II. Epidemiology

  1. Bimodal peaks for Plaque Psoriasis
    1. Young adulthood (ages 16 to 22 years old)
    2. Older age (late 50s)
  2. Prevalence: 1-3% of general population (U.S.)
  3. Men and women affected equally

III. Pathophysiology

  1. Underlying genetic predisposition is common
    1. Pathogenesis is likely a combination between genetic predisposition and exposure to inciting triggers
    2. Of those with Psoriasis, 30% also have a first degree relative with Psoriasis
    3. Children have a 50% chance of Psoriasis if both parents have Psoriasis (16% if only one parent has Psoriasis)
    4. Diabetes Mellitus Type 2 genetic predisposition also have higher Psoriasis risk (shared genetic loci)
  2. Autoimmune
    1. Viral Infection may precipitate process
    2. T-Cell-mediated autoimmune response
      1. Cytokines released and stimulate Keratinocytes
  3. Keratinocytes proliferate
    1. Epidermal cells proliferate too fast
      1. Cells cycle in 4 days instead of normal 3-4 weeks
    2. Abnormal keratin production
    3. Dermal inflammation

IV. Risk Factors: Environmental Factors

  1. Suppressed by:
    1. Sun and humidity
  2. Provocative
    1. Injury to skin (e.g. Tattoo)
      1. Koebner Reaction with Plaque formation within 10 to 20 days of Skin Injury
    2. Lifestyle
      1. Emotional upset
      2. Tobacco Use
      3. Obesity
      4. Glucose Intolerance or Metabolic Syndrome
      5. Alcohol Abuse
    3. Infections
      1. Streptococcal Pharyngitis
      2. HIV Infection (severe exacerbations)
    4. Medications
      1. ACE Inhibitors
      2. Antimalarials
      3. Beta Blockers (e.g. Propranolol)
      4. Lithium
      5. NSAIDS

V. Symptoms

  1. Pruritus is present in >80% of psorisis
    1. Psora is greek for itching

VI. Signs: Chronic Plaque Psoriasis (90% of adult cases)

  1. Description
    1. Widespread
    2. Sharply demarcated
    3. Bright pink, red or salmon-colored Plaques
      1. Violet, red or blue coloration on darker skin
    4. Overlying loose, white to silvery scale
  2. Location: Symmetrical
    1. Over joints and extensor surfaces of extremities
    2. On trunk, especially lower back and buttocks
    3. Palms and soles
    4. Scalp
    5. Umbilicus
  3. Signs suggestive of Psoriasis
    1. Auspitz Sign
    2. Koebner Phenomenon

VII. Signs: Psoriatic Variants (Less Common)

  1. Guttate Psoriasis (drop-like)
    1. Uncommon, accounting for only 2% of Psoriasis cases
    2. Typically affects younger patients, under age 30 years, and especially school age children
    3. Trunk lesions are 3-5 mm (range 1-10 mm) Papules with fine scale
    4. Commonly occurs 2-4 weeks following Streptococcal Pharyngitis (esp. in children)
      1. When associated with Streptococcal Pharyngitis, 60% will have complete remission within months
      2. When not associated with Streptococcal Pharyngitis, risk of progression to plaque Psoriasis
    5. Other infectious disease associations
      1. Upper Respiratory Infection
      2. Staphylococcus aureus
      3. Helicobacter Pylori
      4. Borrelia Burgdorferi (Lyme Disease)
      5. Viruses (e.g. Covid19, HIV, HPV, VZV, Hep B, Hep C, EBV)
  2. Inverse Psoriasis (flexural)
    1. Well demarcated erythematous lesions with minimal scale affecting the skin folds
    2. Less scale present than in Plaque form
    3. Affects flexor surfaces (inframammary, axillary and inguinal folds)
    4. Affects perineal and intergluteal regions
  3. Palmoplantar Pustulosis (Pustular Psoriasis)
    1. Likely represents a distinct condition from Psoriasis
    2. Multiple pin-sized, sterile Pustules on red base on the palms and soles without Plaques
    3. Most commonly triggered by medications that have been recently started (86% of cases)
      1. Penicillins
      2. Macrolides
      3. Quinolones
      4. Sulfonamides
      5. Terbinafine
      6. Diltiazem
    4. Acute Generalized Exanthematous Pustulosis (von Zumbusch) variant
      1. Severe, acute, life-threatening sub-type develops in <2 weeks
      2. Biopsy intact Pustule to exclude
  4. Erythrodermic Psoriasis (Erythroderma)
    1. Broad-spread generalized erythema and Desquamation involving >75% of body surface area (BSA)
    2. Systemic symptoms are typically present (see below)
    3. Acute, Type 2 form may be life threatening (in contrast to the chronic, Type 1 form)

