case studies in psoriasis - gp cme
TRANSCRIPT
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Dr Amanda OakleySpecialist Dermatologist, Dept of Dermatology, Health Waikato
Webmaster, DermNet NZ, NZ Dermatological SocietyClinical Associate Professor, Waikato Clinical School
Specialist Dermatologist, Tristram ClinicDiagnosing Dermatologist, MoleMap NZ
Case Studies in Psoriasis
12 June 2011
Tristram Clinic
Sponsored by Abbott
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Psoriasis
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What is psoriasis? A skin disease affecting ~3% of population Exaggerated proliferation of keratinocytes
Activated immune system Mediated by TNFα, IL23
An inherited disease most common in Caucasians Polygenic M=F; onset 20-39M, 40-59F
Many different diseases At least 10 different clinical types Early onset vs late onset
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What is psoriasis? A systemic disease Arthritis, metabolic syndrome: cardiovascular disease,
hypertension, dyslipidaemia, type 2 diabetes, renal disease
A lifestyle disease Aggravated by obesity, alcohol, smoking, stress
Especially if: Large plaques Early onset Severe
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Clinical characteristics of psoriasis Raised, well-defined erythematous plaques with irregular
borders and silvery scales Predilection for scalp, elbows, knees and trunk Very high negative impact of quality of life Requires long-term treatment Associated with decreased life span
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Psoriasis
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Molecular genetics: complicated1! Genetic variations studied by PCR & microarrays: Single nucleotide polymorphisms (SNPs) Copy number variants (CNVs) Copy-neutral loss of heterozygosity (LOH)
Psoriasis-susceptiblity loci PSORS 1-9 Some loci also code for metabolic syndrome, cardiovascular
disease, type 2 diabetes, familial hyperlipidaemia Gene expression data analysis Psoriasis is chronic interferon- and T-cell-mediated immune
disease of the skin where imbalance in epidermal cellular structure, growth and differentiation arises from molecular antiviral stress signals initiating inappropriate immune responses
1Al Robaee A A, Molecular genetics of Psoriasis. Int J Health Sci (Qassim) 2010;4:103-127
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Psoriasis is a systemic disease
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Immunopathogenesis: complicated1! Activated by environmental factors Mechanical trauma, infections, medications, emotional stress Release of IL1, TNFα, heat shock proteins
Stimulates innate immunity Dendritic cells in epidermis & dermis, keratinocytes Release chemokines, cytokines, growth factors
DC processes antigen (?what) triggering adaptive immunity Th1 cells produce INF-γ, TNF-α & IL-2 Th17 cells produce IL-17, TNF-α, IL-6 & IL-22 Tc1 cells produce TNF-α, INF-γ, perforins & granzyme B
1Sanchez APG. Immunopathogenesis of psoriasis. An. Bras. Dermatol. 2010; 85: no.5
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Immunopathogenesis: complicated1! Activated T-cells migrate to the epidermis & dermis Produce numerous cytokines, chemokines, antimicrobial peptides
Activated dendritic cells Produce more cytokines: IL12, IL 23 amplifying Th1 and Th17 response IL20, IL22 stimulates keratinocytes to proliferate IL17 stimulates keratinocytes to produce antimicrobial peptides TNF-γ stimulates keratinocytes to produce IL-8, IP-10, IL-1, TNF-α and
growth factors favouring angiogenesis Nitric oxide (iNOS) causes vasodilatation
Involves toll-like receptors Etc.
1Sanchez APG. Immunopathogenesis of psoriasis. An. Bras. Dermatol. 2010; 85: no.5
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Why do we have to know about this? Partly the same pathway as pathogenesis of atherosclerosis Patients with psoriasis have higher incidence of cardiovascular
diseases and metabolic syndrome
Biologic medications have immunological targets Anti T-cell (not so effective: e.g. alefacept) Anti TNF-α (adalimumab, etanercept, infliximab, golimumab) Anti IL12/23 (ustekinumab, briakinumab [in Phase III trials])
Compared to conventional treatments, they are more effective, safer and more convenient. They also may reduce mortality from comorbidities.
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Garcia-Valladares I et al. Drug Des Devel Ther. 2011; 5: 41–49.
