PSORIASIS

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PSORIASIS
Andrew Blauvelt, M.D.Professor, Dept. of
Dermatology and Dept. of Molecular Microbiology
ImmunologyOregon Health Science
UniversityChief, Dermatology Service Veterans
Affairs Medical CenterPortland, Oregon
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CONFLICTS OF INTEREST
Centocor scientific advisor, investigator
for clinical studies, received lab research
funds Abbott scientific advisor,
investigator for clinical studies Lilly
scientific advisor, investigator for clinical
studies Amgen scientific advisor
Novartis scientific advisor
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WHAT IS PSORIASIS?

• A common, life-long, genetic, autoimmune skin
  disease
• Characterized by well circumscribed areas of
  thick, red, scaly skin
• From the Greek psoros meaning rough, scabby
• Term first used (along with lepra) by
  Hippocrates (460-377 B.C.) in Corpus
  Hippocraticum
• von Hebra first to distinguish psoriasis from
  leprosy in 1841

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• Under the microscope, affected skin is thickened,
  has increased blood vessels, and contains
  numerous white blood cells

• Affected skin is painful, itchy, often bleeds,
  and is debilitating when involving the face,
  genitals, palms, or soles

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CLASSIC ANATOMIC LOCATIONS FOR PSORIASIS

• Scalp (80)
• Elbows (78)
• Legs (74)
• Knees (57)
• Nails (10-55)
• Gluteal cleft
• Palms/soles (12)

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CLINICAL VARIANTS

• Chronic plaque psoriasis
• Guttate psoriasis
• Erythrodermic psoriasis
• Generalized pustular psoriasis (von Zumbusch)
• Localized pustular psoriasis
• Palmaris et plantaris
• Acrodermatitis continua
• Inverse psoriasis

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PSORIATIC NAIL CHANGES

• Onycholysis
• Oil drops
• Salmon patches
• Pitting
• Subungual debris
• Onychodystrophy
• Splinter hemorrhages

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TRIGGERS FOR PSORIASIS

• Direct skin injury (Koebner phenomenon)
• Discontinuation of systemic corticosteroids
• Cold weather
• Streptococcal pharyngitis
• Emotional stress
• Alcohol intake
• Smoking
• HIV
• Medications

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DRUGS THAT CAN EXACERBATE PSORIASIS

• Beta blockers
• Lithium
• IFN-alpha
• Antimalarials
• ACE inhibitors
• Rebound with withdraw of prednisone and
  cyclosporine

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TYPICAL HISTORY FOR PSORIASIS

• Average age of onset is 28 years, although
  disease can begin in infants or in the elderly
• Bimodal peaks late teens (type I psoriasis,
  family history) and early 40s (type II
  psoriasis, no family history)
• Once it has begun, it persists
• Many patients have family members affected,
  although many others do not
• At least 10 genes identified HLA-Cw6, IL-23 p19,
  IL-12/IL-23 p40, IL-23R

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PSORIASIS IS NOT JUST A SKIN DISEASE

• Psoriatic arthritis occurs in approximately 30
  of patients with psoriasis
• Depression and alcohol abuse are common in
  individuals with psoriasis
• Obesity tends to make psoriasis worse, and
  psoriasis tends to make obesity worse
• Severe psoriasis is associated with up to a 7X
  risk for developing myocardial infarction,
  especially at a younger age
• Severe psoriasis is associated with increased
  mortality (5 year shorter life span)

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PSORIASIS SIGNIFICANTLY IMPAIRS QUALITY OF LIFE

• Fear of contagion from others (modern day
  lepers)
• Low self esteem (somethings wrong with me)
• Need to cover up (I dont want anyone to see)
• Sexual impairment
• Hand/foot lesions that interfere with activities
  of daily living
• Itching that interferes with sleep and activities
  of daily living
• Arthritis that impairs activities of daily living

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PSORIASIS AS A SYSTEMIC DISEASE CHANGING PRACTICE

• Use systemic therapy more (do TNF-? blockers have
  beneficial effects on metabolic
  syndrome/cardiovascular risk/mortality?)
• More monitoring baseline blood pressure, fasting
  glucose/lipids
• More conversations on smoking and alcohol
  cessation
• More referrals to internal medicine, nutrition,
  cardiology, rheumatology, psychiatry, gastric
  bypass surgery

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SEVERITY OF PSORIASIS(older view)

• Mild disease lt5 of body surface covered (65 of
  patients with this type)
• Moderate disease 5-10 of body surface area
  covered (25 of patients with this type)
• Severe disease gt10 of body surface area covered
  or palm/sole involvement (10 of patients with
  this type)

