Derm STUDY - E3

Lecture 1: Psoriasis

Psoriasis Types & Presentation

• Plaque Psoriasis (Vulgar)

  • Red-violet color, erythema, silver flaking scales

• Psoriatic Arthritis

  • Lesions in conjunction with inflammatory-like arthritis symptoms

    • Distal interphalangeal joins, knees, elbows, wrists, ankles

Psoriasis Diagnosis

• NO skin biopsies

• European Classification System

• BSA and PASI

Psoriasis Treatment

• Mild: <3% BSA

  • 1. Topical

  • 2. Topical + Phototherapy

  • 3. Topical + Systemic

• Mod: 3-10% BSA

  • 1. Systemic Agent ± Topical or Phototherapy

  • 2. Potent Systemic Agent OR 2+ Systemic Agents ± Topical

• Severe: >10% BSA or face, genital, scalp involvement

  • 3. Biologic ± Other

Topical Agents

• Corticosteroids —> (ointment = most potent & occlusive)

  • Low Potency: infants, face, intertriginous areas, thin skin

  • Mild-High Potency: thick plaques, palms

• Retinoids

  • Tazarotene (Tazorac)

    • ADE:

      • Photosensitivity

      • Fetal risk

• Vit D Analog

  • Calcipotriene (Dovonex): D3 analog

• Aryl Hydrocarbon Receptor Agonist

  • Tapinarof (VTAMA)

    • MOA: decrease IL-17

• Salicylic Acid

  • CI: Children

Chronic Use of Corticosteroids

• Drug holiday

• Taper down when lesions improve

• Non-steroid alternative if initial response worsens

Corticosteroids by Potency

• Low

  • Hydrocortisone

• Mild

  • Besonide

• Moderate

  • Triamcinolone

  • Momentasone

• Potent

  • Betamethasone

  • Clobetasol

  • Flucinonide

    • BCF = Be CareFul!

Systemic Non-Biologics

• Methotrexate

  • Pregnancy X

• Apremilast (Otezla) —> safe to combine with others

  • Non-immunosuppressant

  • ADR: Depression

  • CYP3A4 metabolism

• Acitrentin (Soriatane)

  • Non-immunosuppressant

  • ADR:

    • Decreased night vision, dry eyes

    • Sun sensitivity

    • Pregnancy X

  • CYP3A4 metabolism

• Cyclosporin (Gengraf)

  • ADR:

    • Nephrotoxic

    • CBC

    • Electrolyte imbalances (Mg, K)

    • Skin Cancer

Biologics

***DO NOT COMBINE BIOLIGICS WITH EACH OTHER!!!***

• Anti-TNF

  • Adalimumab

  • Etancercept

  • Infliximab

  • Certolizumab

    • SE: opportunistic TB infection, cancer

    • CI: CHF

• Non-TNF

  • IL-12/23

    • Ustekinumab (SQ q12 wk)

      • Indication: plaque psoriasis, psoriatic arthritis, Crohns

      • Less TB risk

  • IL-23

    • Guselkumab (SQ q8 wk)

      • Indication: plaque psoriasis, psoriatic arthritis, Crohns

      • Less TB risk

    • Risankizumab (SQ q12 wk)

      • Indication: plaque psoriasis, psoriatic arthritis, Crohns

  • IL-17

    • Secukinumab (SQ q4 wk)

      • ADR: IBD (Crohns exacerbation), less TB risk

    • Ixekizumab (SQ q4 wk)

      • ADR: IBD (Crohns exacerbation), less TB risk

    • Brodalumab (IL-17R) (SQ q2 wk)

      • ADR: IBD (Crohns exacerbation), less TB risk, Suicidal tendencies

Lecture 2: Skin Conditions (Acne, Urticaria, Rosacea, Atopic Dermatitis)

ACNE (4)

Acne Definition

• Follicular colonization by Cutibacterium acnes

• Inflammatory mediators

Non-Inflammatory (Comedonal) Acne Definition

• Microcomedone-obstructed sebaceous follicle (pore)

• Epidermal cells adhere —> keratinous plug

Non-Inflammatory Acne Treatment (Mild-Moderate)

• 1. Topical Retinoids

  • Adapalene (Differin)

    • SE: dry skin, photosensitivity, fetal harm

  • Tretinoin

    • SE: dry skin, photosensitivity, fetal harm

  • Tazarotene (Tazorac)