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Psoriasis: phenotypic classification1
Localised Plaque psoriasis Limbs Trunk
Facial psoriasis Flexural psoriasis Scalp psoriasis Palmoplantar psoriasis
Widespread Guttate psoriasis Generalised pustular Erythrodermic psoriasis
Consider also: Stable/unstable Small/large plaque Onset <40 yrs />40 yrs ±Nail involvement Follicular
1Griffiths CE et al. A classification of psoriasis vulgaris according to phenotype. Br J Dermatol. 2007 Feb;156(2):258
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First, assess the patient Type, extent, severity and distribution of psoriasis Age, sex, occupation, domicile of patient Comorbidities, medications, adverse reactions Skin type, photosensitivity
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Case 1 – localised plaque psoriasis 48 year-old female Psoriasis for 4 years Confined to elbows, knees
and buttocks Complains of mild itch and
significant embarrassment
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Case 1 – topical options Topicals are suitable for
every patient The only treatment required
by those with mild psoriasis But not very effective and
sometimes difficult to apply
Emollients Keratolytics Topical steroids Vitamin-D derivatives Coal tar Dithranol
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Emollients Reduce: Itch Stinging Dryness
Choose: Lotion Cream Ointment
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Keratolytics Urea 10% cream Salicylic acid Lactic acid
In: Cetomacrogol cream Paraffin
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Potent topical steroid ointments Suitable for trunk, limbs Unsuitable for flexures Ineffective on palms/soles
Courses of 2-4 weeksThen: Weekend pulses
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Vitamin D derivatives Calcipotriol Daivonex® Ointment > Cream >
Solution Max. 100 g/week May irritate and peel Erythema tends to persist
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Coal tar
Messy & smelly Especially for scalp
(leave-ons & shampoos) Wash off after an hour or
more Refined coal tar less messy but
less effective than crude coal tar (LPC 2-20%)
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Dithranol Stains & burns Short-contact Suitable for large plaques
only
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Case 2 – Facial psoriasis 8 year-old boy Psoriasis for 6 months Facial psoriasis concerns
parents
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Case 2 – tx topical steroid
Clobetasone butyrate suitable for face, flexures
Ineffective elsewhere
Courses of 2-4 weeksThen: Weekend pulses
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Option for thin skin: calcineurin inhibitor
Pimecrolimus cream Elidel®
For face & flexural psoriasis
Children & adults Twice daily, longterm May burn at first
©R Suhonen (with permission)
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Case 3 – flexural psoriasis
60 year-old moderately obese woman
Chronic intertrigo: under breasts, abdominal folds, natal cleft, umbilicus
Embarrassing & painful during mammogram
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Case 3 – topical tx for moist skin folds
Calcipotriol cream bd If itchy, use qd
hydrocortisone cream Use potent topical steroids
sparingly e.g. for 2 weeks prior to mammogram
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Case 4 – scalp psoriasis 25 year-old woman Complained of itch, scale
and patchy hair loss Shampooing daily without
improvement
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Case 4 – shampoo options
One-month trial of ketoconazole shampoo
If ineffective, recommend tar shampoo
May add conditioner of choice
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Case 4 – to lift adherent scale
Soften scale with salicylic acid and tar prior to shampooing - try Coco Scalp cream
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Case 4 – to teach red patches
Add topical steroid solution or lotion two or three times weekly
If plaques thin, add calcipotriol solution bd
Do not let solution drip onto facial skin
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Antifungals
Malassezia yeasts provoke sebopsoriasis
Scalp, face, chest, groin Ketoconazole &
ciclopirox shampoo & cream
Trial of oral itraconazole for severe scalp psoriasis
©R Suhonen (with permission)
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Case 5 – acute guttate psoriasis
17 year-old presents with numerous small plaques
2 weeks prior to onset, acute streptococcal tonsillitis treated with penicillin
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Cace 5 – topical tx for psoriasis
Small plaques: emollients Itching: hydrocortisone
cream
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Case 5 - referred for phototherapy
Moderate to severe thin plaque psoriasis on trunk and limbs
Patient must live nearby & has transport
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Contraindications for phototherapy
Skin type 1 Photosensitivity Skin cancer: melanoma Inaccessibility
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Phototherapy for thin plaque psoriasis
Sunlight UVB Broadband Narrowband - 311nm Targeted
PUVA Whole body (outmoded) Localised
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Phototherapy regime 3 times weekly, 6-12 weeks Protect genitals & face Aim for pink skin (not red) Increase dose progressively
Pre UVB
Post UVB
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Complications of phototherapy
Burns Photosensitive rashes Photoaging Skin cancer
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Case 6 – keratoderma of palms & soles
New onset plaques on both palms
Longstanding scaly feet Fissuring – painful to walk Unsightly nail dystrophy Resistant to topical therapy
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Case 6 – topical tx for keratoderma
Keratolytic emollients to descale e.g., salicylic acid ointment
Use ultrapotent topical steroid bd for 4 weeks then 2 or 3 times per week, if necessary under occlusion
Coal tar ointment is messy -may help soles
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Case 6 – localised phototherapy
Hands & feet can be treated by bathwater PUVA soaks
Three times weekly for ≥3 months
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Case 7 – palmoplantar pustulosis 58 year-old smoker Itchy, painful, unsightly
Palmoplantar pustulosis is no longer considered Psoriasis
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Case 7 – options for pustulosis Crude coal tar effective but
no longer available Limited benefit from: Emollients Refined coal tar ointment Ultrapotent topical steroid
Doxycycline 100mg x 3 mth Refer for phototherapy +
acitretin
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Case 6 & 7 – acitretin: Neotigason®
Special authority application
10 - 50 mg daily Emollients
Contraindication: Pregnancy Childbearing potential Untreated hyperlipidaemia
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Monitoring acitretin
CBC, LFT, lipids Monthly x 3 3-monthly
Review patient regularly for efficacy and to manage mucocutaneous side effects
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Adverse reactions to acitretin
Teratogen Mucocutaneous dryness Retinoid dermatitis Staph. aureus infection
Cheilitis Paronychia
Tiredness Hypertrygliceridaemia Hepatitis (rare)
It can make your hair curl!
