Psoriasis Lecture Notes PDF

Psoriasis American academy of dermatology (AAD) Psoriasis Definition Psoriasis vulgaris is a genetic, systemic, inflammatory, chronic disorder characterized by scaly, erythematous patches, papules, and plaques that are often pruritic. It may be associated with other inflammatory disorde...

Psoriasis American academy of dermatology (AAD) Psoriasis Definition Psoriasis vulgaris is a genetic, systemic, inflammatory, chronic disorder characterized by scaly, erythematous patches, papules, and plaques that are often pruritic. It may be associated with other inflammatory disorders such as psoriatic arthritis, inflammatory bowel disease, and coronary artery disease. Psoriasis is a chronic disease that waxes and wanes. It is never cured. It affects males and females equally. Onset before the age of 40. Psoriasis Etiology Predisposing factors: Injury to the skin, infection, drugs, smoking, alcohol consumption, obesity, and psychogenic stress. Precipitating factors: A viral or streptococcal infection, or the use of β-adrenergic blockers. Exacerbating factors: Drugs (eg, lithium, nonsteroidal anti-inflammatory drugs [NSAIDs], antimalarials such as chloroquine, β-adrenergic blockers, and withdrawal of corticosteroids). Psoriasis Classification of psoriasis Plaque Inverse Erythrodermic Pustular Guttate Nail disease Psoriasis Pathogenesis of psoriasis  Psoriasis Signs and symptoms Psoriatic Pruritis lesions Pruritis may be severe in some patients and may require treatment to minimize excoriations from constant scratching. Psoriasis COMORBIDITIES ASSOCIATED WITH PSORIASIS MEDICAL COMORBIDITIES Autoimmune diseases Higher incidence of : Crohn’s disease and ulcerative colitis multiple sclerosis (MS). Metabolic syndrome Obesity, impaired glucose regulation, hypertriglyceridemia, reduced high-density lipoprotein, and hypertension Increased risk of developing cardiovascular morbidity and mortality. Psoriasis COMORBIDITIES ASSOCIATED WITH PSORIASIS MEDICAL COMORBIDITIES Cardiovascular diseases There is an increased risk of cardiovascular disease in patients with psoriasis. Even after correcting for the heart disease risk factors of smoking, diabetes, obesity, hypertension, and hyperlipidemia, the probability of myocardial infarction is higher in patients who are psoriatic. Psoriasis COMORBIDITIES ASSOCIATED WITH PSORIASIS MEDICAL COMORBIDITIES Lymphoma, melanoma, and nonmelanoma skin cancer Malignancies such as cutaneous T-cell lymphoma are associated with psoriasis. Melanoma and nonmelanoma skin cancer are associated with psoriasis treatments. PSYCHIATRIC/PSYCHOLOGIC COMORBIDITIES Depression/suicide Poor self esteem, sexual dysfunction, anxiety, depression, and suicidal ideation. Evaluation of psoriasis Psoriasis EVALUATION OF PSORIASIS SEVERITY The Psoriasis Area and Severity Index The Psoriasis Area and Severity Index (PASI) is a measure of overall psoriasis severity and coverage that assesses BSA and erythema, induration, and scaling. Typically, the PASI score is calculated before, during, and after a treatment to determine how well psoriasis responds to the treatment. Producing a score from 0 (no disease) to 72 (maximal disease severity). The PASI is an important research tool but is used infrequently in clinical practice. PASI calculator Psoriasis EVALUATION OF PSORIASIS The severity of psoriasis according to involved BSA: < 5%...... Mild 5% to 10%...... Moderate and>10% are considered severe disease, Management Psoriasis Management Desired outcomes Minimizing or eliminating the signs of psoriasis, Alleviating pruritus and minimizing excoriations. Reducing flare-up frequency. Ensuring appropriate management of associated comorbidities. Avoiding or minimizing adverse effects from treatments used. Providing cost-effective therapy. Providing guidance or counseling as needed (eg, stress reduction techniques). Maintaining or improving the patient’s quality of life. Ensuring that patients are partners in their own care. Psoriasis Management Non-pharmacological Stress reduction techniques Nonmedicated moisturizers: Aloe vera Use of fragrance-free products. Harsh soaps, detergents, and other skin irritants must be prohibited as they may worsen the skin condition. Trauma to the skin must always be avoided. Psoriasis can manifest around sites of skin trauma including surgery. The use of sun protection factor (SPF) of 30 or more. Loose-fitting clothes.  