Complex Treatments in Dermatology Flashcards
what are complex therapies?
- high risk of toxicity
- narrow therapeutic window
- high cost
- specialised prescribing
- not first line treatments
what are examples of complex therapies?
- Isotretinoin in acne - reconatain
- Acitretin in psoriasis – not used as commonly
- Phototherapy in psoriasis sometimes in eczema aswell
- Ciclosporin and methotrexate in psoriasis and eczema
- Biologics in psoriasis (and eczema – dupilumab)
what is isoretinoin?
- for severe unresponsive acne
- consultation dermatologist prescription only
- 13-cis-retinoic acid
- reduced skin sebum excretion around 90% after 6 weeks
- decreases hyperkeratinisation
- anti-inflammatory response
what are the risks of isoretinion?
- have to avoid in pregnancy TERATOGENIC, cannot donate blood before during or after
- depression, anxiety and suicial ideation
- impaired night vision
- dry skin and mucous membranes
- makes skin very fragile, make sure to use UV protection and dont have any laser treatments
what are the NICE guidelines for treatment of psoriasis?
• Specialist treatment if symptoms severe, impact major, widespread (covering 10% BSA), and/or not controlled with topical therapy
• Use systemic therapy only if severe impact, cannot be controlled with topical therapy, AND one or more of:
o Extensive
o Functional impairment/distress high
o Phototherapy ineffective
• In some circumstances, use phototherapy first. Otherwise methotrexate first line if appropriate, or ciclosporin if specific conditions
what is phototherapy in psoriasis?
Narrowband UVB (NB-UVB)
• First line treatment
Psoralen and UVA (PUVA)
• Oral 8-methoxypsoralen (MOP-8) 0.6mg/kg
• Two hours before UVA exposure
• Disrupts DNA synthesis, inhibiting basal cell proliferation due to high turnover of cells
o Slows basal cell growth to normal
• Treatment 3 x weekly
• Clears in 5 to 6 weeks (20-30) exposures – not a long term treatment
what are the risks of phototherapy?
• Adverse effects
o Teratogenic (MOP), premature skin ageing, skin pigmentation, cataract formation
• Precautions
o Effective contraception, UVA eye protection, regular skin examinations for pre- / malignant changes
o History of cancer have to avoid as it increases risk of cancer and the more treatments you have the greater the risk
what is aciterin used for in psoriasis?
• Synthetic Retinoid
• Decreases hyperkeratinisation
o Normalises skin cell proliferation, differentiation and cornification
• Side-effect profile similar to isotretinoin BUT longer half-life and prolonged therapy needed in psoriasis
what are the risks of acitetin/
• Contraception in women of child-bearing potential for 3 years after taking
o (pregnancy prevention programme, PPP)
• Hyperlipidaemia
o cardiovascular risk assessment needed
o monitoring of lipid profile
• Hepatotoxic
o Monitor liver function every 3/12 during treatment (more frequently at start)
o Do not drink alcohol or keep to absolute minimum and for 2 months after
Increases serum level concentration
how does methotrexate work is psoriasis?
• Folic acid antagonist
o inhibits dihydrofolate reductase
• Blocks DNA synthesis (folates co-factors for many enzymes)
o slows basal cell proliferation in psoriasis
• Enzyme inhibition leads to increased adenosine which inhibits neutrophil chemotaxis and cytokine secretion
o anti-inflammatory action in eczema
• Takes 1-3 months for full effect to be seen at optimal dose
o Expectation setting important
what are the risks of methotrexate?
- liver cirrhosis so need to carry our liver function tests every month
- can cause blood disorders - so take full blood count every week
- GI symptoms
- alopecia, family planning and increased infection risk
how does ciclosporin work in psoriasis?
blocks calcineurin-dependent factors
- interleukin 2 blocked
- proliferation of T lymphotcytes and cytokines blocked
- proliferation of keratinocytes blocked
what are the risks of ciclosporins?
• Nephrotoxic - Monitor renal function • Hypertension - Monitor blood pressure • Teratogenic - Contraception, although ciclosporin may be used as a last line for pregnancy as it is the least risk to the baby • Immunosuppressant - Infection risk - Flu, fever, uclers, bleeding or bruising all could indiciate something is wrong - No live vaccines - Avoid grapefruit juice
how do biologics work in psoriasis?
- etanercept genetically engineered fusion protein , very expensive
- infliximab, adaliumumbab, these are anti-TNF monoclonal antibodies
- highly effective usually see a response within 6 weeks
how are the biologics administered?
• Etanercept = twice weekly; s/c injection =?combine with methotrexate = Data support use up to 2 years • Infliximab =IV infusion at weeks 0, 2 and 6; then 8 weekly thereafter = Data support use up to 1 year; consider combination with methotrexate to reduce infliximab antibody formation s/c injection every other week • Adalimumab = s/c injection every other week = Data support use up to 1 year
