Hyperplasia

Psoriasis

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Psoriasis, Chronic Plaque Psoriasis, Guttate Psoriasis, Inverse Psoriasis, Flexural Psoriasis, Erythrodermic Psoriasis, Psoriatic Onychodystrophy, Psoriatic Nail Pitting, Psoriatic Onycholysis

  • Epidemiology
  1. Bimodal peaks
    1. Young adulthood (ages 16 to 22 years old)
    2. Older age (late 50s)
  2. Prevalence: 1-2% of general population (U.S.)
  3. Men and women affected equally
  • Pathophysiology
  1. Underlying genetic predisposition is common (30% with Psoriasis also have a first degree relative with Psoriasis)
    1. Pathogenesis is likely a combination between genetic predisposition and exposure to inciting triggers
  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
  • Risk Factors
  • Associated environmental factors
  1. Suppressed by:
    1. Sun and humidity
  2. Provocative
    1. Injury to skin (Koebner Reaction)
    2. Streptococcal Pharyngitis
    3. Emotional upset
    4. Tobacco Use
    5. Obesity
    6. Alcohol Abuse
    7. HIV Infection (severe exacerbations)
    8. Medications
      1. Antimalarials
      2. Beta Blockers (e.g. Propranolol)
      3. Lithium
      4. NSAIDS
  • Symptoms
  1. Pruritus is present in >80% of psorisis
    1. Psora is greek for itching
  • Signs
  • Chronic Plaque Psoriasis (90% of cases)
  1. Description
    1. Widespread
    2. Sharply demarcated
    3. Bright pink, red or salmon-colored Plaques
    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
  • Signs
  • Associated findings
  1. Location specific signs
    1. Nail (Psoriatic Onychodystrophy)
      1. Lifetime Prevalence in up to 90% of Psoriasis patients (esp. Fingernails)
      2. 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. Gluteal cleft
      1. Eroded pinkness in crease
    3. Penis (genital involvement in 40% of cases)
      1. Pink Macules or Plaques on penis
    4. Large joints
      1. Hyperkeratosis over elbows, knees, and ankles
    5. Tongue
      1. Geographic Tongue (rare)
  2. Uncommon Clinical Variants
    1. Guttate Psoriasis (drop-like)
      1. Uncommon, accounting for only 2% of Psoriasis cases
      2. Typically affects younger patients, under age 30 years
      3. Trunk lesions are 1-10 mm Papules with fine scale
      4. Commonly occurs following Streptococcal Pharyngitis or Upper Respiratory Infection
    2. Inverse Psoriasis (flexural)
      1. Less scale present than in Plaque form
      2. Affects flexor surfaces (inframammary, axillary and inguinal folds)
      3. Affects perineal and intergluteal regions
    3. Palmoplantar Pustulosis (Pustular Psoriasis)
      1. Likely represents a distinct condition from Psoriasis
      2. Pustules on palms and soles without Plaques
      3. von Zumbusch variant causes severe, acute, life-threatening sub-type
    4. Erythrodermic Psoriasis (Erythroderma)
      1. Broad-spread generalized erythema
      2. Systemic symptoms are typically present
  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
  • Differential Diagnosis
  1. Lichen Simplex Chronicus
  2. Nummular Eczema
  3. Seborrheic Dermatitis
  4. Tinea Corporis
  5. Group A Beta Hemolytic Streptococcus
    1. May present as Guttate Psoriasis in children
    2. Obtain ASO Titer and Throat Culture
  • Associated Conditions (related to psoriatic medications)
  1. Inflammatory Bowel Disease (Crohns' Disease or Ulcerative Colitis)
    1. Risk increased 3.8 to 7.5x
  2. Celiac Disease
  3. Malignancy
    1. Squamous Cell Skin Cancer
      1. Risk increased 14x associated with PUVA in caucasians
    2. Lymphoma
      1. Risk increased 1.3 to 3x
  4. Major Depression
    1. Prevalence: 60% of Psoriasis patients
  5. Other associated conditions with increased risk
    1. Myocardial Infarction
  • Management
  • General Measures
  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)
  4. Consider Emollient only periods of steroid holiday
  • Management
  • Pregancy
  1. Most Psoriasis improves during pregnancy and worsens postpartum (but variable across pregnancies)
  2. First-line
    1. Topical Skin Lubricants
    2. Topical low to moderate potency Topical Corticosteroids
    3. UVB Phototherapy
  3. Severe cases (after first trimester)
    1. TNF Inhibitors
    2. Cyclosporine
    3. Systemic Corticosteroids
  4. References
    1. Erlandson (2023) Am Fam Physician 107(2): 152-8 [PubMed]
  • Management
  • Approach - Moderate Chronic Plaque Psoriasis
  1. Trunk and extensor surface involvement
    1. Initial and exacerbation therapy (<4 weeks only)
      1. Protocol 1: Steroid and Calcipotriene
