Chapter 5 - Part I: Plaque Psoriasis

Chapter 5 - Part I: Plaque Psoriasis

• Psoriasis is a chronic, multifactorial, non-contagious, inflammatory, hyperproliferative epidermal disease.
• Characterized by recurrent, well-demarcated, thickened, erythematous scaling plaques with silvery white scales, resulting from increased epidermal cell turnover.
• Although rarely life-threatening, it can be cosmetically disfiguring and physically/emotionally debilitating.

Epidemiology

• Prevalence in adults ranges from 1-8.5%, and in children from 0-2%.
• No clear gender predilection, but slightly more common in females.
• Less common in tropical and dark-skinned individuals.
• Bimodal peak of age of onset:
  • Greatest incidence between 30-39 years.
  • Smaller peak between 50-69 years.
  • Can also occur in the pediatric age group.

Genetic Factors

• Complex and multifactorial, associated with interaction between environmental and specific genetic/immunological factors.
• Significant genetic component: about 40% of patients have at least one first-degree relative with the disorder.
• Multiple genetic loci identified (PSORS 1-9).
  • PSORS1 on chromosome 6 is the strongest susceptibility locus, accounting for 1/3 to 1/2 of the genetic liability to psoriasis.
• Additional genes affecting T helper cell functions (e.g., IL-12 and IL-23) may play a genetic role.

Triggering Factors

• Physical or chemical skin injuries (cuts, burns, bites, trauma).
• UV injury (sunburn).
• Infections (streptococci, staphylococci, acute viral infections, upper respiratory tract infections).
• Medications (beta-blockers, lithium, antimalarials, hydroxychloroquine, NSAIDs, aspirin, tetracycline, and steroids).
• Psychological stress.
• Environmental factors (e.g., cold).
• Endocrine/hormonal changes (e.g., menopause).
• Overweight, obesity, and unbalanced diet.
• Tobacco and alcohol consumption.
• Sun exposure and hot weather may improve lesions in some patients.

Pathophysiology

• Overactive T cells migrate to the epidermis, where they are not normally present.
• Immune responses target healthy skin cells, similar to healing a wound or fighting an infection.
• Dilation of blood vessels occurs around plaques.
• Various cytokines (TNF-α, IL-2, IL-8, IL-10, and INF-γ) are produced.
  • This results in increased skin cell production, along with T cells and other white blood cells.
• Scaling and erythema result from hyperproliferation and abnormal differentiation in epidermis combined with inflammatory cell infiltration and vascular dilation.
• Increased cell numbers undergoing DNA synthesis, shortened keratinocyte cell cycle time, and decreased epidermal turnover time (4 days versus 28 days in normal skin).
• Abnormal differentiation prevents dead skin cells from sloughing off adequately and builds up into thick, scaly patches on the surface.

Histopathology of Psoriasis

• Characteristics observed in the histopathology of psoriasis include:
  • Presence of a "silver" scale on the surface.
  • Erythematous base.
  • Increased Langerhans cells.
  • Persistence of nuclei in the stratum corneum (parakeratosis).
  • Microabscesses.
  • Dilated and tortuous papillary vessels.
  • Edema and inflammation of the dermis.

Clinical Manifestations

• Chronic relapsing disease with exacerbations and remissions.
• Lesions start as small papules, growing and merging into plaques ranging from less than 1 to 10 cm in diameter.
• Well-circumscribed, sharply demarcated, light pink to bright red color; usually symmetrically distributed.
• Thick, opaque, silvery scale that can be peeled off in layers.
• Recent bathing or moisturizer application can temporarily make scales less visible.
• Minimal itching, affecting only approximately 25% of patients.
• Skin may be hypopigmented or hyperpigmented after lesions disappear.

Common Sites of Involvement

• Most common: scalp, lumbar regions of the back, external ear, extensor surfaces of elbows and knees.
• Nail involvement: pitting and onycholysis, affects fingernails and toenails in 50% and 35% of patients, respectively.
• Psoriatic arthritis: affects 7% of patients, involving joints, often asymmetric with resultant disability and deformity.

