Complex treatments in dermatology Flashcards
What is Isotretinoin also known as?
Roaccutane
What is Isotretinoin used for?
Severe acne unresponsive to topical treatments and oral antibiotics
How can you get Isotretinoin?
Consultant dermatologist only: 16-week course usually sufficient
What is isotretinoins active ingredient?
13-cis-retinoic acid (at least 5 biologically active metabolites
How does isotretinoin work?
- Reduces skin sebum excretion by 90% after 6 weeks (causes apoptosis in sebocytes) –> lowers P acnes concentrations on the skin
- Decreases hyperkeratinisation (interferes with comedogenesis)
- Anti-inflammatory properties
How long is the Isotretinoin treatment?
- usually 16 weeks
- triple action
What are the risks of Isotretinoin?
- TERATOGENIC (pregnancy prevention programme, PPP)
- Depression, anxiety, suicidal ideation
- Impaired night vision
- Dry skin and mucous membranes, joint pains common - reduces bodily secretions
- makes skin very fragile
What needs to be taken into account given the teratogenicity of Isotretinoin?
- Effective contraception 1 month before treatment starts and 1 month after e.g. COC and condoms
- Cannot donate blood before, during or after for a period of time
What needs to be taken into account given the risks of depression, anxiety and suicidal ideation of Isotretinoin?
- psychiatric history needed; STOP and refer to psychiatrist if mental health deteriorates on treatment
What needs to be taken into account given the risks of impaired night vision for Isotretinoin?
- inform DVLA if affected; do not drive at night
- contraindication in pilots
What needs to be taken into account given the risks fragile skin for Isotretinoin?
- need UV protection in summer - SPF 50
- NO wax epilation, dermabrasion or laser treatments during or 6/12 after
What do the NICE guidelines for psoriasis say about when specialist treatment should be used?
Specialist treatment if symptoms severe, impact major, widespread (covering 10% BSA), and/or not controlled with topical therapy
What do the NICE guidelines for psoriasis say about when systemic therapy should be used?
Use systemic therapy only if severe impact, cannot be controlled with topical therapy, AND one or more of:
- Extensive
- Functional impairment/distress high
- Phototherapy ineffective
In some circumstances, use phototherapy first. Otherwise methotrexate first line if appropriate, or ciclosporin if specific conditions
What are the 2 types of phototherapy in psoriasis?
- Narrowband UVB (NB-UVB)
- Psoralen and UVA (PUVA)
What is Narrowband UVB (NB-UVB)?
- first line treatment
- generally better tolerated
- treatment 2-3 times a week
What is Psoralen and UVA (PUVA)?
- Oral 8-methoxypsoralen (MOP-8) 0.6mg/kg
- 2 hours before UVA exposure
- Disrupts DNA synthesis, inhibiting basal cell proliferation (slows basal cell growth to normal)
- Treatment 3 times weekly
- Clears in 5 to 6 weeks (20-30) exposures
What are the adverse effects and precautions of Phototherapy?
Adverse effects:
- teratogenic (MOP), premature skin ageing, skin pigmentation, cataract formation
Precautions:
- Effective contraception, UVA eye protection, regular skin examinations for pre- / malignant changes
- History of cancer – avoid treatment as it can increase risk
What is Acitretin?
A synthetic retinoid used in psoriasis
What does Acitretin do?
- decreases hyperkeratinisation (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 using Acitretin?
- Contraception in women of child-bearing potential for 3 years after taking
- (pregnancy prevention programme, PPP) - Hyperlipidaemia (contraindicated)
- 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
What is Methotrexate used in?
Psoriasis and eczema
What is Methotrexate and what does it do?
- folic acid antagonist (inhibits dihydrofolate reductase)
- blocks DNA synthesis (folates co-factors for many enzymes)
- slows basal cell proliferation in psoriasis - enzyme inhibition leads to increased adenosine which inhibits neutrophil chemotaxis and cytokine secretion (anti-inflammatory action in eczema)
How long does it take for full effect of methotrexate to be seen at optimal dose?
1-3 months (dosing is WEEKLY)
What are the risks of methotrexate?
- 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 – on a different day to methotrexate as they compete for cellular uptake (can reduce effectiveness) - Other considerations
- Alopecia, family planning (teratogen), infection risk
What is ciclosporin used in?
Psoriasis and eczema
What is the dose for ciclosporin in psoriasis and eczema?
2.5/Kg DAILY (split into 2 doses)
What does ciclosporin do?
- Blocks calcineurin-dependent factor
- Interleukin 2(IL2) blocked
- Proliferation of T-lymphocytes and cytokines blocked
- Proliferation of keratinocytes blocked
What are the risks of ciclosporin?
- Nephrotoxic
- Monitor renal function - Hypertension
- Monitor blood pressure - Teratogenic
- Contraception - Immunosuppressant
- Infection risk
What do biologics in psoriasis target?
TNF
What biologics are used?
- Etanercept
- Genetically engineered fusion protein - Infliximab, adalimumab, and many more
- Anti-TNF monoclonal antibodies
How long does it take to see a response from biologics treatment?
Highly effective: response seen in 6 weeks
What are the risks of Biologics?
- Increased risk of infections
- Reactivation of latent TB particular concern
- TB screening and intermittent monitoring for symptoms
- Listeria and Salmonella risk
- Do not consume raw or part cooked, meat, fish, eggs or dairy products - Cardiovascular risk
- Do not use in severe heart failure and monitor patients with pre-existing CV disease closely - Worsening of neurological disease
- Do not use in demyelinating disease e.g. MS - Cancer risk
What is dupilumab?
- used in 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
