1. Dermatological diseases Ahmed Shaman Clinical Pharmacy Department shaman@ksu.edu.sa

2. Psoriasis

3. It is a chronic inflammatory illness that is never cured Signs & symptoms may subside totally (go into remission) Return again (flare-up, exacerbation, or reactivation) Remission may last for years in some patients, while in others exacerbations may occur every few weeks

4. Psoriasis Clinical depression may be present in up to 60% of patients with psoriasis Poor self-esteem, anxiety and sexual dysfunction Associated with heart disease, diabetes, and the metabolic syndrome ↑Incidence of inflammatory bowel diseases, such as Crohn’s and ulcerative colitis One-third of patients have associated arthritis

5. Psoriasis Patients with psoriasis have a lifelong illness that may be very visible and emotionally distressing Empathy and a caring attitude in interactions with these patients

6. Psoriasis Keratinocyte proliferation is central to the clinical presentation of psoriasis (hyperkeratosis) Psoriasis is a T-lymphocyte–mediated inflammatory disease that results from a complex interplay between multiple genetic factors and environmental influences Genetic predisposition coupled with some precipitating factor triggers an abnormal immune response, resulting in the initial psoriatic skin lesions

7. Clinical Variants of Psoriasis Plaque psoriasis (Psoriasis Vulgaris) – Dry, scaling plaque with erythema Guttate psoriasis – Small ‘drop-like’ plaques often after strept. or viral infection Flexural psoriasis – Smooth inflamed lesion at flexural surfaces Erythrodermic psoriasis – Widspread loss of fine scales, severe itching and pain Pustular psoriasis – Localised or generalized pus-like blisters, non-infectious Scalp psoriasis Nail psoriasis Genital psoriasis

8. Clinical Variants of Psoriasis

9. Plaque psoriasis (Psoriasis Vulgaris) The most common type of psoriasis About 90% of psoriasis patients Most common dermatological reason for hospital admission One peaks of onset: age 16 to 22 years – more severe, therapy-resistant, strongly familial psoriasis Second peak: 57 to 60 years – Family history may be absent and the disease may be milder

10. CLINICAL PRESENTATION Diagnosis of psoriasis is usually based on recognition of the characteristic plaque lesion, and not based on lab tests

11. CLINICAL PRESENTATION Lesions (plaques) – Well demarcated, Red-violet Erythematous plaques with white to silver scales – Vary in thickness and sizes Symptoms – Patients may complain of severe itching (50%) – Excoriations from constant scratching Most commonly affected site – Elbows, knees, scalp, umbilicus, and lumbar areas – Extend to involve the trunk, arms, legs, face, ears, palms, soles, and nails

12. Diagnostic Features Auspitz’s sign – Diagnostic for psoriasis – Pinpoints of bleeding when scales removed Koebner phenomenon – Occurrence at a site of skin trauma Horse-fly bite Surgical scar Burn

13. Case A 25-year-old Caucasian man presents with itchy lesions on his scalp, chest, back, elbows, and knees. He says these lesions started about a month ago, and seem to be spreading. Upon examination, the lesions are well demarcated and are reddish-violet in color—easily distinguished from normal skin. They appeared raised and are covered with loose scales. Scales are silvery in color. Removing the scales caused pinpoints of bleeding to show up. There are signs of excoriation on the patient’s chest. What information is consistent with psoriasis in this patient?

14. Assessment Relative rating of presentation – Mild, moderate and severe Measures of symptom Body surface area (BSA) Psoriasis Area Severity Index (PASI) Dermatology Life Quality Index (DLQI) Short Form (SF-36) Health Survey Physician's Global Assessment (static PGA)

15. Predisposing and Precipitating Factors Skin injury – Mechanical, UV or chemical Infections – Viral, HIV, streptococcal Emotional – Stress Smoking & alcohol Drugs – NSAIDS (indomethacin) – Lithium Chloroquine, hydroxychloroquine and interferon α – Beta blockers & some ACEIs – withdrawal of systemic and potent topical corticosteroids

16. TREATMENT Minimise or eliminate potential triggers Nonpharmacologic – Stress reduction techniques – Oatmeal baths – Nonmedicated moisturizer – Avoid irritant chemicals on the skin – Avoid skin trauma Pharmacologic – Topical – Phototherapy – Systemic

17. Rationale for drug use Induce remission Reduce the severity Relieve symptoms – Itch – Pain – Excessive scaling

20. Topical Therapy for Psoriasis Emollients Keratolytics Topical Corticosteroids Coal Tars Topical vitamin D analogues Dithranol Tazarotene Topical immunomodulators