    • SE: dry skin, photosensitivity, fetal harm

1. Benzoyl Peroxide

• Keratolytic effects & antibacterial

• Safe for pregnancy

2. Azelaic Acid

• SE: Hypopigmentation

• Safe for pregnancy

Inflammatory Acne Treatment

• Mild-Mod, 1st Line

  • Adapalene + Benzoyl Peroxide

  • Clindamycin + Benzoyl Peroxide

• Topical Antibacterial - DO NOT USE ALONE

  • Topical Erythromycin and Clindamycin

    • SE: increased risk of sunburn

  • Dapsone 5% Topical Gel

• Systemic Antibioitics (+ Benzoyl Peroxide ± Adapalene)

  • Minocycline

    • SE: Photosensitivity

  • Doxycycline

    • CI: Isotretinoin (concomitant use)

    • SE: Photosensitivity

---

• Severe Papulopustular Acne / Cystic Acne

  • [Failed topicals and orals]

    • Oral Isotretinoin Monotherapy - Pregnancy X

      • SE:

        • Photosensitivity

        • Anemia, neutropenia, thrombocytopenia

        • Increased LFTs

        • Thrombosis of blood vessels

        • Optical neuritis

        • Depression, aggressive behavior, suicidal thoughts, psychotic disorder

      • CI: Tetracycline, Vitamin A Supp, St. John’s Wort, Pregnancy

      • Caution: Risk of scarring - 6 mo post therapy

Hormonal-Caused Acne

• Oral Contraceptives (Estrogen/Progesterone)

  • Indication: menstrual related, ovarian disease related acne

• Anti-Androgen Compounds

  • Spironolactone

    • SE: Gynecomastia, erectile dysfunction, hyperkalemia

HIVES (1)

Type 1 Urticaria

• Drug specific IgE

• Urticarial Rash

New Onset Urticaria Treatment

• 1st Gen AH

  • Diphenhydramine

    • SE:

      • Xerostomia (dry mouth)

      • Dizziness, sedation

      • Anticholinergic effects - elderly

Refer to PCP

• Anaphylactic Reaction

  • Difficulty breathing, throat closure

  • Severe angioedema

  • Angioedema in FACE

ROSACEA (1)

Clinical Features of Rosacea

• Flushing

• Edema

Rosacea Treatment

• Facial Erythema (Redness)

  • Vasoactive Alpha-2 Adrenergic Receptor Agonist

    • Topical Brimonidine

    • Topical Oxymetazoline

Lecture 3: Drug-Induced Skin Rxn

HLA-B

Hypersensitivity → rash and skin reactions

• Abacavir

• Allopurinol

• Carbamazepine

CYP2D6

• Tamoxifen

• Fluoxetine

• Atomoxetine

VKORC1 and CYP2C9

Warfarin

• Elevated INR

• Increase bleeding risk

Drug-Induced Lupus

Butterfly rash (cutaneous symptoms), musculoskeletal symptoms

• Hydralazine

• Procainamide

Drug-Induced Acne

• Lithium (dose-related)

Corticosteroid ADRs

• Glaucoma

• Lunacy

• peptic Ulceration

• Cushing’s

• Osteoporosis

• Cataracts

• Opportunistic infections

• Retention of Na+

• Telangiectasia

• Insulin resistance

• Cause muscle weakness/wasting

• grOwth retardation

Lecture 4: Atopic Dermatitis (Eczema)

Pathophysiology of Atopic Dermatitis

• Epidermal barrier dysfunction —> high MW allergens penetrate

Atopic Dermatitis Symptoms

• Pruritis (itching)

• Rash

• Dry

Non-Pharm

• Avoid high pH —> use neutral to low pH soap

Moisturizers

• Occlusive (oily layer) - BEST CHOICE

• Humectant (trap water)

• Emollient (smooth out surface of skin)

Pharmacologic Therapy

1. Topical Corticosteroids - 1st line

• QD-BID

• Control achieved:

  • STOP and just use moisturizers

  • 1-2x/week if frequent flare ups

• ADE: skin atrophy, striae, telanglectasias

2. Topical Calcineurin Inhibitors - 2nd line

• Tacrolimus 0.03% Oint: SHORT-TERM (6 wk), 2+ yo, mod-severe

• Tacrolimus 0.1% Oint: 16+ yo, mod-severe

• Pimecrolimus 1% Cream (lipophilic, preferred)

  • ADE: local skin carcinogenesis (use sun protection)

• Adjunct:

  • UV

  • Oral AH

  • Systemic Corticosteroids

    • SE: HPA axis suppression, Cushing syndrome

  • MTX

    • Pregnancy X

  • Cyclosporine

    • ADR: Nephrotoxic, CBC, electrolyte (Mg, K), skin cancer

  • JAK Inhibitors

    • Ruxolitinib (Opzelura) 1.5% Cream

      • Up to 20% BSA

Lecture 5: Burn Wounds

Wound Classification

• First-Degree: superficial-epidermal

  • Dry, red

• Second-Degree: superficial partial-thickness

  • Moist, red, weeping, blanch with pressure

  • Painful to temp and air

• Third-Degree: full-thickness deep burn

  • Wet or waxy

  • Does NOT blanch with pressure

• Fourth-Degree: devitalized tissue extends into SC tissue, fascia, bone

  • Black, dry, PAINLESS (nerve endings destroyed)

  • Risk of infection

Yamaki Cumulative: DMARDs —> RA Lecture???