        1. High potency Topical Corticosteroid each morning
        2. Calcipotriene applied every evening
      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)
  2. Flexor surface involvement
    1. Moderate Topical Corticosteroids (<4 weeks) or
    2. Tacrolimus or Pimecrolimus
  3. Scalp involvement
    1. Exacerbations
      1. Topical Corticosteroid (brief use)
      2. Example: Clobetasol 0.05% Shampoo
    2. Maintenance
      1. Anti-DandruffShampoo
      2. Examples: T-gel or selsun
  4. Adjuncts
    1. Lac-Hydrin or salicylic acid applied daily to soften Plaques
  • Management
  • Approach - Severe Chronic Plaque Psoriasis
  1. Criteria
    1. Psoriasis refractory to above therapy
    2. Chronic Plaque Psoriasis involving >5-20% of body
    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 Ultraviolet light below
    3. See Systemic Agents below
  • Management
  • Topical Preparations
  1. Topical Corticosteroids
    1. Consider limiting potent steroids to 2-4 weeks at a time
      1. Then rotate to lower potency steroids or decrease application frequency (e.g. twice weekly)
      2. Consider Emollient only periods until reexacerbation
    2. High Potency Topical Steroids (Class 2 to 5, usually indicated)
      1. Very high potency: e.g. Clobetasol (Temovate)
      2. High potency: e.g. Fluocinonide (Lidex)
    3. Low Potency Topical Steroids (e.g. Hydrocortisone 2.5%)
      1. Face
      2. Genitalia
      3. Forearms
      4. Intertriginous regions
      5. Maintenance Therapy
  2. Vitamin D based topicals (Calcipotriene, Calcitriol)
    1. Indicated for moderate Psoriasis involving 5-20% of body surface area
    2. Used alone or in combination with Phototherapy or Topical Corticosteroids
    3. Risk of Hypercalcemia in high dose exposure and Renal Insufficiency
    4. Preparations
      1. Calcipotriene (Dovonex)
      2. Calcitriol (Vectical)
        1. May be less irritating than Calcipotriene (Dovonex)
  3. Retinoid based topicals: Tazarotene (Tazorac)
    1. More irritating than Calcipotriene
    2. As effective as Corticosteroids, but with longer disease-free periods
    3. Do not use in pregnancy (Teratogenic)
  4. Immunosuppressant based topicals (Tacrolimus, Pimecrolimus)
    1. Indications
      1. Effective in facial and intertriginous Psoriasis (due to less skin atrophy than with Corticosteroids)
    2. Agents
      1. Tacrolimus 0.1% cream
      2. Pimecrolimus 0.1% cream
    3. Efficacy
      1. Effective in facial and intertriginous Psoriasis
      2. Lebwohl (2004) J Am Acad Dermatol 51:723-30 [PubMed]
    4. Adverse effects
      1. Risk of Skin Cancer and Lymphoma (especially in combination with UV Light Therapy)
  5. Adjunctive agents in combination with above
    1. Topical Salicylic Acid (Keratolytic Agent)
  6. 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
  7. 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
  • Management
  • Ultraviolet Light
  1. Risk of non-melanoma Skin Cancer
  2. Protocols
    1. Ultraviolet B exposure alone
    2. Ultraviolet A exposure with psoralen (PUVA)
      1. Increased risk of non-melanoma Skin Cancer
  • Management
  • Systemic agents (most are higher risk) for moderate to severe Psoriasis
  1. 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) reduces adverse effects (Mouth Sores, gastrointestinal effects)
    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. Etretinate
  2. 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
  3. Phosphodiesterase Inhibitor (Type 4)
    1. Apremilast (Otezla)
      1. Available as of 2015 in U.S.
      2. Does not require lab monitoring
      3. Expensive ($1875/month)
      4. Adverse effects include Diarrhea, Nausea, Headache as well as weight loss and depression
      5. Avoid use with Strong Cytochrome P450-3A4 Inducers (e.g. Rifampin, Carbamazepine)
  4. Biologic Agents (Cost from $10k to >$20k/year)
    1. Tumor Necrosis Factor (tnf) receptor blockers
      1. Adalimumab (Humira)
        1. Preferred TNF agent
      2. Ustekinumab (Stelara)
        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]
      5. Brodalumab (Siliq)
        1. Increased Suicide Risk
      6. Guselkumab (Tremfya)
    2. 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. Cosentyx (secukinumab)
        1. Interleukin-17a blocker available in U.S. in 2015
        2. Dosed every 8 to 12 weeks
      3. Ustekinumab (Stelara)
        1. Interleukin-23 blocker
        2. Risk of worsening Inflammatory Bowel Disease
        3. Dosed every 2-4 weeks
  5. 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]