Transcript L7_Dermatological di..

Dermatological diseases
Ahmed Shaman
Clinical Pharmacy Department
[email protected]
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
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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
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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
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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
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Emollients
Keratolytics
Topical Corticosteroids
Coal Tars
Topical vitamin D analogues
Dithranol
Tazarotene
Topical immunomodulators
Emollients
• Soothing action
• Apply liberally
Type
Examples and properties
light, nongreasy lotions—not usually moisturizing enough for atopic skin; often sting
slightly greasy
moderately
greasy
aqueous cream—strength can be varied by adding liquid paraffin, white soft
paraffin, olive oil
proprietary preparations include Cetaphil cream
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
very greasy
proprietary preparations include DermaVeen Eczema cream, Eucerin, QV cream
liquid 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
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
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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
Mild
desonide
hydrocortisone
hydrocortisone acetate
Moderate
betamethasone valerate
clobetasone butyrate
methylprednisolone aceponate
triamcinolone acetonide
Potent
betamethasone dipropionate
betamethasone valerate
mometasone furoate
triamcinolone acetonide
Very potent
betamethasone dipropionate
clobetasol propionate
%0.05
%1 ,%0.5
%1 ,%0.5
%0.05 ,%0.02
%0.05
%0.1
%0.02
%0.05
%0.1
%0.1
%0.1
0.05% in optimised vehicle
%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)
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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
psoriasis
Type 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
scalp—mild
hospitalisation, baths, emollients, methotrexate, acitretin, cyclosporin,
biological agents
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
7g
10 g
10 g
15 g
20 g
arm and
hand
7g
10 g
15 g
20 g
30 g
leg and foot
10 g
15 g
20 g
30 g
55 g
trunk (front)
7g
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