Dermatological diseases

Ahmed ShamanClinical Pharmacy Department

shaman@ksu.edu.sa

Psoriasis

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

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

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

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

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

Clinical Variants of Psoriasis

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

CLINICAL PRESENTATION

• Diagnosis of psoriasis is usually based on recognition of the characteristic plaque lesion, and not based on lab tests

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

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

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?

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)

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

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

Rationale for drug use

• Induce remission• Reduce the severity• Relieve symptoms

– Itch – Pain– Excessive scaling

Topical Therapy for Psoriasis

• Emollients• Keratolytics• Topical Corticosteroids• Coal Tars• Topical vitamin D analogues• Dithranol• Tazarotene• Topical immunomodulators

Emollients

• Soothing action• Apply liberally

Type Examples and propertieslight, nongreasy lotions—not usually moisturizing enough for atopic skin; often sting

slightly greasy aqueous cream—strength can be varied by adding liquid paraffin, white soft paraffin, olive oilproprietary 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 packwool alcohols ointmentproprietary preparations include DermaVeen Eczema cream, Eucerin, QV cream

very greasy liquid paraffin 50% and white soft paraffin 50% mix—rarely stings, spreads easilyemulsifying ointment—rarely stings, more difficult to spreadproprietary preparations include Dermeze, QV Intensive, QV Kids Balm

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%)

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

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

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

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

Classification of potencies of topical corticosteroids

Milddesonide 0.05%hydrocortisone 0.5%, 1%hydrocortisone acetate 0.5%, 1%Moderatebetamethasone valerate 0.02%, 0.05%clobetasone butyrate 0.05%methylprednisolone aceponate 0.1%triamcinolone acetonide 0.02%Potentbetamethasone dipropionate 0.05%betamethasone valerate 0.1%mometasone furoate 0.1%triamcinolone acetonide 0.1%Very potentbetamethasone dipropionate 0.05% in optimised vehicleclobetasol propionate 0.05%

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)

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

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

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

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

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

 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

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

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

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

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)

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

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

Biological Agents

Drug Target Type

adalimumab TNF alpha human monoclonal antibody

efalizumab CD11a of LFA1 humanised monoclonal antibody

etanercept TNF alpha soluble TNF alpha receptor

infliximab TNF alpha chimeric monoclonal antibody

Treatment of different types of psoriasisType of psoriasis Treatment options in order of common use

plaque—mild, moderate

tars, topical corticosteroids, calcipotriol, dithranol, tazarotene

plaque—widespread dithranol, tars, topical corticosteroids, phototherapy, methotrexate, acitretin, cyclosporin, biological agents

guttate penicillin, tars, topical corticosteroids, phototherapy, calcipotriol

flexural mild to moderate topical corticosteroids

erythrodermic hospitalisation, baths, emollients, methotrexate, acitretin, cyclosporin, biological agents

scalp—mild tar shampoo, topical corticosteroid lotions

scalp—severe tar or dithranol pomades, tar shampoo, systemic therapy

nail calcipotriol, potent topical corticosteroids, intralesional corticosteroids, systemic therapy

genital(adults, children) topical corticosteroids, tars

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 neck 7 g 10 g 10 g 15 g 20 g

arm and hand 7 g 10 g 15 g 20 g 30 g

leg and foot 10 g 15 g 20 g 30 g 55 g

trunk (front) 7 g 15 g 20 g 25 g 50 g

trunk (back and buttocks)

10 g 20 g 25 g 35 g 50 g

Based on twice daily application for 1 week