Topical agents Mild to moderate disease. Used adjunctively for resistant lesions Psoriasis TREATMENT OF PSORIASIS WITH TOPICAL AGENTS Topical corticosteroids Topical corticosteroids are the cornerstone of treatment particularly those with limited disease. Topical steroids are safe during pregnancy The use of topical corticosteroids for >12 weeks can be considered if done under the careful supervision of a physician it is recommended that a gradual reduction in the frequency of usage following clinical response be instituted. Intralesional corticosteroids injection can be used for localized nonresponding or very thick lesions (triamcinolone acetonide every 3-4 weeks). Psoriasis TREATMENT OF PSORIASIS WITH TOPICAL AGENTS Vitamin D analogues Calcipotriol (calcipotriene) is a synthetic vitamin D analogue. An important advantage of the vitamin D analogues is their potential to function in a corticosteroid- sparing fashion, so it can be combined with corticosteroids. Psoriasis TREATMENT OF PSORIASIS WITH TOPICAL AGENTS Tazarotene (retinoids) Best used in combination with topical corticosteroids. Tazarotene is a teratogenic retinoid and is pregnancy category X (requires contraceptive use) Psoriasis TREATMENT OF PSORIASIS WITH TOPICAL AGENTS Topical Tacrolimus: A lack of penetration through the thick psoriatic plaque has been reported. This led to the concept of utilizing the topical calcineurin inhibitors in thinner skin areas such as facial and intertriginous psoriasis. They are used as steroid-sparing agents for prolonged use (>4 weeks). To read Phototherapy Psoriasis PHOTOTHERAPY UV light (UVA and UVB) therapy remains an essential therapeutic option for patients with psoriasis. Phototherapy is efficacious, is cost-effective, and generally lacks the systemic immunosuppressive properties of both traditional and biologic systemic therapies. NB-UVB is recommended over broadband ultraviolet B (BB-UVB) monotherapy. Short-term PUVA monotherapy is more efficacious than NB-UVB for treatment of psoriasis in adults (NB-UVB is preferred as safer). Psoriasis PHOTOTHERAPY NB-UVB phototherapy is recommended for pregnant women with generalized plaque psoriasis and guttate psoriasis. Concomitant topical therapy with vitamin D analogues, retinoids, and corticosteroids during NB-UVB phototherapy can be used safely with a potential to improve efficacy Combination therapy with oral retinoids and NB-UVB phototherapy is recommended for appropriate patients with generalized plaque psoriasis who do not respond adequately to monotherapy. Genital shielding is recommended during NB-UVB phototherapy to reduce the risk of genital skin cancer Eye protection with goggles is recommended during NB-UVB phototherapy to reduce the risk of UVB-related ocular toxicity  Traditional Systemic agents Psoriasis TREATMENT OF PSORIASIS WITH TRADITIONAL AGENTS Methotrexate Methotrexate is the most commonly prescribed. Methotrexate inhibits the enzyme dihydrofolate reductase, Doses (oral , intramuscular, subcutaneous) range from 7.5 to 25 mg. It may take up to 4 weeks for a clinical response to occur. Some patients can be gradually tapered off treatment and restarted when the psoriasis recurs. It is important to minimize the total cumulative dose of methotrexate. Psoriasis Treatment of psoriasis with traditional agents Methotrexate All patients treated with methotrexate receive folate supplementation (1-5 mg/d given daily except the day of methotrexate) The major toxicities are myelosuppression, hepatotoxicity, and pulmonary fibrosis. Patients with psoriasis are at higher risk of developing fatty liver disease, fibrosis, and cirrhosis from methotrexate than others. Methotrexate is an abortifacient and a teratogen (category X). Women of childbearing potential who are sexually active and are being treated with methotrexate must use contraception. Psoriasis Treatment of psoriasis with traditional agents Methotrexate It is appropriate for women to wait 3 months after discontinuing methotrexate before attempting to conceive a child. One cycle of spermatogenesis requires 74 days thus it is appropriate for male patients to wait 3 months after discontinuing methotrexate before attempting to conceive a child. The efficacy of methotrexate is lower than TNF-inhibitors. Combination therapy with methotrexate and tumor necrosis factor inhibitors results in improved efficacy over methotrexate monotherapy for the treatment of psoriasis. Methotrexate has been detected in human milk (contraindicated in nursing mothers). Psoriasis TREATMENT OF PSORIASIS WITH NON-BIOLOGICS Apremilat Cyclosporin Oral retinoid Psoriasis Treatment of psoriasis with traditional agents Oral retinoid (acitretin): Indication: FDA approved for adults with severe plaque type psoriasis Pregnancy category X. use adequate contraception for 3 years after discontinuing acitretin. Acitretin no effect on fertility or teratogenicity when men are taking the drug (limited