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Case 8 – chronic plaque psoriasis 45 year-old woman with
longstanding plaque psoriasis
Nail dystrophy Painful swollen finger
joints Heavy smoker Recently flare
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Case 8 – assessment of psoriasis BSA 15% PASI score 20 DLQI score 20
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Assessment: PASI score (0-70)
http://pasi.corti.li/
http://www.dermnetnz.org/scaly/pasi.html
If PASI>10, psoriasis is severeIf BSA>10, psoriasis is severe
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Assessment: DLQI (score 0-30)
If DLQI >10, psoriasis has significant impact
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Case 8 – nail dystrophy Pitting, onycholysis,
ridging, subungual hyperkeratosis, nail thickening or splitting
May resemble onychomycosis – if in doubt, obtain clippings for mycology
Treatment-resistant Associated with psoriatic
arthritis affecting digits
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Case 8 – psoriatic arthritis? PsA affects ~30% who have psoriasis 70% skin first 15% joints first 15% skin with joints Often nails / distal fingers
Presents with: PIP, DIP synovitis Dactylitis (sausage finger) Enthesitis (heel, plantar) Oligoarthritis large joints Spinal involvement
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Psoriatic arthritis assessment Screening questionnaire E.g. PASE 7 Q symptoms, 8 Q function PASE >47 = high risk
Refer if: Morning stiffness >2 hr Nail disease Pain a.m. > p.m. Swelling / dactylitis Enthesitis
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Case 8 – consider exacerbating factors?
Infection – bacterial, viral Injuries including sunburn Psychological stress Smoking Metabolic syndrome Drugs: lithium, interferon, ?antimalarials, ?beta blockers etc
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Case 8 – co-morbidities? Abdominal obesity Type 2 diabetes Low HDL cholesterol High triglycerides High blood pressure Coronary heart disease
Metabolic syndrome leads to psoriasis that is: Extensive Resistant to treatment Release of TNFα Abdominal fat releases
growth factors Phototherapy burns,
ineffective
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Benefits of weight loss Lowered blood pressure Reduced total cholesterol and improved LDL/HDL
cholesterol ratio Lowered triglyceride levels Improved insulin sensitivity Reduced extent & severity of psoriasis
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Case 8 - topical tx for trunk & limbs Large plaques: calcipotriol ointment twice daily Potent or ultrapotent topical steroid ointment (e.g.,
Dermol®, Elocon®) as weekend pulses) Extensive psoriasis unlikely to clear with topical therapy Poorly motivated to treat extensive areas long term
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Risks from ultrapotent steroids
Cushing’s if applied to large areas for long periods
Localised skin atrophy Monitor prescriptions Use intermittently 2 days per week
Examine the patient
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Treat arthritis before it’s mutilating NSAID symptoms only MTX Sulfasalazine Lefluomide TNFα inhibitor Etanercept Adalimumab Infliximab Golimumab
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Case 8 – oral treatment options
Metformin for metabolic syndrome & for psoriasis
Methotrexate: helps PsA Acitretin Ciclosporin
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Case 8 – methotrexate
15 mg once weekly ?Folic acid 2 days/week Slowly effective over 3 months
Pretreatment checks: No liver disease Minimal EtOH Using contraceptives
(M + F) Not on other folate antagonists
e.g. trimethoprim
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Monitoring methotrexate
CBC, LFT, Renal Weekly x 4 Monthly x 3 3-monthly
P3NP collagen Baseline + 6-monthly
Transient elastography Baseline + 3-yearly
Liver biopsy If abnormal
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Adverse reactions to methotrexate
GI disturbance Mouth ulceration Hepatitis Hepatic fibrosis &
cirrhosis
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Case 9 – severe resistant psoriasis A 56 year old farmer with
psoriasis since his 20s. Non-smoker, moderate alcohol. Psoriatic arthritis hands & feet. Past melanoma – unsuitable for
phototherapy Acitretin, ciclosporin unhelpful
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Case 9 – other options Ciclosporin Hydroxyurea Azathioprine 6-mercaptopurine Mycophenolate Biologic agents
