Chapter 5 Part 1 Psoriasis PDF - Dermatology & Cosmetology PHAR435

Dermatology & Cosmetology PHAR435 Spring 2023-2024 Chapter 5- Part I Plaque Psoriasis 1  Introduction Psoriasis is a chronic, multifactorial, non- contagious, inflammatory, hyperprolifera...

Dermatology & Cosmetology PHAR435 Spring 2023-2024 Chapter 5- Part I Plaque Psoriasis 1  Introduction Psoriasis is a chronic, multifactorial, non- contagious, inflammatory, hyperproliferative epidermal disease. It is characterized by recurrent, well- demarcated, thickened, erythematous scaling plaques, with silvery white scales, resulting from increase in epidermal cell turnover rate. Although rarely life-threatening, the clinical appearance of psoriasis can be cosmetically disfiguring, and the disease can be physically and emotionally debilitating. 2  Epidemiology The prevalence of psoriasis in adults ranges from 1 to 8.5%, and in children from 0 to 2%. There is no clear gender predilection for psoriasis, but it may occur slightly more in females compared to males, and is less common in tropics and dark-skinned individuals. A bimodal peak of age of onset have been described: – The greatest incidence is between 30 and 39 years and a smaller peak occurs between 50 and 69 years. – However, psoriasis can be seen at any age and even severe psoriasis, may occur in the pediatric age group. 3  Genetic factors Psoriasis is complex and multifactorial. It is associated with interaction between environmental factors and specific genetic/immunological background. There is a significant genetic component in psoriasis About 40% of patients with psoriasis have at least one first- degree relative with the disorder. There are multiple genetic loci identified for psoriasis (psoriasis susceptibility loci PSORS 1→9) – PSORS1 located on human chromosome 6 is the strongest susceptibility locus, accounting for one-third to one-half of the genetic liability to psoriasis. Additional genes affecting Thelper cell functions, namely genes encoding IL-12 and IL-23 may also play a genetic role. 4 Triggering factors Physical or chemical injury of skin by cuts, burns, bites, trauma or infections Ultraviolet injury (sunburn) Infections by streptococci (mainly throat infections), staphylococci, acute viral infections, upper respiratory tract infections. Some medications: β-blockers, lithium, antimalarials (chloroquine, hydroxychloroquine), NSAIDs, aspirin, tetracycline, and steroid withdrawal Psychological stress Environmental factors like cold Endocrine and hormonal changes like menopause Overweight, obesity, and unbalanced diet Consumption of tobacco and alcohol **In many patients, sun exposure and hot weather tend to improve the lesions. 5  Pathophysiology Under influence of immune-mediated and genetic pathways, overactive T cells migrate to the epidermis, where they are not normally present. These T cells trigger immune responses along with their cytokines, including attack of healthy skin cells by mistake as if to heal a wound or to fight an infection. Dilation of blood vessels in the skin around the plaques. Various cytokines production: TNF-α, IL-2, IL-8, IL-10, and INF-γ. 🡪 Result in an increased production of skin cells, T cells and other white blood cells. 6  Pathophysiology Scaling and erythema are the result of hyperproliferation and abnormal differentiation of the epidermis, inflammatory cell infiltrates, and vascular dilatation. When compared with normal epidermis, this hyperproliferative state is characterized by: ✔ Increased numbers of cells undergoing DNA synthesis ✔ A shortened cell cycle time for keratinocytes ✔ A decreased turnover time of the epidermis (four days from basal cell layer to stratum corneum, compared with 28 days in normal skin) ✔ Abnormal differentiation Dead skin and white blood cells can't slough off quickly enough and build up in thick, scaly patches on the skin's surface. This usually doesn't stop unless treatment interrupts the cycle. 