VIII. Signs: Associated Findings

  1. Nail Psoriasis (Psoriatic Onychodystrophy)
    1. Lifetime Prevalence in up to 90% of Psoriasis patients (esp. Fingernails)
    2. Associated with higher risk of Psoriatic Arthritis
    3. Findings secondary to abnormal nail plate growth
      1. Nail Pitting
      2. Subungual hyperkeratosis
      3. Onycholysis
        1. Separation of distal edge of nail from nail bed
        2. Accumulation of crumbly subungual debris
  2. Other location specific signs
    1. Gluteal cleft
      1. Eroded pinkness in crease
    2. Penis (genital involvement in 40% of cases)
      1. Pink Macules or Plaques on penis
    3. Large joints
      1. Hyperkeratosis over elbows, knees, and ankles
    4. Tongue
      1. Geographic Tongue (rare)
  3. Systemic Signs
    1. Psoriatic Arthritis
    2. Uveitis (up to 20% of Psoriatic Arthritis cases)
  4. Severe widespread Psoriasis systemic signs
    1. Benign Lymphadenopathy
    2. Fever, chills, and Hyperthermia
    3. Increased cardiac demand
    4. High output Heart Failure
    5. Increased Sedimentation Rate and Uric Acid
    6. Decreased Serum Albumin
    7. Iron Deficiency Anemia

IX. Grading: Severity

  1. Involved Body Surface Area (BSA)
    1. er_burn_ruleOf9_adult.png
    2. Mild: <3% BSA
    3. Moderate: 3 to 10% BSA
    4. Severe: >10% BSA
  2. Psoriasis Area and Severity Index (PASI)
    1. https://www.mdcalc.com/calc/10182/psoriasis-area-severity-index-pasi
    2. Mild: PASI<5
    3. Moderate: PASI 5 to 10
    4. Severe: PASI>10
  3. Life Quality Indexes (LQI)
    1. Children's Dermatology Life Quality Index (CDLQI)
    2. Dermatology Life Quality Index (DLQI)
    3. Mild: LQI <5
    4. Moderate: LQI 5 to 10
    5. Severe: LQI >10

X. Differential Diagnosis

  1. Plaque Psoriasis
    1. Lichen Simplex Chronicus
    2. Nummular Eczema
      1. Eczema lacks overlying scale and typically affects the flexor surface
    3. Seborrheic Dermatitis
    4. Tinea Corporis
      1. Ring-like lesion with central clearing
    5. Cutaneous Squamous Cell Carcinoma
      1. Sun exposed areas
    6. Group A Beta Hemolytic Streptococcus
      1. May present as Guttate Psoriasis in children
      2. Obtain ASO Titer and Throat Culture
  2. Guttate Psoriasis
    1. Pityriasis Rosea
      1. Smaller lesions that follow skin Cleavage Lines, and develop after viral illness
    2. Secondary Syphilis
      1. Erythematous Papules also involve palms and soles (spared in Psoriasis)
  3. Erythrodermic Psoriasis (Erythroderma)
    1. Atopic Dermatitis
    2. Fixed Drug Eruption
    3. Toxic Epidermal Necrolysis
    4. Cutaneous Sarcoidosis
    5. Pityriasis rubra pilaris
  4. Palmoplantar Pustulosis (Pustular Psoriasis)
    1. See Palmoplantar Pustulosis
  5. Inverse Psoriasis (flexural)
    1. See Intertrigo
  6. Nail Psoriasis (Psoriatic Onychodystrophy)
    1. See Nail Pitting
    2. See Onycholysis
    3. Onychomycosis

