Complex treatment in dermatology Flashcards
What are complex therapies?
- High risk of toxicity
- High cost
- Intensive monitoring required
- Specialist prescribing (generally hospital consultant; not GP)
- NOT first line treatments; for moderate to severe treatment-resistant skin conditions
What is isotretinoin?
- For severe acne unresponsive to topical treatments and oral antibiotics
- Consultant dermatologist prescription only
How long (usually) is the course for isotretinoin?
16-week course usually sufficient
How does isotretinoin work?
- Reduces skin sebum excretion by ~90% after 6 weeks (causes apoptosis in sebocytes)
- Lowers P acnes concentrations on skin
- Decreases hyperkeratinisation
- interferes with comedogenesis
- Anti-inflammatory properties
Isotretinoin - risks?
- TERATOGENIC (pregnancy prevention programme, PPP)
o Effective contraception 1 month before treatment starts and 1 month after e.g. COC and condoms
o Cannot donate blood before, during or after. - Depression, anxiety, suicidal ideation
o Psychiatric history needed; STOP and refer to psychiatrist if mental health deteriorates on treatment - Impaired night vision
o Inform DVLA if affected; do not drive at night
o Contraindicated in pilots. - Dry skin and mucous membranes, joint pains common
- Makes skin very fragile
o Need UV protection in summer – SPF 50
o NO wax epilation, dermabrasion or laser treatments during
What do you need to consider with complex therapies in psoriasis?
Age, treatment history, disease type, disease severity, impact arthritis, contraception plans, co morbidities, patients personal views
NICE guidelines for complex 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
Describe the two types of phototherapy in psoriasis:
Narrowband UVB (NB-UVB) - First line treatment
Psoralen and UVA (PUVA)
Oral 8-methoxypsoralen (MOP-8) (most common) 0.6mg/kg
What is PUVA?
Oral 8-methoxypsoralen (MOP-8) (most common) 0.6mg/kg
- Two hours before UVA exposure
- Disrupts DNA synthesis, inhibiting basal cell proliferation
- Slows basal cell growth to normal
- Treatment 3 x weekly
- Clears in 5 to 6 weeks (20-30) exposures
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
What is acitretin (for psoriasis) and what are its risks?
- 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
Risks;
- Contraception in women of child-bearing potential for 3 years after taking
- (pregnancy prevention programme, PPP)
- Hyperlipidaemia
- cardiovascular risk assessment needed
- monitoring of lipid profile
- Hepatotoxic
- Monitor liver function every 3/12 during treatment (more frequently at start)
- Do not drink alcohol or keep to absolute minimum
How is methotrexate used in psoriasis (mode of actions)?
- 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
Methotrexate – risks?
- Can cause liver cirrhosis
- Liver function tests every month initially
- Can cause blood disorders
- Thrombocytopaenia, leucopaenia, anaemia
- Full blood count every week then monthly
- GI symptoms; stomatitis, nausea
- 5mg folic acid weekly (both drugs compete for cellular uptake so need to be taken separately)
- Other considerations
- Alopecia, family planning (teratogen), infection risk (avoid vaccinations or ensure they have them before)
- Interactions – trImethorpin, NSAIDs
How is cyclosporin used in psoriasis?
- Ciclosporin 2.5/kg DAILY (spilt into two doses)
- Blocks calcineurin-dependent factor
o Interleukin 2(IL2) blocked
o Proliferation of T-lymphocytes and cytokines blocked
o Proliferation of keratinocytes blocked
Ciclosporin – risks
Nephrotoxic
o Monitor renal function
Hypertension
o Monitor blood pressure
Teratogenic o Contraception (although ciclosporin can be reserved for use in pregnancy) not as teratogenic as others
Immunosuppressant
o Infection risk
Avoid grapefruit juice
How do biologics work in psoriasis?
- All target TNF
- Etanercept
o Genetically engineered fusion protein - Infliximab, adalimumab, and many more
o Anti-TNF monoclonal antibodies - Highly effective; response seen in 6 weeks
- Therapy continued for 6 months to 2 years (and sometimes beyond). Little data to support longer term use
Biologics – administration details (e.g. etanercept)
- twice weekly; s/c injection
- ?combine with methotrexate
- Data support use up to 2 years
Biologics – administration details (e.g. 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
Biologics – administration details (e.g. adalimumab)
- s/c injection every other week
- Data support use up to 1 year
Biologics - risks?
- Increased risk of infections
o Reactivation of latent TB particular concern
o TB screening and intermittent monitoring for symptoms
o Listeria and Salmonella risk
o Do not consume raw or part cooked, meat, fish, eggs or dairy products - Cardiovascular risk
o Do not use in severe heart failure and monitor patients with pre-existing
o CV disease closely - Worsening of neurological disease
o Do not use in demyelinating disease e.g. MS - Cancer risk – variety of types
How does dupilumab treat eczema?
- Monoclonal antibody that inhibits activation of T helper cells. These T helper cells disrupt the skin barrier by inhibiting expression of filaggrin and antimicrobial peptides.
- May predispose to worm infection, must ensure clear beforehand and suspend if present
- Other side effects/ cautions as per MABs
- NICE – use if no response/intolernace to MTX, AZA, CIC, myophenalate
- Dose every 2 weeks, review treatment if no response at 16 weeks