Plaque Psoriasis (Psoriasis Vulgaris)

• Most common type of psoriasis.

Nails & Joint Psoriasis

• Images illustrating lifting/splitting of nails and swelling of joints.

Psoriasis Coverage & Severity

• Severity levels (mild, moderate, severe) are defined by the percentage of body surface area affected.
  • Mild: <3%
  • Moderate: 3-10%
  • Severe: >10%
• 80% of patients have mild disease; 20% have moderate to severe disease.

Lifestyle Modifications

• Avoidance of psychological distress.
• Avoidance of physical, chemical, or UV injury to the skin.
• Weight loss and hypocaloric diet for obese adults.
• Avoidance of rubbing/friction.
• Bathing with lubricating products 2-3 times weekly.
• Removal of scales by gentle rubbing with a soft cloth.
• Application of emollients to affected skin within 3 minutes of bathing.

Moisturizers

• Emollients often used during therapy-free periods and in combination to minimize skin dryness.
• Benefits include moisturizing, minimizing evaporation, creating a barrier against the environment, eliminating scaling, and controlling itching.
• Available as lotions, creams, or ointments and often require multiple applications per day.

Pharmacotherapy

• Mild to Moderate Disease (localized or scattered lesions <3% BSA): Topical treatment.
• Moderate to Severe Disease (affecting more than 3% BSA or affecting crucial body areas like hands, feet, face, or genitals): Topical plus systemic treatment.

Topical Therapy

• First Line: Corticosteroids, Vitamin D analogues, Tazarotene.
• Second Line: Salicylic acid, Anthralin, Coal tar.

Topical Corticosteroids

• Cornerstone of treatment for mild psoriasis.
• Well-tolerated and often effective.
• Anti-inflammatory, antiproliferative, immunosuppressory, and vasoconstrictive.
• Dosing: 1-2 times daily.
• Can be combined with other topical agents, UV light, and systemic agents.
• Possible side effects: skin atrophy, telangiectasias, striae, purpura, and contact dermatitis.
• Examples: betamethasone, hydrocortisone, mometasone, clobetasole, halobetasol propionate.

Topical Calcineurin Inhibitors

• Bind to calcineurin; blocking phosphorylation and inhibiting T-cell activation.
• Tacrolimus and pimecrolimus are often used, though not FDA-approved for psoriasis, and are used as steroid-sparing agents.

Vitamin D Analogue (Calcipotriene)

• Synthetic vitamin D3 analogue.
• Affeects cellular differentiation and proliferation; regulates apoptosis; immunomodulatory.
• Odorless and non-staining; cosmetically acceptable.
• Long-term use (up to 52 weeks) recommended for mild to moderate psoriasis.

Tazarotene

• Topical vitmain A derivative; third-generation retinoid.
• Modulates cell proliferation and differentiation.
• Less potent than vitamin D analogues and moderate/potent local corticosteroids.
• Best used in combination with corticosteroids, particularly helpful for palmar-plantar and nail psoriasis.
• Dosing: 0.05 or 0.1% cream or gel.
• Pregnancy Category X.

Salicylic Acid

• Keratolytic; widely used and oldest.
• Available in concentrations ranging from 0.5% to 60%.
• Removes scales, allowing better access for topical corticosteroids.
• Effective in thick plaque psoriasis.
• Used for 8-16 weeks for mild to moderate disease.
• Side effects: High concentrations can result in toxicity.

Anthralin

• Possesses antiproliferative activity on human keratinocytes.
• Inhibits DNA synthesis.
• Often causes irritation and staining of skin and clothing, making it less of a first or second line treatment.
• Usually applied overnight.

Coal Tar

• Numerous hydrocarbons formed from the distillation of coal.
• Exact mechanism of action is not fully understood.
• Epidermal thinning; cytostatic effect.
• Inhibits DNA synthesis.
• May be used in shampoos for scalp.
• Side effects; time-consuming, messy, photosensitivity, and black staining or discoloration of skin and clothing.