XI. Associated Conditions (some related to psoriatic medications)

  1. Psoriatic Arthritis
    1. Affects 30% of adult plaque Psoriasis patients
      1. Children develop Psoriatic Arthritis in ~1% of Psoriasis cases
    2. Median onset 10 to 11 years after skin lesion onset in adults
      1. Up to 20% may have Psoriatic Arthritis findings that precede skin lesions
  2. Inflammatory Bowel Disease (Crohns' Disease or Ulcerative Colitis)
    1. Risk increased 3.8 to 7.5x
  3. Celiac Disease (in 4-14% of Psoriasis patients)
  4. Malignancy
    1. Colorectal Cancer
    2. Squamous Cell Skin Cancer
      1. Risk increased 14x associated with PUVA in caucasians
    3. Lymphoma
      1. Risk increased 1.3 to 3x
  5. Major Depression
    1. Prevalence: 60% of Psoriasis patients
    2. Also associated with Anxiety Disorder and Suicidality
  6. Other associated conditions with increased risk
    1. Myocardial Infarction
    2. Atrial Fibrillation
    3. Metabolic Syndrome

XII. Management: General Measures

  1. Skin Emollients
    1. Soak lesions to ease adherent scale removal
    2. Apply Lac-Hydrin or salicylic acid applied daily to Plaques (reduces Scaling and softens Plaques)
    3. Apply skin Emollients (e.g. vaseline, aquaphor)
      1. Apply after soaks
      2. Apply 20 minutes after Corticosteroid application to boost steroid effect (similar to Occlusion)
      3. Consider Emollient only periods of steroid holiday
  2. Other lifestyle measures
    1. Maintain Ideal Body Weight
    2. Avoid Tobacco
    3. Limit Alcohol
    4. Stress Reduction
  3. Dermatology Referral Indications
    1. Psoriasis not responsive to topical agents
    2. Psoriasis diagnosis unclear
    3. Severe Psoriasis
    4. Refractory Guttate Psoriasis (requiring UVB Therapy)
    5. Moderate to severe nail Psoriasis requiring systemic therapy
  4. Other specialty referral indications
    1. Psoriatic Arthritis (Rheumatology)
    2. Inflammatory Bowel Disease (Gastroenterology)

XIII. Management: Approach - Mild Chronic Plaque Psoriasis

  1. See General Measures above
  2. Indications: Mild Chronic Plaque Psoriasis
    1. Involved Body Surface Area (BSA) <3%
    2. Psoriasis Area and Severity Index (PASI) <5
    3. Life Quality Index (LQI) <5
  3. Intermittent Flares
    1. Low potency Topical Steroids: Thin Skin (Skin folds, face, genitalia)
    2. High potency Topical Steroids: Thick Skin (Palms, soles, scalp, nails)
  4. Maintenance (Corticosteroid sparing agents)
    1. Vitamin D based topicals (Calcipotriene, Calcitriol)
    2. Calcineurin Inhibitor (Tacrolimus, Pimecrolimus)
    3. Topical Retinoids (Tazarotene)

XIV. Management: Approach - Moderate Chronic Plaque Psoriasis

  1. Indications: Moderate Chronic Plaque Psoriasis
    1. Involved Body Surface Area (BSA) 3 to 10%
    2. Psoriasis Area and Severity Index (PASI) 5 to 10
    3. Life Quality Index (LQI) 5 to 10
  2. Trunk and extensor surface involvement
    1. Initial and exacerbation therapy (<4 weeks only)
      1. Protocol 1: Topical Steroid and Calcipotriene
        1. High potency Topical Corticosteroid qAM and Calcipotriene qPM or
        2. High potency Topical Corticosteroid and Calcipotriene mixed 1:1 and applied daily or
        3. High potency Topical Corticosteroid daily weekends and Calcipotriene daily weekdays
      2. Protocol 2: Single agent
        1. High potency Topical Corticosteroid or
        2. Calcipotriene or
        3. Tazorotene (Tazorac)
    2. Long-term maintenance (beyond 4 weeks)
      1. Calcipotriene or
      2. Tazorotene (Tazorac)
  3. Flexor surface involvement
    1. Moderate Topical Corticosteroids (<4 weeks) OR
    2. Calcineurin Inhibitor (Tacrolimus or Pimecrolimus)
  4. Scalp involvement
    1. Exacerbations
      1. Calcipotriene/Betamethasone Dipropionate gel for 4 to 12 weeks (8 weeks in age 12 to 18 years) OR
      2. Calcipotriene foam for 4 to 12 weeks OR
      3. Clobetasol 0.05% Shampoo used briefly
    2. Maintenance
      1. Anti-DandruffShampoo (e.g. T-gel or selsun)
  5. Nail Involvement
    1. Exacerbations with 1-2 nails involved
      1. Calcipotriene/Betamethasone Dipropionate and Tazarotene
  6. Adjuncts
    1. Lac-Hydrin or salicylic acid applied daily to soften Plaques

