Dermatological diseases

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

2. Psoriasis

3. Psoriasis • 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

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 • Antiproliferativeeffect on keratinocytes • Thickplaque 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 • Dithranol0.1% 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 • Dithranol1% 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

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 • Teratogenicand 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) • Immunisationrequirements (especially for live vaccines) • Give pneumococcal and annual influenza vaccinations • History of malignant disease

41. Biological Agents

42. Treatment of different types of psoriasis

43. Suggested weekly quantities of topical preparations Based on twice daily application for 1 week