7 8  Clinical Manifestations Chronic and relapsing spontaneous exacerbations and remissions. Lesions start as small papules that grow and coalesce into plaques, ranging from less than 1 - 10 cm in diameter. They are well circumscribed, sharply demarcated, light pink to bright red in color, usually symmetrically distributed, with an overlying thick, opaque, silvery, scale that can be pulled off in layers. Recent bathing may remove scales, and application of moisturizers may make them temporarily invisible. Itching is minimal (in only 25% of patients). When lesions disappear the skin will be either hypopigmented or hyperpigmented. 9  Common sites of involvement Most common locations: Scalp Lumbar regions of the back External ear Extensor surfaces of the elbow and the knee Nail involvement includes: Pitting and onycholysis Occur in all psoriasis subtypes Fingernails and toenails are involved in 50% and 35% of all patients respectively Psoriatic arthritis occurs in 7% of patients, and it involves the joints. It is often asymmetric in joint involvement, and can result in disability and deformity. 10 Plaque Psoriasis (Psoriasis Vulgaris) Most common type 11 Nails & Joint Psoriasis 12 13  MANAGEMENT I- Lifestyle Modifications - Avoiding psychological distress. - Avoiding physical, chemical, or UV injury of the skin. - Weight loss and hypocaloric diet for overweight or obese adults. - Avoidance of rubbing/friction. - Bathing in lubricating bath products 2-3 times per week. - Removal of scales by gentle rubbing with a soft cloth. - Application of emollients to lesions within 3 minutes of bathing. 14  Moisturizers Emollients are frequently used during therapy-free periods to minimize skin dryness that can lead to early recurrence. Benefits: – Hydrate skin and minimize evaporation – Create barrier against environment – Eliminate scaling – Control pruritus Available as lotions, creams, or ointments Emollients often need to be applied several times per day (about four times) to achieve a beneficial response. 15 II- Pharmacotherapy Mild to moderate disease: localized or scattered lesions covering less than 3% of the BSA – Topical treatment Moderate to severe disease: affecting more than 3% of the BSA or affecting crucial body areas such as the hands, feet, face, or genitals – Topical plus systemic treatment 16 17  Topical Therapy First line: 1- Corticosteroids 2- Vitamin D analogues 3- Tazarotene Second line: 4- Salicylic acid 5- Anthralin 6- Coal tar 18  Topical corticosteroids The cornerstone of treatment for mild psoriasis; well tolerated and efficacious The most effective topical agent for psoriasis plaques. Anti-inflammatory, antiproliferative, immunosuppressive, and vasoconstrictive Dosing: – Can be used as mono-therapy 1-2 times daily – Can be combined with other topical agents, UV light and systemic agents Duration of treatment – Class 1 steroids (super high potency): available data for 2-4 weeks of treatment – Less potent agents: Optimal endpoint unknown (preferred face & flexures) Examples: betamethasone, hydrocortisone, mometasone, clobetasole. Bryhali® (halobetasol propionate) lotion, 0.05% and 0.01%, new agent for the treatment of moderate-to-severe plaque psoriasis in patients 18 years and older. SE: Skin atrophy, telangiectasias, striae, purpura, contact dermatitis 19  Topical Calcineurin Inhibitors Topical calcineurin inhibitors bind to calcineurin, blocking its phosphorylation and thus, inhibiting T-cell activation and the synthesis of several proinflammatory cytokines that play a critical role in the pathogenesis of psoriasis. Although not FDA approved for psoriasis, tacrolimus and pimecrolimus are often used in the treatment of psoriasis. They are especially helpful on thinner skin, such as facial and intertriginous areas, and are used as steroid-sparing agents for prolonged use (>4 weeks). Treatment duration up to 8 weeks. S.E.: burning, pruritus, and flushing with alcohol ingestion. BBW: long-term, intermittent use of pimecrolimus or tacrolimus could lead to an increased incidence of lymphoma. 