XV. Management: Approach - Severe Chronic Plaque Psoriasis

  1. Indications
    1. Severe Chronic Plaque Psoriasis
      1. Involved Body Surface Area (BSA) >10%
      2. Psoriasis Area and Severity Index (PASI) >10
      3. Life Quality Index (LQI) >10
    2. Psoriasis refractory to topical and UVB therapy
    3. Comorbid Psoriatic Arthritis
    4. Involvement of hands, feet, face or genitalia
  2. Protocol usually managed by dermatology
    1. Use above topical agents
    2. See UVB Therapy as below
    3. Most effective Biologic Agents in severe Chronic Plaque Psoriasis
      1. See Systemic Agents below (non-biologics and biologics)
      2. Infliximab
      3. Bimekizumab
      4. Ixekizumab
      5. Sbidian (2023) Cochrane Dabatase Syst Rev (7): CD011535 [PubMed]

XVI. Managament: Approach - Children and Teens

  1. Presentations
    1. Plaque Psoriasis
      1. Typical onset in teens
    2. Guttate Psoriasis
      1. Onset in younger children, and frequently associated with Streptococcal Pharyngitis
      2. Spontaneous remission within months for 60% whose onset was associated with Strep Throat
    3. Psoriatic Arthritis
      1. Complicates only 1% of childhood Psoriasis (contrast with 30% comorbid Psoriatic Arthritis in adults)
      2. Younger children present with Oligoarthritis and Dactylitis
      3. Oldern children and teens present with enthesitis and axial joint involvement
    4. Complications (associated with Bullying, esp. teens)
      1. Major Depression
      2. Substance Abuse
  2. First-line agents
    1. Skin Emollients and keratin-softening agents (See general measures as above)
    2. Topical Corticosteroids (any age)
      1. Daily use in flares for up to 14 days
      2. Avoid high potency Corticosteroids (if possible) in age <6 years
    3. Calcipotriene (age >12 years)
      1. Use with or without Corticosteroids for up to 4 weeks
      2. See Vitamin D Analog Topicals below for precautions (esp. Hypercalcemia risk)
    4. Narrowband UVB Phototherapy
      1. Indicated in children with involved BSA 10 to 25%
      2. Consider in combination with coal tar pretreatment for 12 days
  3. Second-Line Agents in refractory, moderate to severe cases
    1. Methotrexate
    2. Biologics
      1. Etanercept (age >=4 years)
      2. Ustekinumab (age >= 6 years)
      3. Ixekizumab (age >= 6 years)
      4. Secukinumab (age >= 6 years)

XVII. Management: Approach - Pregnancy

  1. Most Psoriasis improves during pregnancy and worsens postpartum
    1. However, variable across pregnancies (and can worsen in up to a third of pregnancies)
    2. Topicals should not be applied near the nipple in lactating mothers (avoid infant ingesting medication)
  2. First-line
    1. Topical Skin Lubricants
    2. Low to moderate potency Topical Corticosteroids (<60 g/week in pregnancy)
    3. UVB Phototherapy
      1. UVB decreases Serum Folate
      2. Maintain at least 0.8 mg Folate daily
  3. Severe cases (after first trimester)
    1. TNF Inhibitors
      1. Stop early in third trimester
      2. Avoid Live Vaccines in newborns for first 6 months
    2. Interleukin-12/23 Inhibitors (e.g. Ustekinumab)
      1. Likely safe in pregnancy and Lactation
    3. Interleukin-17 Inhibitors (e.g. Secukinumab, Ixekizumab)
      1. Likely safe in pregnancy and Lactation
    4. Systemic Corticosteroids
    5. Cyclosporine
      1. May increase risk of Low Birth Weight Infant, premature birth, maternal infection
      2. Avoid in Lactation
  4. Contraindicated Agents in Pregnancy and Preconception
    1. Calcineurin Inhibitor (Tacrolimus, Pimecrolimus) if >1% BSA involved
    2. Retinoids (Acretretin, Tazarotene)
    3. Apremilast (based on animal studies)
      1. Men should also avoid for at least 2 days before conception
    4. Methotrexate
      1. Allow for at least 3 month washout before conception
  5. References
    1. Erlandson (2023) Am Fam Physician 107(2): 152-8 [PubMed]

