Eczema and psoriasis Flashcards
Types of dermatitis (eczema)
• Primary irritant dermatitis - Caused by Chemical irritants • Allergic contact dermatitis - Caused by topically applied antigen • Atopic dermatitis - Most common type of eczema, cause unknown ?Emotional triggers inheritable? • Drug-related eczematous dermatitis - Response to systemic drug • Photoeczematous dermatitis - Caused by uv light
Mechanism of contact dermatitis
• Langerhans cell functions as an antigen presenting cell
• Activates naïve T cells in lymph nodes, which differentiate into memory T cells and effector T cells
• Memory T cells in skin recognise antigen on re-exposure
• Cytokine release by memory cells triggers effector T cell
recruitment
• Vascular endothelium is “activated” allowing further T cells recruitment
Psoriasis
- Red lesions, accompanied by skin forming as silver flakes (called scales, plaques or flakes)
- Most commonly back of elbows, knees and scalp
- Rapid turnover of the skin – 7 days instead of 56
- Thickened skin plaques with scales
- Dilation of capillaries
- Lymphocytes infiltrating
- Chronic condition, not curable
- May have prolonged periods of remission (years)
- Cause not well understood
- Not contagious
- Inflammation involved
- May be heritable component
Overview of pharmacotherapy for
eczema and psoriasis
• Eczema
– Emollients
– Topical corticosteroids (mild or potent depending on disease)
• Psoriasis – Phototherapy – Emollients – Coal tar – Retinoid » tazarotene topical » Acitretin Systemic po – Vitamin D analogs –calcipotriol, calcitriol tacalitol • Immune modifiers – Calcineurin inhibitors » Pimecrolimus tacrolimus – topical for eczema » Ciclosporin po for severe eczema or psoriasis – Methotrexate – severe psoriasis • Biologics - for severe unresponsive psoriasis – Etanercept – Adalimumab – infliximab – Ustekinumab
Coal tar
- For treatment of psoriasis
- Produced from distillation of coal
- Very complex mixture – numerous chemicals
- Mechanism unclear
- relieves itching
- “keratolytic” -breaks down keratin – helps reduce skin thickening
- Cocois
- Coconut oil containing coal tar, salicylic acid and sulfur
Tacrolimus & Pimecrolimus
- Indicated when corticosteroids inadequate/inappropriate
- Pimecrolimus – mild/moderate eczema
- Tacrolimus – moderate/severe eczema
PK
• Topical administration
• Relatively little systemic exposure, but is metabolized by Cyp3A4
ADR
• Burning, pruritus – very common
Caution
• Relatively new drugs – safety still being assessed
• Increased risk of skin infection? (why?)
• Increased risk skin cancer, lymphoma ?
• Avoid exposure to UV light (stay in shade, avoid tanning) – potential
increased risk of cancer?
Contraindications
• Hypersensitivity – including other macrolides 14-16 membered lactone ring (eg erythromycin, sirolimus)
• Skin barrier defects
• avoid in immunodeficiency
Drug interactions
• Avoid with other immunosuppressants
Ciclosporin
- “Older” calcineurin inhibitor for severe eczema or psoriasis
- Similar mechanism of action but signficant ADR
PK
• P.o; F~ 30% and t½ ~18 hr but variable
• Cyp 3A4 substrate
ADR
• Can be severe! Esp. nephrotoxicity & hypertension
• Also neurotoxicity, hepatotoxicity, hyperlipidaemia, neoplasms, infection
Caution
• Avoid UV light
• Monitor renal function
• Existing infections
Contraindications
• Hypersensitivity
• Poor renal function, hypertension, uncontrolled Infection, cancer
Drug interactions
• Avoid with other immunosuppressants
• Cyp3A4 substrates, inducers, inhibitors
Methotrexate
- Inhibits dihyrofolate reductase
- “antimetabolite” used to treat cancer
- used for severe psoriasis
- Mechanism in psoriasis unclear
- Decreased nucleotide synthesis?
- Increased apoptosis of T cells
- Increase in adenosine is antiinflammatory
PK
• Low dose po once weekly!