21. Emollients Soothing action Apply liberally TypeExamples and properties light, nongreasylotions—not usually moisturizing enough for atopic skin; often sting slightly greasyaqueous cream—strength can be varied by adding liquid paraffin, white soft paraffin, olive oil proprietary preparations include Cetaphil cream moderately greasy glycerol 10% in sorbolene cream—use formulations in a tub or tube as more moisturising and less likely to sting than formulations in a pump pack wool alcohols ointment proprietary preparations include DermaVeen Eczema cream, Eucerin, QV cream very greasyliquid paraffin 50% and white soft paraffin 50% mix—rarely stings, spreads easily emulsifying ointment—rarely stings, more difficult to spread proprietary preparations include Dermeze, QV Intensive, QV Kids Balm

22. Keratolytics Soften and remove scale Salicylic acid is the most commonly used and is compounded in an ointment or cream base – Salicylic acid breaks down keratin Rx – Salicylic acid 2% to 10% in sorbolene cream, emulsifying ointment or white soft paraffin topically, once or twice daily Adverse effects – Irritation, burning – Sensitivity to salicylic acid → lactic acid (1-10%)

23. Tars Preparations Anti-inflammatory and antipruritic effect First-line therapy Use is declining – limited patient acceptability (colour and odour) Available as ointments, creams, and shampoos in various strengths Rx – 2% to 10% cream or ointment topically, twice daily Adverse effects – May precipitate folliculitis – Photosensitivity

24. Dithranol Antiproliferative effect on keratinocytes Thick plaque psoriasis Unstable to oxidation Burn unaffected skin→ Not for face, flexures or genitals – Normal skin protected by using paste or zinc oxide – Wear gloves

25. Dithranol Lower concentrations are used in a long-contact regimen – Dithranol 0.1% to 1% with salicylic acid 2% to 5% (to prevent oxidation and remove scale) in yellow soft paraffin topically to lesions with care, once daily Higher concentrations are used in a short-contact regimen – Dithranol 1% to 4% (or occasionally up to 5%) with salicylic acid 2% to 5% topically to lesions with care, once daily for 10 to 30 minutes before washing off. – The contact period is progressively increased according to tolerance

26. Topical Corticosteroids Anti-inflammatory and antimitotic effects Mild steroids – Face, flexures, groins, children & elderly Moderate steroids – Mild-moderate plaques & eczema Potent steroids – More severe presentation of psoriasis & eczema Very potent steroids – Thicker areas of skin or thicker plaques of psoriasis – Often for severe hand & foot psoriasis

27. Classification of potencies of topical corticosteroids Mild desonide0.05% hydrocortisone0.5%, 1% hydrocortisone acetate0.5%, 1% Moderate betamethasone valerate0.02%, 0.05% clobetasone butyrate0.05% methylprednisolone aceponate0.1% triamcinolone acetonide0.02% Potent betamethasone dipropionate0.05% betamethasone valerate0.1% mometasone furoate0.1% triamcinolone acetonide0.1% Very potent betamethasone dipropionate0.05% in optimised vehicle clobetasol propionate0.05%

28. Adverse effects of topical corticosteroids Loss of dermal collagen – Skin atrophy, formation of striae, fragility and easy bruising, easily lacerated skin Telangiectasia – Development of prominent blood vessels Promotion of underlying infection Idiosyncratic reactions – Allergic contact dermatitis, perioral dermatitis Absorption of more potent agents applied to large areas may cause suppression of the hypothalamic-pituitary axis (Problems in children)

29. Vitamin D analogues Calcipotriol, calcitriol, and tacalcitol Regulates proliferation and differentiation of keratinocytes Effective in psoriasis but slow to work At least 4-6 weeks after therapy is initiated Rx – Calcipotriol (50 mcg/g) topically, twice daily Using more than 100 g per week can result in hypercalcaemia Erythema and irritation, especially on the face and flexures – Combine with potent steroid

30. Tazarotene Topical retinoid Normalizes keratinocyte differentiation and has antiproliferative and anti-inflammatory effects Available as 0.05% and 0.1% cream Daily application in the treatment of chronic plaque psoriasis Local irritation is a common problem – Combining with a topical corticosteroid helps to reduce irritation and enhance efficacy Avoid its use in women of child-bearing age unless effective contraception is being used