Phototherapy

• Improvement of psoriatic lesions by exposure to UV light.
• UV inactivates immune cells, reducing dermal inflammation and epidermal cell turnover.
• Patients attend phototherapy sites 2-3 times per week.
• Contraindications: history of skin cancer, photosensitivity, and concurrent use of photosensitizing drugs.
• UVB, Targeted UVB, UVA, Excimer laser.

Systemic Therapy

• Used for patients with moderate-to-severe psoriasis.
• Widespread disease that has failed to respond to topical & UV therapy.
• Concomitant psoriatic arthritis.
  • Examples: Methotrexate, Cyclosporine, Acitretin, Apremilast.

Methotrexate

• Reduces skin cells and T cell proliferation by inhibiting dihydrofolate reductase.
• Inhibits DNA synthesis and promotes T cell apoptosis.
• Given once weekly as a tablet or injection.
• Gradually increasing low doses to control psoriasis.
• Side effects: hepatotoxicity, myelosuppression, GI side effects.

Cyclosporine

• Immunosuppressant; oral calcineurin inhibitor.
• Depresses cell-mediated immune responses by inhibiting helper T cell function.
• Effective for inflammatory types of psoriasis, due to rapid onset of action.
• Dosing: Orally, in two divided doses per day.
• Duration: Ideally restricted to 12 weeks; typically cannot be used concurrently with PUVA or radiation.
• Side effects: Nausea, renal impairment, hypertension.

Acitretin

• Vitamin A derivative.
• Effects though to be induced by controlling cellular differentiation, proliferation, reducing inflammation and keratinization, and inhibiting neutrophil chemotaxis.
• May be used in synergy with PUVA/UVB treatments.

Apremilast

• Indications: Moderate-to-severe plaque psoriasis; active psoriatic arthritis in adults.
• Oral alternative to methotrexate and retinoids (pregnancy category C).
• Dosing: 30 mg orally twice daily.
• Side effects: Diarrhea, headache, nausea, weight loss, depression.

Deucravacitinib (Sotyktu)

• Oral; Selective inhibitor of tyrosine kinase 2 (TYK2).
• Moderate-to-severe plaque psoriasis in adults who are candidates for systemic therapy or phototherapy; may be used in combination.

New FDA-Approved Topical Products (Table)

• Roflumilast and Tapinarof

Biological Agents

• MOA involves targeting cytokines such as IL-12, IL-23, IL-17, or TNF-alpha to treat moderate-to-severe psoriasis.

Biological Agents (General Recommendations)

• Contraindicated in patients with active, serious infections
• Increases risk of malignancy
• Avoid use with live vaccines
• TNF inhibitors may worsen congestive heart failure.
• Common adverse effect: Injection site reactions and Infections
• Baseline Monitoring: PPD, LFTs, CBC, and hepatitis profile.
• All are pregnancy category B

Combinations for Moderate to Severe Psoriasis

• Topical calcipotriene, standard-dose methotrexate
• Calcipotriene/betamethasone, low-dose cyclosporine
• Calcipotriene, standard-dose acitretin
• All topical corticosteroids with any biologics
• Calcipotriene/betamethasone with standard-dose adalimumab

Biological Agents

• Indicated for moderate-to-severe psoriasis in unresponsive or ineligible patients for systemic or phototherapy.
• Excellent short and long-term efficacy and tolerability.
  • Anti-TNF agents (etanercept, infliximab, adalimumab, certolizumab).
• Monoclonal Antibody Against IL-12 and IL-23 (ustekinumab).
• Monoclonal Antibody Against IL-17 (secukinumab, ixekizumab, brodalumab).
• Monoclonal Antibody Against IL-23 (guselkumab, tildrakizumab).
• Monoclonal Antibody Against IL-23 and IL-39 (risankizumab).

This quiz focuses on the characteristics, epidemiology, and genetic factors of plaque psoriasis. Learn about this chronic inflammatory skin condition, its prevalence across different age groups and demographics, and its multifactorial nature. Test your knowledge on the impact of genetics and environment on the onset of psoriasis.