20  Vitamin D Analogue Calcipotriene (Daivonex®) – Synthetic analogue of vitamin D3 – Affects cellular differentiation and proliferation, regulates apoptosis and demonstrates an immunomodulatory effect – Odorless and nonstaining and therefore cosmetically acceptable – Does not cause long-term skin thinning – Side effects: pruritus, burning, edema, peeling, dryness, and erythema, which diminish with ongoing treatment – Long term use up to 52 weeks is recommended for mild to moderate psoriasis Available in combination with betamethasone (Daivobet®) for 4-12 weeks – More effective than either ingredient alone A newer foam formulation is available and is useful for scalp psoriasis. UVA can decrease the concentration of calcipotriene on the skin and thick layers of calcipotriene can block UVB. – Vitamin D analogues can be used in conjunction with phototherapy but should be applied after the phototherapy treatment. 21  Tazarotene Topical vitamin A derivative, third generation retinoid – Modulates cell proliferation and differentiation Efficacy: – It is less potent than vitamin D analogues and moderate or potent local corticosteroids – Has limited use as monotherapy – Best used in combination with topical corticosteroids for mild to moderate psoriasis, and this limits irritation caused by tazarotene – Topical tazarotene can be particularly helpful for palmar-plantar psoriasis and nail psoriasis Dosing & duration: – It is normally used for 12 weeks and applied to affected area qd (0.05 or 0.1% cream or gel) Pregnancy category X  Salicylic Acid The most widely used and oldest keratolytic. Available in concentrations ranging from 0.5% to 60% in a number of vehicles. Removes scales, allowing topical corticosteroids and other topical medications to better reach target tissues. Efficacy: – It is particularly useful in thick plaque psoriasis – It can be used for 8-16 weeks for the treatment of mild to moderate psoriasis – Salicylic acid plus steroid better efficacy than steroid monotherapy Dexamethasone/Betamethasone/Mometasone + SA 3% Moderate to severe psoriasis (body surface area ≤20%) Application on large areas and in concentrations greater than 10% results in toxicity Salicylic acid may reduce the action of vitamin D analogues. – The acid pH of salicylic acid will inactivate calcipotriene and reduce its effectiveness 23  Anthralin Possesses antiproliferative activity on human keratinocytes. Inhibits DNA synthesis. SEs: Inflammation, irritation, and staining of skin and clothing are often therapy-limiting effects. It is not the first or second drug of choice due to irritation problems of normal skin surrounding lesions and staining of the skin. Usually it is applied qd in the evening and allowed to remain overnight then removed by washing. Topical anthralin for 8-12 weeks can be used for the treatment of mild to moderate psoriasis. Short contact (up to 2 hours per day) anthralin is recommended to limit adverse side effects. 24  Coal Tar Numerous hydrocarbon compounds formed from distillation of coal. Exact mechanism of action is not fully understood, but when applied to normal skin, has a cytostatic effect with epidermal thinning. Inhibits DNA synthesis, this down regulated epidermal proliferation rate approaches a normal rate of proliferation. Available in OTC shampoos (used in scalp psoriasis) and creams. SEs: time-consuming and messy, photosensitivity, and black staining or discoloration of skin and clothes. Shampoos are most commonly used (e.g. Neutrogena T-gel) as they are easily applied and rinsed with minimal staining. Coal tar preparations are recommended for the treatment of mild to moderate psoriasis. 25  New FDA Approved Topical Products Drug Administration Drug Class Patient Psoriasis Side effects Population Indication Roflumilast topical PDE-4 inhibitor ≥12 years Mild-to-severe Diarrhea, application plaque headache, trouble once daily psoriasis including sleeping, nausea, intertriginous areas URTIs, and UTIs Tapinarof topical Aryl Adults Mild-to-severe Folliculitis, application hydrocarbon plaque nasopharyngitis, once daily receptor (AhR) psoriasis including skin rash, itching, modulating intertriginous areas redness, peeling, agent burning, or *similar to coal stinging, headache, tar flu 26  Phototherapy The improvement of psoriatic lesions with sun exposure led to the development of the idea of phototherapy in psoriasis. Exposure to UV inactivates immune cells and reduces release and synthesis of inflammatory mediators, thereby reducing dermal inflammation and epidermal cell turnover. Patients should attend phototherapy sites 2-3 times per week. Contraindications: – Previous skin malignancy, and photosensitivity. – The patient should not be concomitantly taking any photosensitizing drugs. Exposure to light (both dose and time) are gradually increased as treatment progresses. 