply and expose to light) Dithranol (0.05%) reduces DNA synthesis Calcipotriol (0.005%) is antiproliferative, immunosuppressive and promotes differentiation Tazarotene(0.05%) is a retinoid which acts as keratolytic and keratoplastic Systemic agents are given only in case of severe cases Methotrexate 7.5-25mg/ week orally with Folic acid, 5mg after a day Acitretin (25-50mg) is an oral retinoid which inhibits cell growth and keratinization Cyclosporine 2.5-4mg/kg/day in two divided dose

25. Systemic steroids used in combination, gets instant results but sudden withdrawal causes pustular psoriasis Topical steroids Indications Mild to moderate steroids are used incase of lesion on face and genitals Potent steroids are used to in case of lesion on trunk and extremities Very potent steroid are used to treat lesion on palm and soles Advantages Effective Application and removal is easy Non-Irritant Disadvantages Long term use causes dermal atrophy and tachyphylaxis Results in early relapses

26. Phototherapy PUVA chambers Sun-exposure RePUVA (PUVA+ Acitretin) Biologics (used in severe cases only/ incase of no response/ Intolerance to systemic therapy/ disability Contraindicated in TB, viral hepatitis, cirrhosis, any life threatening disease, avoid vaccination during and post 6 months therapy) TNF- α Inhibitors Infliximab 5mg/kg IV at 0 week, 2, 6, 8 Etanercept 25mg biweekly SC for 24 weeks or 50mg biweekly for 12 weeks Adalimumab 80mg at 0 week, 40mg at 1 week IL-12/23 Inhibitors Ustekinumab 45-90mg SC at 0, 4,12 week (Stelara) IL-17 Inhibitors Secukinumab 300mg weekly for 4-5 weeks

27. Short synopsis of the Psoriasis It is a chronic T-cell mediated inflammatory disease of the skin characterize by erythematous plaques with loose greyish scales Males and females are equally affected Cause- Idiopathic but is immune mediated Genetic and certain medication (Lithium, β adrenergic blockers, anti-depressants, antimalarials and sudden withdrawal of corticosteroids) exaggerate the disease Pathogenesis confirms involvement of immune cells (Dendrites, T cell, NK cells etc.) and its manifestation on skin (hyperproliferation of keratinocytes without differentiation and maturation, discoid erythematous patches with loose silvery white scales) Treatment options are topical and systemic agents, photochemotherapy and Biologics

28. Assessment of Psoriasis severity According to PASI (Psoriasis Area And Severity Index) score According to Body Surface Area (BSA) Mild psoriasis <10% of BSA Moderate psoriasis 10-30% of BSA Severe psoriasis > 30% of BSA Grading Induration Erythema Scales No 0 No plaque No erythema No scaling Minimal 1 0.25mm plaque Faint erythema 5% od lesions have scale Mild 2 0.5mm plaque Light red Fine scales Moderate 3 0.75mm plaque Red Course scales Severe 4 >1mm plaque Dusky red Thick tenacious scales

29. Treatment guidelines for psoriasis MILD MODERATE SEVERE Psoriasis vulgaris Topical agents Topical agents + Phototherapy Topical agent + Systemic agent (no response observed, Biologics can be recommended) Facial Psoriasis Topical Tacrolimus/ Pimecrolimus (Immunosuppressive 0r Immunomodulator) Palmoplantar Psoriasis Topical steroid + Systemic agent Guttate Psoriasis Antibiotics + Topical agents +/ Phototherapy Pustular Psoriasis Topical agent + Systemic agent OR Topical steroid + Phototherapy