31. Phototherapy for Psoriasis Phototherapy or photochemotherapy is used for patients with moderate to severe psoriasis Photochemotherapy is the concurrent use of phototherapy together with topical agents or systemic drugs Involves the use of either ultraviolet A (UVA) or UVB

32. Phototherapy for Psoriasis UVA is a longer wavelength, combined with psoralens (PUVA) – Methoxsalen or trioxsalen – Photosensitizers to increase efficacy UVB therapy (using narrow- or broad-band UVB light) They are often combined with other treatments to reduce cumulative UV exposure – Calcipotriol, tazarotene, acitretin

33. Phototherapy for Psoriasis Adverse effects – erythema, – Pruritus – Xerosis – Hyperpigmentation – Blistering Risk of non-melanoma skin cancer with – PUVA – The risk with UVB therapy is unclear

34. Systemic Therapy Acitretin Methotrexate Cyclosporin Biological therapies  Generally reserved for patients with moderate to severe psoriasis  Rotational therapy to minimize drug toxicities  Rotating fashion  Methotrexate–acitretin–cyclosporine or methotrexate–PUVA– acitretin  Sequential therapy  Starting with systemic therapy followed by topical therapy

35. Acitretin Affects mechanisms of proliferation and differentiation, anti-inflammatory effect Pustular, erythrodermic and atypical presentations of psoriasis Safer than methotrexate or cyclosporine As monotherapy, the recommended dose is – Acitretin up to 0.5 mg/kg orally, once daily Increase the efficacy of phototherapy

36. Acitretin Teratogenic and pregnancy should be avoided during its use and for 2 years following cessation of therapy – Cheilitis – Hair shedding – photosensitivity – Elevated liver enzymes – Increased serum lipids

37. Methotrexate Slows epidermal cell proliferation and is an immunosuppressant Rx – Methotrexate 0.2 to 0.4 mg/kg (average 15 mg) orally, on one specified day per week Full blood count, renal and liver function should be regularly monitored Long-term use induce liver or pulmonary fibrosis Nausea, pancytopenia and elevation of liver enzymes – Reduced by the concomitant administration of folic acid folic acid 5 mg orally, once or twice weekly Preferably not on the day that the methotrexate is taken

38. Cyclosporin Immunosuppressant Good response rate Rx – Cyclosporin 1 to 2.5 mg/kg orally, twice daily (to a maximum of 5 mg/kg/day) Hypertension Deterioration of renal function Hirsutism, gingival hyperplasia Development of neoplasia (specifically skin squamous cell carcinoma and lymphoma)

39. Biological Therapies Parenteral medications target T cells or the pro-inflammatory cytokine TNF-α Response is variable but can be dramatic Very expensive Reactivation of latent infection (particularly tuberculosis) and possibly induction of malignancy

40. Biological Therapies Before starting treatment with immunosuppressants or TNF-alpha antagonists consider: – Presence of infection (including latent infection, eg hepatitis B, TB) – Immunisation requirements (especially for live vaccines) Give pneumococcal and annual influenza vaccinations – History of malignant disease

41. Biological Agents DrugTargetType adalimumabTNF alphahuman monoclonal antibody efalizumabCD11a of LFA1humanised monoclonal antibody etanerceptTNF alphasoluble TNF alpha receptor infliximabTNF alphachimeric monoclonal antibody

42. Treatment of different types of psoriasis Type of psoriasisTreatment options in order of common use plaque—mild, moderate tars, topical corticosteroids, calcipotriol, dithranol, tazarotene plaque—widespreaddithranol, tars, topical corticosteroids, phototherapy, methotrexate, acitretin, cyclosporin, biological agents guttatepenicillin, tars, topical corticosteroids, phototherapy, calcipotriol flexuralmild to moderate topical corticosteroids erythrodermichospitalisation, baths, emollients, methotrexate, acitretin, cyclosporin, biological agents scalp—mildtar shampoo, topical corticosteroid lotions scalp—severetar or dithranol pomades, tar shampoo, systemic therapy nailcalcipotriol, potent topical corticosteroids, intralesional corticosteroids, systemic therapy genital(adults, children)topical corticosteroids, tars

43. Suggested weekly quantities of topical preparations Age 3– 12 months Age 1– 3 years Age 3– 6 years Age 6– 10 years Age >10 years face and neck7 g10 g 15 g20 g arm and hand 7 g10 g15 g20 g30 g leg and foot10 g15 g20 g30 g55 g trunk (front)7 g15 g20 g25 g50 g trunk (back and buttocks) 10 g20 g25 g35 g50 g Based on twice daily application for 1 week