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Case 9 – ciclosporin: Neoral®
2.5 - 5 mg/kg/day until clear Drug interactions ++ Motivated patients:
Severe psoriasis Failed to clear with other meds Adverse effects from other meds
Works quickly for most patients
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Contraindications to ciclosporin
Renal dysfunction Uncontrolled
hypertension Skin cancers Non-compliant patient
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Monitoring ciclosporin
Creatinine 2-weekly x 8 weeks Monthly
BP 2-weekly x 8 weeks Monthly Treat if increased (or dose
reduction)
LFT, uric acid, lipids 3-monthly
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Adverse effects from ciclosporin
Hypertension Renal dysfunction Skin cancer
GI disturbance Paraesthesias, tremors Hirsutism
Dependence
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Other options – hydroxyurea 500 - 1000 mg daily Monitor CBC Macrocytosis Leucopaenia
Slow to be effective Can induce leg ulcers and
skin cancers
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Azathioprine and 5-mercaptopurine Rarely used for psoriasis as not
very effective Pretreatment assessment
thiopurine methyltransferase 50 to 150 mg daily Monitor CBC, LFT every 2
weeks for 8 weeks then monthly
Complications Pancytopaenia Hepatitis Risk of skin cancer, lymphoma
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Mycophenolate: Cellcept® Now on Special Authority
to dermatologists for treatment-resistant skin disease including psoriasis
Contraindications: Pregnancy
1 to 1.5 g twice daily Complicatons: Anaemia GI tract symptoms Infections
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Case 9 – assessment Failed ciclosporin PASI 20 on methotrexate DLQI 15 Grade 2-3 hepatic steatosis,
psoriatic arthritis, meniere’s, hypertension
Negative tests for TB, hepatitis viral serology
Considered for biologic treatment
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Case 9 - adalimumab: Humira® Special Authority application
if PASI ≥15 on treatment and failed phototherapy, mtx, acitretin, ciclosporin
TNFα blocker Workup includes: TB: CXR, Mantoux,
quantiferon Gold Hepatitis B, C, HIV
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Case 9 at 3 months• Adalimumab 80mg sc
stat, 40mg after one week then 40mg every 2 weeks
• PASI 3, DLQI 0
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Case 10 – Longstanding severe psoriasis with exanthematic flares A 58 year-old early
childhood teacher. Non-smoker, moderate
alcohol. Obesity, type 2 diabetes,
hypertension, depresson. Failed treatment included:
acitretin, methotrexate, ciclosporin, UVB
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Case 10 – work up for adalimumab 95kg PASI = 16 DLQI = 10 PASE = 57 Negative tests for TB,
hepatitis viral serology
Treated with adalulimab PASI = 3 at 3 months
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Case 10 – tx with adalimumab PASI = 3 at 3 months DLQI = 0 PASE = 57
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Case 10 – relapse On adalimumab for 6 months PASI = 10 PASE = 57 Unhappy patient!
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Case 10 – tx with etanercept Etanercept 50mg twice
weekly for 3 months, expecting to reduce to once weekly in July 2011
At 2 months, verbal report is that psoriasis is nearly clear
Adverse effects: bronchitis and superficial skin infection
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Etanercept: Enbrel® Special Authority application
if PASI ≥15 on treatment and failed phototherapy, mtx, acitretin, ciclosporin
TNFα blocker Workup includes: TB: CXR, Mantoux,
quantiferon Gold Hepatitis B, C, HIV
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Biologic agents for severe psoriasis TNF blockers: Infliximab IV infusion Adalimumab SC every 2 wks Etanercept SC every week
Anti-IL 12/23: Ustekinumab every 3
months (unfunded)
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Advantages of biologic agents Very effective PASI 75 in 60% at 3-6
months Well tolerated Very happy patients!
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Disadvantages of biologic agents
Expensive Increase infection Treat aggressively Monitor for TB
May increase risk of lymphoma (rare)
Relapse may occur They can cause skin
rashes including psoriasis!
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For further information: