Psoriasis Lecture Note

u PSORIASIS G. Mor a t aya , P ha r mD Assoc ia te P rofe ssor We st Coa st Unive r sit y 1 CLINICAL PRESENTATION • Plaque psoriasis (psoriasis vulgaris) –Scaling papules –Silvery white scales • Can develop at site of epidermal trauma (Koebner phenomenon) – Scratch marks – Sunburn – Surgical wounds • Sites include – Elbow, knees, finger/toenails, scalp, gluteal cleft 4 DIAGNOSIS ¡ ¡ ¡ ¡ Contingent on physical exam confirming characteristic lesions Biopsy not required Evaluate for psoriatic arthritis Psoriasis classifications si § Mild to moderate, and moderate to severe § BSA § Psoriasis Area and Severity Index (PASI) 5 BSA 6 T YPES OF PSORIASIS Fy ¡ Plaque Psoriasis ¡ Guttate Psoriasis ¡ Pustular Psoriasis 7 T YPES OF PSORIASIS ¡ Inverse Psoriasis ¡ Erythrodermic Psoriasis ¡ Psoriatic onychodystrophy 8 PATIENT CASE ¡ Chief Complaint (CC) § My scalp has a rash that is very itchy and flaky ¡ History of Present Illness (HPI) §KL is a 29 year old female who presented to the ER while her PCP was away at conference, with localized erythema on her scalp, containing silvery scales. Developed shortly after she bumped her head moving tractor tires at her cross fit class. 9 COURSE OF TREATMENT • Goal of therapy: Complete clearance of psoriatic lesions –Particular attention to special times • Puberty • Summer time • Start of school year • Treatment type determined by presence or absence of psoriatic arthritis with psoriasis 10 NON-PHARMACOLOGIC THERAPY ¡ Stress reduction § Stress Management § Therapy § Meditation ¡ Nonmedicated Moisturizers § Helps maintain skin moisture 11 TOPICAL AGENTS FOR MILD TO MODERATE TREATMENT OF PSORIASIS Treatment Pros Cons Emollients Basic adjunct for all treatment, preferred during pregnancy Minimal relief from monotherapy Keratolytics Reduce hyperkeratosis; enables better penetration of topicals Minimal relief from monotherapy, salicylic adverse effects Topical Corticosteroids Rapid onset of action, effective for control of inflammation and itching, ease of application, effective in facial and skin fold areas, mainstay treatment psoriasis Common flare-up when discontinued, extended use decreases effectiveness, possible adverse effects with continued use, expensive Coal Tar Effective for flaky scalp lesions, efficacy enhanced combined with ultraviolet B (UVB) Messy, strong odor, stains, effective for scalp and mild psoriasis 12 TOPICAL AGENTS FOR MILD TO MODERATE TREATMENT OF PSORIASIS Treatment Pros Cons Anthralin Short-contact anthralin therapy (SCAT) preferred regimen, effective for wide spread, refractory plaques, enhanced with UVB Potential for severe irritation, precautions recommended to area surrounding application site(s), stains Calcipotriene, Calcitriol Roughly as effective as medium to potent corticosteroids, effective monotherapy, well tolerated, less side effects as corticosteroids Slow onset, potential effect for hypercalcemia, skin irritation, Tazarotene (Tazorac®) Extended response, once daily Slow onset, teratogenic, local application, effective on scalp and face, irritation and pruritus used in combination with corticosteroids UVB Effective maintenance therapy, used in combination with agents such as anthralin or coal tar for enhanced efficacy Expensive, office-based therapy, may sunburn, skin cancer 13 Eng CORTICOSTEROIDS CLASSIFICATIONS Classification Strength Example Location for use Class 1 5 Super-potent Clobetasol propionate 0.05% Betamethasone Dipropionate 0.05% Tough, thick and chronic plaques Class 2 Potent Amcinonide 0.1% Fluocinonide 0.05% Tough, thick and chronic plaques Class 3 Upper Middle Fluticasone propionate 0.005% ointment Mometasone furoate 0.1% Tough, thick and chronic plaques Class 4 Middle Betamethasone valerate 0.12% Tough, thick and chronic plaques Class 5 Lower Middle Fluticasone propionate 0.05% cream Triamcinolone acetonide 0.1% Face, thin skin, and skin folds Class 6 Mild Desonide 0.05% Fluocinonide acetonide 0.01% Face, thin skin, and skin folds Class 7 Least Potent Hydrocortisone 0.5%, 1%, 2%, or 2.5% Face, thin skin, and skin folds14 s s TOPICAL CORTICOSTEROIDS ¡ Usual potency from highest to weakest Eat § Ointment > creams > lotions > solutions > gels > sprays ¡ High-risk for topical steroid overuse § Seen with use > 2 weeks § Skin thinning § Pigmentation changes 15 SEVERE PSORIASAS TREATMENT AGENTS Treatment Pros Cons UVA and psoralen (PUVA) Very effective Time consuming, expensive, office-based therapy, photoaging, skin cancer Acitretin (Soriatane) Efficacy enhanced with PUVA or UVB, Teratogenic, contraindicated with liver or renal impairment Methotrexate Effective for both skin lesions and arthritis as well as psoriatic nail disease Hepatotoxicity, drug interactions, pregnancy category X, bone marrow toxicity 16 SEVERE PSORIASAS TREATMENT AGENTS Treatment Pros Cons Cyclosporine Increasing role in rotational therapy to induce remissions, produces immunosuppressive response Serious adverse effects include hypertension and nephrotoxicity, increased risk of malignancies, skin cancer, phototoxic, combination therapy limitations Immunomodulators Targeted therapy, effective Expensive, difficult for psoriatic arthritis and skin insurance processes, lesions, maintains remissions lack long term safety data, increased risk for serious infections 17 PHOTOTHERAPY § Ultraviolet light B (UVB) § Narrow-band UVB > Broad-band UVB § Used when extensive or unresponsive to topical tx § Adverse effects § Burning, itching, stinging § Lesional blistering § Psoralen plus ultraviolet light A (PUVA) § 8-methoxypsoralen § Ability to penetrate skin to effect § Dendritic cells, fibroblasts, and inflammatory cell § Adverse effects § Potential for skin cancer 18 SYSTEMIC THERAPY ¡ Methotrexate § Competitive inhibitor for dihydrofolate reductase § Dosing § 7.5mg – 25mg once a week by mouth § Adverse effects § Nausea, abdominal discomfort, fatigue § Hepatotoxicity § Hematologic toxicity § Pregnancy category X 19 SYSTEMIC THERAPY ¡ Cyclosporine § Calcineurin inhibitor § MOA: § Inhibits T-cell activation, thereby producing an immunosuppressive response § Dosing: § Initial dose of 2.5-3mg/kg in two divided doses by mouth § Titrate in increments of 0.5mg/kg/day § Maximum dose for psoriasis 5mg/kg/day § Adverse effects § Hypertension, nephrotoxicity 20 SYSTEMIC THERAPY ¡ Acitretin (Soriatane®) can'tdrinkTwist § Retinoid § Dosing: 25-50 mg by mouth daily with main meal § Adverse effects: § BBW – Hepatotoxicity, Pregnancy § Pregnancy category X 21 BIOLOGIC THERAPY ¡ TNFα Inhibitors § Entanercept (Enbrel®), Adalimumab (Humira®), Infliximab (Remicade®), Golimumab (Simponi®) § Side effects: § Injection site reactions § Drug induced lupus § Hepatotoxicity ¡ Interleukin-12/23 Inhibitor § Ustekinumab (Stelera®) § Side effects: § Infection, headache, fatigue, diarrhea § Pregnancy Category B § Approved for the treatment of psoriasis in adults 18 years or older with moderate-to-severe plaque psoriasis 22 BIOLOGIC THERAPY § Interleukin-17A Receptor Antagonist § Secukinumab (Cosentyx®) § § § Dosing: 300mg SubQ once weekly at at weeks 0, 1, 2, 3 and 4 followed by 300mg every 4 weeks. ½ the dose for psoriatic arthritis Adverse effects: § Diarrhea, URTIs § Warnings: § Screen for latent TB § Exacerbation of Crohn’s disease § Latex hypersensitivity 23 BIOLOGIC THERAPY § Interleukin-23 Inhibitor § § § Risankizumab (Skyrizi®) Dosing: 300mg Prefilled syringe and auto-injector: 150 mg at weeks 0, 4, and then every 12 weeks thereafter. Adverse effects: § Infection, URTIs, § Warnings: § Prior to initiation, certain assessments (clinical and laboratory) are required with documentation and ensure age-appropriate vaccinations are up to date. In general, live vaccines should not be administered within 4 weeks prior to starting therapy . Refer to institutional protocols for vaccination and monitoring requirements prior to initiating therapy 24 NOT A BIOLOGIC THERAPY ¡ Phosphodiesterase-4 Enzyme Inhibitor § Apremilast (Otezla®) § Dosing: 10mg daily by mouth in the morning § Titrate daily by 10mg per day to 30mg twice per day § Adverse effects: § Diarrhea, N/V, headache § Warnings: § Depression and suicidal ideation, weight loss. 25 Exam BIOSIMILARS so Remicade • Inflectra ® • Erelzi so ® Enbrelentercepti • Amjevita ®M Humid 26 