XVIII. Management: Topical Preparations

  1. Skin Emollients and keratin-softening agents
    1. See general measures as above for protocols including soaking
    2. First-line agents for daily use
    3. Skin Emollients (e.g. vaseline, aquaphor)
      1. Applied daily
      2. See Skin Lubricant
    4. Keratin-softening agents
      1. Applied daily to Plaques (reduces Scaling and softens Plaques)
        1. Apply before Topical Corticosteroids or Calcineurin Inhibitors
      2. Lac-Hydrin (Alpha-Hydroxy acid)
      3. Salicylic acid (2 to 6%, Keratolytic Agent)
        1. Applied once daily (twice daily for thick Plaques)
        2. In age <6 years, limit to 0.5% and only to small patches
        3. Decreases UVB Phototherapy efficacy
        4. Inactivates Vitamin D Analogs (Calcipotriene, Calcitriol)
  2. Topical Corticosteroids
    1. High Potency Topical Steroids (Class 2 to 5, usually indicated for treatment, esp. on thicker skin)
      1. Dosing
        1. Very high potency: e.g. Clobetasol (Temovate)
        2. High potency: e.g. Fluocinonide (Lidex)
      2. Contraindications
        1. Thin skin (e.g. face, genitalia, Forearms)
        2. Avoid high potency Topical Corticosteroids in children age <6 years (if possible)
      3. Limit to 1 potent steroid applied up to twice daily for a maximum of 4 weeks (2 weeks in children)
        1. May extend to longer use on palms and soles
      4. Taper off potent steroids (over 2 weeks) to prevent rebound exacerbation
        1. Apply every other day for 1 week, then
        2. Apply twice weekly, then stop
      5. Maintenance
        1. Rotate to lower potency steroids or decrease application frequency (e.g. twice weekly)
        2. Consider Emollient only periods until reexacerbation
    2. Low to Medium Potency Topical Steroids (e.g. Hydrocortisone 2.5%)
      1. Face
      2. Genitalia
      3. Forearms
      4. Intertriginous regions
      5. Maintenance Therapy
  3. Intralesional Corticosteroids
    1. Indications
      1. Mild to moderate psoriatic Plaque on thick skin (e.g. scalp, palms, soles) not responding to topical agents
    2. Dosing
      1. Triamcinolone Acetonide 2.5 to 20 mg/ml injected into lesion every 3-4 weeks
  4. Vitamin D Analog Topicals (Calcipotriene, Calcitriol)
    1. Indications
      1. Moderate Psoriasis involving 5-20% of body surface area
      2. Mild to moderate scalp Psoriasis (foam or gel for 4-12 weeks)
      3. Alternative to Corticosteroids for maintenance therapy of Psoriasis on thin skin
      4. Nail Psoriasis with 1-2 nails involved (Calcipotriene/Betamethasone Dipropionate with Tazarotene)
    2. Medications
      1. Calcipotriene (Dovonex)
        1. Creams or ointments are applied once to twice daily
        2. Also available as a foam, or a combination with Betamethasone gel for use on scalp
      2. Calcitriol (Vectical)
        1. May be less irritating than Calcipotriene (Dovonex)
    3. Combinations
      1. May be used in combination with Phototherapy
        1. Apply AFTER Sun Exposure or Phototherapy to prevent drug inactivation with UV exposure
      2. Typically used in combination with Topical Corticosteroids (esp. for acute exacerbation)
        1. Spares Corticosteroids and combination is more effective than either drug alone
        2. Apply as a 1:1 mixture with Corticosteroid
          1. Alternatively apply on different days (e.g. weekend steroids, weekday Vitamin D)
      3. Methotrexate
        1. May spare Methotrexate dosing
    4. Adverse Effects: Risk of Hypercalcemia in high dose exposure and Renal Insufficiency
      1. Limit to 75 g/week for <30% BSA involved
      2. Limit to 50 g/week in children age 6 to 12 years
    5. Efficacy
      1. Benefits may be delayed 6 to 8 weeks
  5. Retinoids
    1. Acritretin (Soriatane, oral)
    2. Tazarotene (Tazorac, topical)
      1. Apply cream or gel every night to affected areas
      2. More irritating than Calcipotriene
      3. Contraindicated in pregnancy (Teratogenic)
      4. Efficacy
        1. As effective as Corticosteroids, but with longer disease-free periods
        2. Also effective in palmar-plantar Psoriasis and nail Psoriasis
        3. Consider in combination with Phototherapy
  6. Calcineurin Inhibitor (Tacrolimus, Pimecrolimus)
    1. Indications
      1. Common alternative to Corticosteroids for maintenance therapy of Psoriasis on thin skin
        1. Less skin atrophy than with Corticosteroids
    2. Agents
      1. Tacrolimus 0.1% cream
      2. Pimecrolimus 0.1% cream
    3. Dosing
      1. Start with daily therapy for 4 weeks until Plaques improve
      2. Next, taper to twice weekly treatment to suppress flares
      3. Do NOT apply under Occlusion
    4. Efficacy
      1. Effective in facial and intertriginous Psoriasis
      2. Lebwohl (2004) J Am Acad Dermatol 51:723-30 [PubMed]
    5. Adverse effects
      1. Risk of Skin Cancer and Lymphoma (especially in combination with UV Light Therapy)
  7. Novel newer agents (expensive and unclear efficacy in comparison with established agents)
    1. Aryl Hydrocarbon Receptor Agonists (AhR Agonists)
      1. Roflumilast (Vtama) 1% Cream applied once daily
        1. Approved only for adults
        2. Considered safe for longterm use, including in regions of thin skin (e.g. groin, face)
        3. Adverse effects include Folliculitis in up to 20% of patients
    2. Phosphodiesterase 4 Inhibitors (PDE4 Inhibitors)
      1. Similar to Eucrisa, a PDE4 Inhibitor indicated in Eczema
      2. Tapinarof (Zoryve) 0.3% cream applied once daily
        1. Approved for age 12 and older
        2. Considered safe for longterm use, including in regions of thin skin (e.g. groin, face)
        3. Adverse effects include Diarrhea, Headache
    3. References
      1. (2022) Presc Lett 29(10): 58-9
  8. Poorly tolerated topicals (Calcipotriene has largely replaced these)
    1. Historically used with UVB light exposure
    2. Anthralin 0.1% (Anthra-Derm)
      1. As effective as Calcipotriene
      2. Adverse effects include perilesional erythema, skin staining, burning Sensation
      3. Avoid applying to face or other sensitive areas, and avoid applying for longer than 2 hours
    3. Coal Tar (e.g. Zetar)
      1. Effective and inexpensive
      2. Consider in patients who can not afford other options
      3. More effective than Calcipotriene
      4. Avoid in pregnancy and Lactation
      5. Adverse effects include Folliculitis, Contact Dermatitis, Phototoxic Dermatitis