evidence). Mothers receiving acitretin should not breast-feed. Side effects: Hepatotoxicity and Hypertriglyceridemia….. monitor Other agents Second line  Psoriasis Read only TREATMENT OF PSORIASIS WITH NON-BIOLOGICS Not FDA approved: Tofacitinib (oral Janus kinase inhibitor) Dimethyl fumarate Azathioprine/6-thioguanine Hydroxyurea: antimetabolite Leflunomide Mycophenolate mofetil Sulfasalazine. Tacrolimus. Biologic therapy Psoriasis TREATMENT OF PSORIASIS WITH BIOLOGICS Interleukin's TNF inhibitors inhibitors Etanercept Ustekinumab Infliximab Secukinumab Adalimumab Guselkumab Certolizumab  TNF INHIBITORS FOR THE TREATMENT OF PSORIASIS Psoriasis TREATMENT OF PSORIASIS WITH BIOLOGICS TNF alpha nhibitors: They are recommended as a monotherapy treatment option in adult patients with moderate-to-severe plaque psoriasis, plaque psoriasis affecting the nails, other subtypes (pustular or erythrodermic) of moderate-to-severe plaque psoriasis, and plaque psoriasis when associated with significant psoriatic arthritis. ✓Etanercept. ✓Infliximab: chimeric…….combined with methotrexate ✓Adalimumab ✓Certolizumab TB test Psoriasis TREATMENT OF PSORIASIS WITH BIOLOGICS TNF INHIBITORS FOR THE TREATMENT OF PSORIASIS INTERLEUKINS INHIBITORS FOR THE TREATMENT OF PSORIASIS Psoriasis TREATMENT OF PSORIASIS WITH BIOLOGICS It is recommended in with moderate-to-severe plaque psoriasis affecting the palms and soles (plaque-type palmoplantar psoriasis), the nails, the scalp, other subtypes (pustular or erythrodermic) and plaque psoriasis of any severity when associated with significant psoriatic arthritis. Use with caution in HIV, hepatitis b and c Contraindications Untreated hepatitis B infection History of lymphoreticular malignancy Active infection (including TB) or sepsis. Selection of psoriasis treatment Psoriasis GENERAL RECOMMENDATIONS FOR THE TREATMENT OF PSORIASIS Psoriasis TREATMENT OF PATIENTS WITH LIMITED DISEASE Those with limited or mild disease ( less than 5% of the BSA). First line: topical agents, ✓ Topical corticosteroids are a first-line treatment for limited psoriasis as monotherapy or in conjunction with nonsteroidal topical agents. ✓ The vitamin D analogs, calcipotriene, calcipotriol, and calcitriol, are other first-line topical agents. they are often used in combination with topical corticosteroids. ✓ Topical tazarotene, a retinoid, is an additional corticosteroid- sparing agent. ✓ Topical tacrolimus can be considered for intertriginous psoriasis. Psoriasis TREATMENT OF PATIENTS WITH LIMITED DISEASE Targeted phototherapy: Another approach for the treatment of limited disease. This therapy allows for selective targeting of localized psoriatic lesions and resistant areas such as the scalp and skin folds Under certain circumstances, such as an important event, such as an upcoming wedding or a graduation, that consideration be given for the short-term use of systemic agents to gain rapid control. Psoriasis TREATMENT OF PATIENTS WHO REQUIRE MORE THAN TOPICAL THERAPY AND ARE THEREFORE CANDIDATES FOR UV-BASED OR SYSTEMIC THERAPY Patients have more significant disease, typically affecting more than 5% of the BSA (moderate to severe) Some patients may receive this therapies may have less than 5% BSA affected but have psoriasis in vulnerable areas such as the face, genitals, hands and feet (palmoplantar disease), scalp, or intertriginous areas and have disease that adversely affects their quality of life. Psoriasis TREATMENT OF PATIENTS WHO REQUIRE MORE THAN TOPICAL THERAPYAND ARE THEREFORE CANDIDATES FOR UV-BASED OR SYSTEMIC THERAPY NB-UVB is well tolerated, cost effective, and can be used safely in patients with demyelinating disease, in which the use of TNF-alfa- inhibiting biologic agents is contraindicated. If the patient fails to obtain an adequate response after approximately 20 to 30 treatments with NB-UVB given 2 to 3 times weekly, PUVA, traditional systemic agents, or biologic agents should be considered. Psoriasis TREATMENT OF PATIENTS WHO REQUIRE MORE THAN TOPICAL THERAPYAND ARE THEREFORE CANDIDATES FOR UV-BASED OR SYSTEMIC THERAPY Systemic non biologic: Methotrexate would be an option. Acitretin could be considered as a reasonable option for postmenopausal woman either as monotherapy or in combination with NB UVB. Cyclosporine could be used for short-term (not combined with phototherapy), if failure to response to phototherapy combination Psoriasis TREATMENT OF PATIENTS WHO REQUIRE MORE THAN TOPICAL THERAPYAND ARE THEREFORE CANDIDATES FOR UV-BASED OR SYSTEMIC THERAPY Psoriasis and multiple comorbidities. Biologic therapies offer significant advantages to patients with complex medical histories on multiple medications.