• Elimination
• tubular secretion by OAT3
ADR
• Bone marrow suppression & Blood dyscrasia
• (abnormality in production of any blood cell type)
• Hepatoxicity (at high dose)
• Nephrotoxicity (at high dose)
• GI ulceration
• Risk of infection
• Blood counts, liver, renal function tests recommended
Caution • Impaired liver function • Blood disorder • GI ulceration • Impaired renal function
Drug interactions • NSAIDS » inhibit tubular secretion » Both compete for OAT3 • Antifolate antibiotics » risk of additive toxicity » Both inhibit folate synthesis
Contraindications
• Severe renal or hepatic impairment
• Pregnancy & lactation- teratogenic
Steroids – a reminder
• Adrenal cortex steroids = “corticosteroids” • Glucocorticoids (glucocorticosteroids) » regulate protein and carbohydrate metabolism » Anti-inflammatory » Eg hydrocortisone and corticosterone • Mineralocorticoids » Regulate fluids/electrolytes » Eg aldosterone. See diuretics lecture
• Sex steroids
- Androgens eg testosterone
- Estrogens eg estradiol
• Cholesterol
-Membrane fluidity
Glucocorticoid - mechanism of action
• Inhibition of inflammatory gene expression (COX2, NO synthase, TNFa, IL1)
• Induction on anti-inflammatory gene expression (annexin 1)
• Inhibition of leukocyte migration and activity
• Inhibition of prostanoid/leukotriene synthesis
• Inhibition of T lymphocyte proliferation (reduced IL2 etc.
production)
- Topical glucocorticosteroids - first line therapy for atopic eczema
- Anti-inflammatory, Vasoconstriction
- Inhibit keratinocyte proliferation
- 4 classes (others distinguish 7 classes)
- Mild (e.g. hydrocortisone); Moderate (e.g. betamethasone valerate); Potent (e.g. budesonide); Very Potent (e.g. clobetasol propionate)
- NB: different salts exhibit different potencies, some are systemically absorbed, others less so
- Topical application preferred
- Modest improvement in efficacy with systemic routes, but do get additional ADR
- Systemic route only for v. severe/life threatening cases, e.g. allergic contact dermatitis with poison ivy
Glucocorticoids (3)
• ADR with systemic therapy
– Inhibition of hypothalamic/pituitary/adrenal axis
» Chronic use depresses ACTH which regulates cortisol production
by adrenal gland (adrenal insufficiency)
» Gradual withdrawal helps prevent disease flaring up during withdrawal
– weight gain and diabetes mellitus
» Stimulate gluconeogenesis and inhibit Glc uptake by liver/muscle
– Redistribution of fat
» Fat breakdown my some tissues, accumulation in others
– Broad anti-inflammatory effects
» Reduced production of inflammatory cytokines –reduced cellular response
» Impaired vascular response to damage (inhibit dilation &
permeability that leads to oedema) so reduced extravasation
– Hypertension
» Cortisol regulates bp
CRF
ACTH
Cortisol
-(when cortisol is used therapeutically, it’s called hydrocortisone)
Glucocorticoids (4)
• ADR with topical therapy
• The ADR associated with systemic use are less common with topical therapy unless large area treated with drug or potent steroid used
• However, may see:
» Thinning of skin and telangiectasia may be unsightly
» Acne
Caution
• Short term use
• Avoid potent glucocorticoids in psoriasis –possibility of rebound relapse
Contraindications
• Uncontrolled infections
Retinoids
- normalize abnormal growth and differentiation in keratinocytes
- Alitretinoin
- for eczema
- Tazoretene
- for psoriasis
- Topical
- Acitretin
- For severe psoriasis
- p.o
ADR/ Cautions/ Contraindications
• Topical
• burning, erthymea
• Retinoids are teratogenic
• Systemic retinoids are contraindicated in pregnancy
• Topical retinoids should be avoided.
• Acitretin contraindicated in hyperlipidaemia and should be avoided in hepatic and renal impairment
Vitamin D analogues examples
- Calcipotriol, Calcitriol, Tacalcitol
- For psoriasis – mostly commonly prescribed drugs for psoriasis
- Calcitriol is active metabolite of vitamin D
- Vitamin D production is catalysed by uv light (also used as a psoriasis treatment)
Vitamin D analogues
• ADR + Contraindications
ADR
• Skin reactions common: burning, erythema, pruritus, paraesthesia
• Hypercalcaemia
• (vitamin D stimulates Ca2+ absorption from small intestine)
• Risk increased if exposed to uv light too
Contraindications
• Ca2+ metabolism disorders
