Dr Fayyaz Chaudhri
• Maryport Health Services
• GPwSI
Solar (actinic) Keratosis
•
•
•
•
Background of solar elastosis
multiple flat or thickened
scaly or warty
skin coloured or reddened
lesions.
• cutaneous horn
www. dermnetnz.org
Treatment Options
• Cryotherapy
• Curettage & cautery
• Excision
• 5-Fluorouracil cream
• Imiquimod
• Photodynamic therapy
• Diclofenac gel
5-FU (efudix)
• useful when there are many lesions on
the face.
• applied once or twice daily for two to
four weeks.
• Expect inflammation - red, raw and
uncomfortable.
• Good end results
5-Fluorouracil : Mechanism of Action
5-fluorouracil is a structural analogue of Thymine and Uracil
with the 5-methyl group being replaced by fluorine.
Its activity can be explained by two mechanism:
F
Thymine
Uracil
Ref : Goette DK, J Am Acad Dermatol 1981;4(6):633-649
UK/EFU/12/0007
5-fluorouracil
5-Fluorouracil : Mechanism of Action
i)
Metabolite competition
5-FU competes with normal metabolites for access to
enzyme active sites and is eventually incorporated
into the host cell RNA molecules. These become
ineffective molecules for protein synthesis 1,2
ii) Enzyme inhibition
The 5-FU metabolite (5F-deoxyuridine monophosphate)
blocks the essential enzyme thymidylate synthetase
thus preventing DNA synthesis 1,2
Ref : Goette DK, J Am Acad Dermatol 1981;4(6):633-649
UK/EFU/12/0007
5-Fluorouracil : Mechanism of Action
Ineffective mRNA
F
F
5-FU
UK/EFU/12/0007
Triplet does not
code for an
amino acid t-RNA
5-Fluorouracil : Mechanism of Action
ii) Enzyme inhibition
Enzyme inhibition
Reduced DNA production
F
x
DNA replication
Making new copies for dividing cells
UK/EFU/12/0007
5-fluorouracil metabolite
inhibits thymidylate
synthetase
2 weeks after
Efudix treatment
5-Fluorouracil : Mechanism of Action
Therapeutic response depends
on severity of disease
•
•
Phase 1 - early, mild inflammation
transformed cells die by necrosis
leading to ....
Phase 2 - Severe inflammation
•
Phase 3 – lesion destruction and
macrophage clearance
•
Phase 4 – Scabbing, new tissue
production and healing process.
Ref: Litwin MS, Ryan RF Reed Ej et al. J Surg Oncol 1971;3:351-65
UK/EFU/12/0007
Excessive reaction
Imiquimod
• immune response modifier
• 2-3 times weekly for 4-12 weeks.
• inflammatory reaction,
• results are variable, but generally
excellent.
AK treated with IMIQUIMOD
4 WEEKS AFTER TREATMENT
Intraepidermal SCC – Bowens
scc