Yamaki Cumulative: RA

RA Characterization

• RF

• ACPA → highly specific

RA Treatment

• DMARD - ALL PT

  • Nonbiologics (combine up to 3)

    • Methotrextate (MTX)

      • Weekly PO or SQ

      • Mod/high RA

      • Titrate to 15+mg/week within 4-6 weeks

      • MAX: 30 mg/week

      • SE:

        • Liver dysfunction

        • CBC

        • Decrease folic acid

          • (take folic acid 1 mg PO daily)

          • OR Leucovorin (decreases MTX efficacy- do not take same day)

        • GI upset (take folic acid)

      • CI:

        • PREGNANCY

        • Renal elimination

        • Liver dysfunction

    • Hydroxychloroquine (HCQ)

      • Antimalarial

      • Mild RA

      • Safe in pregnancy

      • SE:

        • Retinal toxicity

          • Eye exam at baseline

      • Sulfasalazine (SSZ)

        • Safe in pregnancy

        • Long onset: 6-12 weeks; Full effect: 23 weeks

        • SE:

          • Hepatitis - LFT

          • Leukopenia - CBC

          • Agranulocytosis

          • Rash

      • Leflunomide (LEF)

        • MOA: inhibit pyrimidine synthesis

        • DDI: liver toxicity with MTC

        • Severe advanced RA

        • SE:

          • Liver toxicity

          • Myelosuppression

          • Lung disease - RARE

          • Peripheral neuropathy - RARE

        • CI:

          • Pregnancy

            • Take Cholestyramine x11 if want to be pregnant

            • Without it —> 2yr to eliminate drug

  • Biologics (do NOT combine)

    • TNF-a

      • Adalimumab - human

      • Infliximab - chimeric

      • Certolizumab - PEGylated Fab fragment

      • Golimumab - human - least freq SC dosing

      • Entanercept - SHORT HALF-LIFE

      • TB, cancer

      • CI: CHF

    • IL-1

      • Anakinra

    • IL-6

      • Tocilizumab

      • Start if treated for TB currently, GI perforation

    • B-cell

      • Rituximab

      • HepB

    • Co-stim

      • Abatacept

      • Start if treated for TB currently, COPD-pneumonia

    • JAK/STAT

      • -nib

      • Thrombosis

      • CI: pregnancy

• NSAIDs or Gucocorticoids - BRIDGING ONLY

• EVALUATE EVERY 3 MONTHS

DMARD Baseline Tests

• CBC

• LFT

• BUN/SCr

• TB [biologic DMARDs]

Treatment failure defined as lack of remission/low disease is following ____ months of DMARD optimal dosing.

3-6 mo

RA Treatment Algorithm

• Low Disease/Mild

  • 1. HCQ

  • 2. Switch to MTX

  • 3. Add biologic DMARD or (JAK/STAT + MTX) - 1st line

    • D/C MTX gradually (taper) when on MTX + biologic or JAKi

  • 3. Triple DMARD (MTX + HCQ + SSZ) - 2nd line

    • D/C SSZ if remission

  • 4. Change different biologic

• Mod/High Disease

  • 1. MTX

  • 2. Maximize MTX dose

  • 3. Add biologic DMARD or (JAK/STAT + MTX) - 1st line

    • D/C MTX gradually (taper) when on MTX + biologic or JAKi

  • 3. Triple DMARD (MTX + HCQ + SSZ) - 2nd line

    • D/C SSZ if remission

  • 4. Change different biologic

Yamaki Cumulative: Lupus

SLE Pathophysiology

• Apoptotic cells → DEFECTIVE CLEARANCE → Nuclear antigen exposure (DNA and RNA)

SLE Lab

• Antinuclear antibody (ANA)

  • Anti-dsDNA antibodies → more specific

SLE Treatment

• Hydroxychloroquine (HCQ) - gold standard

  • Anti-malarial

  • SAFE IN PREGNANCY :)

  • SE:

    • Retinal toxicity

    • EYE EXAM @ BASELINE

  • Dose:

    • Mild: 200-400 mg

      • + Low-dose glucorticoids —> short term (<3 mo)

    • Moderate: 200-400 mg

      • + Low-dose glucorticoids

      • + Steroid-sparing agent (when flare is approved)

    • Mod-to-Severe:

      • + Steroid-sparing

      • + Biologic (belimumab or anifrolumab)

• Belimumab (Benlysta)

  • MOA: B-lymphocyte stimulator

    • Autoimmune antibody-driven

    • Lupus nephritis

• Anifrolumab (Saphnelo)

  • MOA: block INF signaling

    • Inflammation INF-driven

• Glucocorticoids: high dose, IV

• Steroid-Sparing Agents

  • Mycophenolate mofetil

  • Azathioprine

  • Cycophosphamide

  • Rituximab

  • Cyclosporine

SLE Treatment Algorithm

• Mild

  • HCQ

  • + NSAID

  • + Topical Steroid

• Moderate

  • HCQ

  • + Corticosteroids

  • + Steroid-sparing/immunosuppressant

  • or Biologics

• Mod-Severe

  • HCQ

  • + Steroid-sparing/immunosuppressant

  • + Biologic

• Severe

  • High-dose steroid

  • + Steroid-sparing/immunosuppressant

  • + Biologic

Elsaid Cumulative: NSAIDs

COX

• COX 1 - constitutive (always present) - in a lot of organs

• COX 2 - inducible -  increase in inflammation sites

How do nonselective COX inhibitors affect the GI?

COX non-selective inhibitors affect COX1 → inhibit prostaglandins (protect epithelial cells) in stomach  → gastric ulcers

Long-term use of non-selective COX inhibitors → cause _____ and ______. Why?

• High BP/HTN

• Kidney damage

• Why?

  • Prostaglandins = vasodilation

  • NSAIDs block prostaglandins through COX inhibition —> vasoconstriction

COX-2 Selective NSAIDs

• Celecoxib → works at site of inflammation → good for OA

• Meloxicam

• Diclofenac

• Valdecoxib

• Etodolac

• Rofecoxib

• Etoricoxib

• Lumiracoxib

APAP

• COX inhibitor in BRAIN/CNS → does not inhibit COX enzyme at site of inflammation

  • Regulates the local increase of prostaglandin in brain (aka a fever)→ Regulates temperature (CNS!)

  • Does not affect prostaglandin levels in peripheral tissues → CANNOT regulate inflammation

Elsaid Cumulative: DMARDs

DMARDs

• Anti-TNFα

  • Infliximab (chimeric)

    • IV

      • Chimeric has mouse, so harder for body to process, shorter half-life

  • Adalimumab (human)

    • SQ

  • Golimumab (human)

  • Certolizumab Pegol (human > mouse)

    • SQ

---

• Entanercept: soluble decoy TNFα receptor

• Anti-IL-1

  • Anakinra

  • Rilonacept

  • Canakinumab

• Anti-IL-6

  • Tocilizumab

• B Cell

  • Rituximab

    • Transmembrane & soluble receptors

    • STRONG IMMUNOSUPPRESSANT

    • Depletes peripheral B cells

    • Bind to CD20 —> apoptosis, cytotoxicity

• T Cell Costim

  • Abatacept

---

• Oral DMARDs

  • MTX

  • JAK Inhibitors (Tofacitinib, Upadacitinib)

  • Leflunoamide

  • HCQ

  • Azathioprine

  • Cyclosporine

Elsaid Cumulative: Gout

Gout Treatment

• Acute Flares

  • Colchicine

    • SE: Diarrhea, GI, N/V

  • NSAIDs

  • Corticosteroids

  • IL-1 Antagonists

——————————————————————————————————--

• Urate Lowering Therapy

  • Reduce Uric Acid Synthesis

    • Xanthine Oxidase Inhibitors: inhibit xanthine oxidase (reduce uric acid synthesis)

      • Allopurinol —> hypersensitivity

      • Febuxostat

    • Enhance Uric Acid Elimination: inhibit URAT (blocks uric acid reabsorption in blood so it gets excreted in urine more)

      • Probenecid

      • Lesinurad

      • Recombinant Urate Oxidase: urate oxidase converts uric acid to allantoin (more soluble)

        • Rasburicase

          • Fungal

        • Pegloticase

          • Pegylated recombinant uricase —> Procine

What class can reverse MSU crystal deposits (tophi) in tissues?

Recombincant Urate Oxidase / URICASE ENZYME TREATMENT

• Rasburicase

• Pegloticase

What medications are used to reduce hyperuricemia and reduce risk of ARF in TLS patients?

• Allopurinol

• Uricase