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SEVERITY OF PSORIASIS(contemporary view)

• Mild, moderate, and severe replaced with
• Candidates for localized therapy
• Candidates for systemic therapy
• Candidates for systemic therapy may have one or
  more of the following features
• BSA greater than 5
• Involvement of vulnerable areas of the body,
  including palms, soles, face, scalp, and genitals
• Significant impact on quality of life
• Failure of localized therapy
• Concomitant psoriatic arthritis

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TOPICAL THERAPIES FOR PSORIASIS

• Corticosteroids mid-high potency for most areas,
  low potency for face and intertriginous areas
• Calcipotriene (Dovonex) works best in
  combination with topical corticosteroids
• Tazorotene (Tazorac) works best in combination
  with topical corticosteroids
• Tacrolimus (Protopic) for face and
  intertriginous areas
• Ointments, creams, gels, foams, sprays, shampoos,
  and medicated tape all available

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OLDER SYSTEMIC THERAPIES FOR PSORIASIS

• Phototherapy UVB, narrow-band UVB, PUVA, Excimer
  laser
• Methotrexate
• Acitretin (Soriatane)
• Cyclosporine

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BIOLOGIC TREAMENTS FOR PSORIASIS/PSORIATIC
ARTHRITIS

• Alefacept (Amevive) LFA3-tip, targets CD2 T
  cells
• Etanercept (Enbrel) soluble TNF-? receptor
• Adalimumab (Humira) human anti-TNF-? mAb
• Infliximab (Remicade) chimeric anti-TNF-? mAb
• Golimumab (Simponi) human anti-TNF-? mAb
• Ustekinumab (Stelara) human anti-IL-12/IL-23 mAb

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APPROXIMATE PASI 75 RESPONSES TO BIOLOGICS AT
WEEK 12

• Alefacept (Amevive) 20-25
• Etanercept (Enbrel) 40-50
• Adalimumab (Humira) 60-70
• Infliximab (Remicade) 75-80
• Golimumab (Simponi) 50
• Ustekinumab (Stelara) 70 (80 at week 24)

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MAJOR POTENTIAL SIDE EFFECTS OF TNF-? BLOCKING
AGENTS

• Infection (3x), including hepatitis B
• and TB reactivation
• Lymphoma (rare, 3x in RA)
• Multiple sclerosis (rare)
• Worsening of CHF
• Transaminitis (infliximab gt others)
• Cytopenias (rare)

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MONITORING BEFORE AND DURING METHOTREXATE AND
TNF-? BLOCKER USE

• Baseline PPD, hepatitis profile, CBC with diff,
  chemistry panel
• Every 3 months clinically monitor progress and
  perform ROS for tolerability, infections, cancers
  (lymphoma), MS CBC with diff and chemistry panel
  for methotrexate
• Every 6 months CBC with diff and chemistry panel
  for TNF-? blockers
• Every year PPD for TNF-? blockers

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PRACTICAL FACTORS INVOLVED IN CHOOSING SYSTEMIC
THERAPY

• Efficacy (PASI 75)
• Potential side effects of drug
• Type of psoriasis
• Impact on quality of life/patient needs
• Presence/absence of psoriatic arthritis
• Concomitant morbidities
• Ease of administration
• Insurance coverage/out of pocket costs
• FDA approved for indication

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BLAUVELT PREFERENCES IN CERTAIN SETTINGS

• Moderate-to-severe psoriasis methotrexate first,
  then TNF-? blocker (NB-UVB if practical)
• Psoriatic arthritis with any amount of skin
  disease methotrexate first, then adalimumab
• Moderate-to-severe skin disease and concomitant
  alcohol abuse/hepatitis C etanercept, adalimumab
• Moderate-to-severe skin disease and concomitant
  obesity/diabetes/metabolic syndrome adalimumab
• Palmoplantar disease methotrexate, acitretin
• Erythrodermic psoriasis infliximab
• Pustular psoriasis infliximab, acitretin
• HIV psoriatic acitretin, NB-UVB if practical

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NATIONAL PSORIASIS FOUNDATION (NPF)

• Established as patient support group in Portland,
  OR in 1968
• The best information about psoriasis, psoriatic
  arthritis, and treatments
• Psoriasis Advance magazine, 6 issues per year
• Support and encouragement through an online
  community of thousands
• Directory of doctors
• Assistance on insurance issues
• Driving research for better treatments and
  control
• Encourage all of your patients to join

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THE END