20-30 treatments are needed. 27  Phototherapy Phototherapy Details UVB - Given 3 times/week - Can be used in combination with tar or oral acitretin for thick, chronic psoriasis - Can be used in children and pregnant women Targeted UVB - Used when 200 treatments) or radiation therapy, abnormal renal function, uncontrolled hypertension, simultaneous administration of NB-UVB due to the increase risk of photocarcinogenesis (this combination is efficacious when used sequentially) 32  Acitretin Vitamin A derivative. Acitretin's effects are thought to be induced by controlling cellular differentiation and proliferation, reducing inflammation and keratinization, and inhibiting neutrophil chemotaxis. Synergistic effect in combination with PUVA/UVB, where less UV exposure is needed. Combination therapy 🡪 better outcome. The efficacy of acitretin monotherapy in chronic plaque psoriasis is limited. SEs: dryness of mucous membranes, thinning of hair, erythema of palms, itching, hepatotoxicity, raised blood lipids. Acitretin is metabolized to a teratogenic derivative, so women must use effective contraception during use and for 3 years afterwards. – Males have shown residual amounts of acitretin in seminal fluid, which appears to pose little risk to the fetus Patients should not donate blood during therapy and 3 years after discontinuation..33  Apremilast (Otezla®) Indications – Treatment of moderate to severe plaque psoriasis – Treatment of active psoriatic arthritis in adults Place in therapy – Oral alternative to methotrexate and retinoids Pregnancy category C Received FDA approval Dosing: 30 mg orally twice daily on September, 2014 Precaution CrCl < 30 ml/min (reduce dose to no more than 30 mg qd) 34  Apremilast (Otezla®) Pharmacology – Phosphodiesterase-4 inhibitor, with an anti- inflammatory effects that are not completely understood. – Reduce synthesis of several inflammatory mediators Adverse effects – Common: Diarrhea, headache, nausea – Serious: Weight loss and depression 35  New FDA Approved Oral Products Drug Administra Drug Class Patient Psoriasis Side effects tion Population Indication Deucravacitinib Oral (6mg Selective ≥18 years Moderate-to- NOTE: Avoid use in (Sotyktu*) oral tablets inhibitor of severe plaque patients with TB or FDA approved taken once tyrosine kinase psoriasis in adults any other active Sep-2022 daily) 2 (TKY2) who are candidates infection, even for systemic with live vaccines therapy or SE: phototherapy Infection including pneumonia and URTI, acne vulgaris, oral ulcers, inc liver enzymes, inc TG, rhabdomyolysis 36  Combinations for Moderate to Severe Psoriasis Topical calcipotriene + standard dose methotrexate Calcipotriene/betamethasone + low dose cyclosporine Calcipotriene + standard dose acitretin All topical corticosteroids can be used in combination with any biologics Calcipotriene/betamethasone + standard dose adalimumab 37  Biological Agents Indicated for moderate to severe psoriasis in patients unresponsive or not candidates for systemic therapy or phototherapy. The available biologics for psoriasis have excellent short-term and long-term efficacy and favorable tolerability. Anti-TNF agents – Etanercept (Enbrel®) SC injection – Infliximab (Remicade®) IV infusion – Adalimumab (Humira®) SC injection – Certolizumab pegol (FDA approved in 2018) (Cimzia®) SC injection 38  Biological Agents Monoclonal Antibody Against IL-12 and IL-23 – Ustekinumab (Stelara®) SC injection Monoclonal Antibody Against IL-17 – Secukinumab – Ixekizumab – Brodalumab Monoclonal Antibody Against IL-23 – Guselkumab – Tildrakizumab Monoclonal Antibody Against IL-23 and IL-39 – Risankizumab (FDA approved in 2019) 39 40  Biological Agents General Recommendations Contraindicated in Increase the risk of Do not use with live patients with active, malignancy vaccines serious infections TNF inhibitors Hepatitis B All are pregnancy worsen congestive reactivation category B heart failure Common adverse Baseline Monitoring: effect: PPD Injection site reactions & LFT’s, CBC, and hepatitis infections profile 41