XIX. Management: Narrowband Ultraviolet Light (UVB)

  1. Indications
    1. Plaque Psoriasis or Guttate Psoriasis 10 to 25% BSA involved, refractory to topical agents
  2. Adverse Effects
    1. Inconvenient (multiple visits per week)
    2. Non-melanoma Skin Cancer (esp. PUVA)
  3. Efficacy
    1. Cost-effective and decreases overall Topical Medication use
  4. Protocols
    1. Ultraviolet B exposure alone
    2. Ultraviolet B and 12 days of Coal Tar Pretreatment (children)
    3. Ultraviolet A exposure with psoralen (PUVA)
      1. Increased risk of non-melanoma Skin Cancer

XX. Management: Systemic Preparations

  1. General
    1. Most agents are higher risk for systemic adverse effects and very expensive
    2. Indicated for moderate to severe Psoriasis
      1. Refractory to topical agents and UVB Therapy
      2. Involves >5% body surface area (BSA)
  2. Immunosuppressants
    1. Methotrexate
      1. Typically trialed as a first-line systemic agent (unclear efficacy)
      2. Start with oral Methotrexate
        1. May consider Methotrexate SQ if inadequate oral effect, or significant gastrointestinal effects
      3. See Methotrexate for monitoring guidelines
      4. Folic Acid 1-5 mg daily (except for the day Methotrexate is taken)
        1. Reduces adverse effects (Mouth Sores, gastrointestinal effects)
      5. Indications to switch therapy to other systemic agent (or to add in combination with Methotrexate)
        1. Psoriasis Area and Severity Index Score fails to improve 25% after 4 weeks on Methotrexate
    2. Cyclosporine
      1. Used as a rescue agent for flares in refractory cases for up to 12 weeks
      2. Monitor Blood Pressure and Renal Function (see Cyclosporine for monitoring)
  3. Systemic Retinoids (oral)
    1. Acitretin (Soriatane)
      1. Slow onset over 3-6 months
      2. Most effective in combination with Phototherapy (and Corticosteroids, Calcipotriene)
      3. Similar adverse effects to Accutane
        1. Highly Teratogenic (do not use in pregnancy)
        2. Teratogenicity lasts for 3 years after the medication has been used
  4. Phosphodiesterase Inhibitor (Type 4)
    1. Apremilast (Otezla)
      1. Does not require lab monitoring
      2. Indicated for mild to moderate Psoriasis (released in U.S., 2015)
      3. Adverse effects include Diarrhea, Nausea, Headache as well as weight loss and depression
      4. Avoid use with Strong Cytochrome P450-3A4 Inducers (e.g. Rifampin, Carbamazepine)
  5. Biologic Agents
    1. General
      1. Very expensive agents ($10k to >$20k/year)
      2. More effective than Methotrexate
      3. Insurance approval typically requires Methotrexate failure first
      4. Live Vaccines are contraindicated with on Biologic Agents
      5. Most effective agents in severe Chronic Plaque Psoriasis: Infliximab, Bimekizumab, Ixekizumab
        1. Sbidian (2023) Cochrane Dabatase Syst Rev (7): CD011535 [PubMed]
    2. Tumor Necrosis Factor Inhibitor (Anti-TNF Agents)
      1. See TNF Inhibitor for precautions and complications
      2. Adalimumab (Humira)
        1. Preferred TNF agent
      3. Etanercept (Enbrel)
        1. Less effective than Adalimumab (Humira) and Ustekinumab (Stelara)
        2. Leonardi (2003) N Engl J Med 349:2014-22 [PubMed]
      4. Infliximab (Remicade)
        1. More adverse effects than other TNF agents
        2. Winterfield (2004) Dermatol Clin 22:437-47 [PubMed]
    3. Interleukin 23 Inhibitors: Indicated in Plaque Psoriasis (Adults)
      1. Guselkumab (Tremfya)
        1. Dosing: 100 mg SQ at Week 0, Week 4 and then every 8 weeks
      2. Risankizumab (Skyrizi)
        1. Dosing: 150 mg SQ at Week 0, Week 4, then every 12 weeks
      3. Tildrakizumab (Ilumya)
        1. Dosing: 100 mg SQ at Week 0 and Week 4, and then every 12 weeks
    4. Interleukin 17 Inhibitors: Indicated in Plaque Psoriasis
      1. Brodalumab (Siliq)
        1. Adults: 210 mg SQ at week 0, week 1 and week 2, then every 2 weeks
      2. Ixekizumab (Taltz)
        1. Adults (and child weight >50 kg)
          1. Start: 160 mg SQ at week 0
          2. Next: 80 mg SQ at weeks 2, 4, 6, 8, 10, 12
          3. Next: 80 mg SQ every 4 weeks
        2. Child age >=6 years, weight <50 kg
          1. Weight 25 to 50 kg: 80 mg at week 0, then 40 mg every 4 weeks
          2. Weight <25 kg: 40 mg at week 0, then 20 mg every 4 weeks
      3. Secukinumab (Cosentyx)
        1. Adults: 300 mg SQ at Weeks 0,1,2,3 and 4, and then every 4 weeks
        2. Child (age>=6 years)
          1. Weight <50 kg: 75 mg SQ at Weeks 0,1,2,3 and 4, and then every 4 weeks
          2. Weight >=50 kg: 150 mg SQ at Weeks 0,1,2,3 and 4, and then every 4 weeks
    5. Other mechanisms
      1. Deucravacitinib (Sotyktu)
        1. Tyrosine Kinase 2 inhibitor
        2. More effective than Apremilast (Otezla), but expensive and unclear if it will demonstrate Cardiovascular Risks of JAK Inhibitors
      2. Ustekinumab (Stelara)
        1. Interleukin-23 blocker
        2. Risk of worsening Inflammatory Bowel Disease
        3. Dosed every 2-4 weeks
  6. Experimental
    1. Thiazolidinedione (Actos)
      1. Appears effective in Psoriasis even in non-diabetics
      2. Only small trials support to date
      3. Ellis (2000) Arch Dermatol 136(5):609-16 [PubMed]
      4. Malhotra (2012) Evid Based Med 17(6):171-6 +PMID: 22522793 [PubMed]

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