BIOSIMILARS ¡ American College of Rheumatology White Paper on Biosimilars: The American College of Rheumatology (ACR) published a white paper that reviews the scientific, clinical, economic, and prescribing issues related to use of biosimilars. § A "biosimilar" is a biologic product that is highly similar to an approved reference (or originator) biologic product and has no clinically meaningful differences in efficacy, adverse effects, or immunogenicity compared to the reference product. § Based on the outcomes of rigorous regulatory requirements, the ACR white paper asserts that patients and healthcare providers should have confidence that an approved biosimilar should produce clinical outcomes comparable to those achieved with its reference product. § The paper encourages healthcare providers to incorporate biosimilars into their practices where appropriate with the goal of continued delivery of high-quality health care at lower cost to individual patients. 27 FUTURE PROGRESS ¡ Certolizumab-pegol, abatacept ¡ SCH90222, CNTO1959, CEP-37247, ixekizumab 28 PSORIATIC ARTHRITIS ASSESSMENT 29 MILD TO MODERATE TREATMENT ALGORITHM Topical Agent(s) If inadequate or ineffective Topical Agent(s) + phototherapy If inadequate or ineffective Plus moisturizers ad libitum. Continue if controlled. Step down to lowest doses or potencies that maintain control of disease. Topical Agent(s) + Systemic Agents 30 MODERATE TO SEVERE TREATMENT ALGORITHM Systemic Agent +/- Topical Agent or Phototherapy Consider BRM if comorbidities exist If inadequate or ineffective More potent systemic agent or 2 or more systemic agents in rotation +/- topical agent Plus moisturizers ad libitum. Continue if controlled. Step down to lowest doses or potencies that maintain control of disease. If inadequate or ineffective Biological response modifier (BRM) +/- other agents 31 SUBJECTIVE FINDINGS ¡ Chief Complaint § “Itchy and flaky rash on the scalp” ¡ History of Present Illness § Patient noticed appearance of what she calls a rash on her scalp 4 days ago. Developed shortly after she bumped her head moving tractor tires at her cross fit class. ¡ Past Medical History § Health in good standings, no previous surgical history, no known drug allergies. ¡ Medication History: • 25g supplemental protein shake daily ¡ Social Histor y § Patient is a non-smoker and occasional drinker. She exercises regularly (3 times a week) and maintains a good diet which includes lots of vegetables. Patient is married with no children. ¡ Family Histor y § Both of patient s parents are deceased. Patient s father had a past history of lupus and died due to prostate cancer. Mother had a history of alopecia and died of old age. ¡ Review of Symptoms: § Patient is experiencing itching on the scalp for 4 days after recent minor head trauma, denies any joint pains or aches. Patient fits clinical presentation of plaque psoriasis 32 Ffs OBJECTIVE FINDINGS Topiary ¡ V it a l S igns: ¡ L a b Te s t Re s u l t s : § RBC: 5.1 x 10 6 /uL (normal: 4.5-5.5 x 10 6 /uL) § Blood Pressure- 120/72 § Normal : § Height:5 1 § WBC: 5.9 x 10 3 /uL (normal: 4.5-10 /uL ) § Weight: 95 lbs § Hgb: 14.5 g/dl (normal: 12.0 – 15.5 g/dl) § Temperature-98.0 F § Hct: 42% (normal: 34.9-44.5%) § Pulse-75 bpm § MCV: 92.0 (normal: 80-100) ¡ P hysic a l Exa mina t ion: § MCHC: 34.5 g/dl (normal: 31 – 37g/dl) § Heads, Ears, Eyes, Nose and Throat § PLT: 200,000 (normal: 100,000 – 450,000) (HEENT):normal § DIFFERENTIAL § Pupils are equal and reactive to § Sodium: 140 mEq/l (normal: 135-147 mEq/l ) light § Potassium: 3.9 mEq/l (normal: 3.5-5.2 mEq/l § Lungs: normal ) § Cardiovascular: normal § Chloride: 103 mEq/l (normal: 95-107 mEq/l) § Normal EKG § CO2: 27 mEq/l (normal: 23-30 mEq/l) § Chest X-ray: normal § BUN: 10 mg/dl (normal: 7-20 mg/dl) § Nuero: normal § SCr: 1.1 mEq/dl (normal: 0.5-1.4 mEq/dl) § Abdominal § Fasting Glucose: 91 mEq/dl (normal: 60-110 mEq/dl ) § Non-tender, or distension § Uric Acid: 5.0 mg/dl (normal: 2.0-8.0 mg/dl) ¡ D ia gnost ic Te st s: § CK: 117 IU/L( normal: 8-150 IU/L) § hCG + 4 pregnant NÉE § Cholesterol: 185 mg/dl (normal: 120-200 mg/dl) ¡ R i s k Fa c to r s : 33