Don’t You, Forget About Me… The Autoimmune Conundrum Terri Nagy, MPAS, PA-C [email protected] 1 in 4 Alopecia Atopic Psoriasis Dermatitis Topics Hidradenitis Vitiligo Suppurativa Hair Loss Alopecia Hair cycle Anagen Catagen Telogen • Growth phase • Regression and • Resting phase • Can last 2-6 years Apoptosis • Last 10 days • 80-90% • Some hair loss is early • 1-15% entry into this phase • Last 2 weeks • 1% Androgenetic Alopecia Trichotillomania Self inflicted hair loss Telogen Effluvium Chronic Inflammation 1 2 Common thread in all types Present at the follicle • Including Androgenic Alopecia • Micro-inflammation Anagen • Initiated by Dermal Papilla Cells (DPC) • Secrete mediators which regulate stem cells • Influence growth • Anagen Stimulating Factors • IGF-1 • bFGF • VEGF Catagen • Decrease in anagen-maintaining factors • Increase in Pro-apoptotic cytokines • TGF-b • IL-1 • TNF-a Stem Cells and Immune Privilege 01 02 Each follicle has a stem cell Immune Privilege reservoir • One of few sites in the body • Prevents the induction of both innate and adaptive immune responses Receptors – balance of ALL determines growth Retinoids Micro-Inflammation • Leads to overproduction of IL-1, • Occurs over time TNF-a • Interferes with normal cycling and • TGF-b is over produced stem cell renewal • Signals growth arrest • ROS • Induces Catagen • UV light, pollutants, stress, aging, smoking, bacteria, fungi, etc • Psycho-emotional stress Thyroid Disease Atopic Disease Metabolic Syndrome H. Pylori Infection Lupus Erythematous Iron Deficiency Anemia Vitamin D Deficiency Psychiatric Diseases Autoimmune disorders IL steroid injections (2.5 – 5mg/cc) Topical Class 1 Steroids (Clobetasol) foams Treatment Biotin 2500-3000 mcg daily Rogaine 5% foam Ketoconazole shampoo Zyrtec Others… MVI, Vit D3 Elidel • JAK inhibitors • Oral meds • PF-06651600 (a JAK3 inhibitor) and PF-06700841 (a JAK1/tyrosine kinase 2 inhibitor) • Inhibit enzymes (Janus Kinase) which are activated On the by cytokines leading to the blocking of pro- inflammatory gene transcription. horizon • Block several ILs at once • Assessment: SALT score • Involved scalp surface area (SSA) Potential side effects of JAK Known from TB and Hepatitis Xelganz screening Cancer Elevated lipids (tofactinib) required Kidney and liver *Feb. 2019 - PE Anemia dysfunction and death Vitiligo Cause ~ not completely understood • “Autoimmune disorder” • Absence of functional or recognizable melanocytes • Inflammatory process • High levels of TNFa, IL-1 and 17 • Vitamin deficiency?? • Maybe – an over reactive response to protect against MM Vitiligo 0.5-2% of population More females than males? • Not statistical – more females present Average age of onset: 20 years old 1873 Medical records reviewed 20% had at least one comorbid diagnosis Alopecia areata Addison disease Autoimmune gastritis IBD Pernicious anemia Psoriasis RA Systemic lupus 31 fold increase in frequency of alopecia areata than general population Also found association with: Guillain-Barre, myasthenia gravis, linear morphea, discoid lupus and Sjogren syndrome • Depigmentation with hydroquinone 20% - Monobenzone – only FDA approved • TCS • Tacrolimus 0.3-1% ointment • Vitamin supplements? (C, Folic Acid, B12) Treatments?? • Surgical: punch minigrafting • Melgain?? • Laser – Xtrac • JAK Inhibitors Psoriasis And this funny man… 8 Million Americans Plaque Psoriasis Most common 85-90% Triggers Genetics Alcohol Infections Cigarettes Skin injury Medication Stress Trauma What happens? • Initial event: trauma, illness, etc • Starts acute inflammatory process – but doesn’t stop there - genetics • T cells get involved – cause release of cytokines – leads to chronic inflammation • Psoriatic plaques create new blood vessels – allows cytokines to travel throughout body – causing inflammatory problems far beyond the skin Cardiovascular and metabolic disease Cancer – lymphoma Obesity Comorbidities Ocular inflammation and Psoriasis IBD - UC/Crohns Psoriatic Arthritis – 30% Psychological – Depression/anxiety Terminology • BSA – Body Surface Area • PASI – Psoriasis Area and Severity • Rules of nine Index (studies) • Palm – 1% • Divide body into four sections • IGA – Investigator’s Global • Induration, erythema, scale Assessment (studies) • % of area covered • Induration, erythema, scale • 0-4 • 0-4 • Absolute: 0-72 Psychological Impact • NPF QOL study • Embarrassed? • 5604 patients • Angry/frustrated? • Helpless? • Disfigured/unsightly? • Self conscious? 88%82% PSOPSO impacts impacts ability overall to emotionalenjoy wellbeing life 7 Million Americans • Topical corticosteroids/calcipotriene • New: halobetasol and tazarotene lotion • (Duobrii) • MTX Treatments • Biologics • Only 36% with mod/severe psoriasis • Goal of Treatment: NPF <1% BSA at 3 months Lesson on names… • - mab = monoclonal antibodies • -ki (n) = interleukin • The substem proceeding –mab: indicates from which animal the antibody was obtained • Mouse: -omab • Humanized: -zumab • Human and mouse • Human: -umab Etanercept Ustekinumab Adalimumab Guselkumab JAK Certolizumab Inhibitors pegol Ixekizumab Apremilast Secukinumab *Brodalumab* Hidradenitis Suppurativa Celebrities???? Follicular disease in the areas of apocrine glands Genetics, hormones, infections, smoking, obesity, irritants What is it? Most commonly Staph aureus Pathophysiology similar to acne – but chronically inflammatory And… Comorbidities Complications • Obesity • Chronic pain • Metabolic syndrome • Fistulae • Depression/anxiety • Lymphedema • Arthritis • SSC • IBD • PCOS • CAD, anemia Treatments • Antibacterial cleansers • Weight reduction • Smoking Cessation • Lasers and surgery • Antibiotics, IL steroids, spironolactone, finasteride, isotretinoin 12 years of age and up Humira Mod/severe HS (Adalimumab) Two 80 mg pens on day 1; One 80 mg pen on day 15; then 40 mg every two weeks starting on day 29 Atopic Dermatitis And the list goes on….. Eczema: A Prevalent Condition Eczema Atopic Chronic Chronic Chronic Acute dermatitis contact irritant allergic allergic 2,912,597* unspecified dermatitis dermatitis dermatitis dermatitis 27,000* 487,000* 1,790,000* 6,441,403* Chronic contact dermatitis 7,450,560 *Source: PDDA, patients diagnosed and treated. ATOPIC DERMATITIS Definition 01 02 03 Pruritic disease Usually starts in Signs and symptoms infancy • Pruritus • Excoriations • Xerosis • lichenification LICHENIFICATION CAUSES ‘AD’ Treatment Avoid irritants/allergens/causative agents Moisturize – to restore barrier Topical steroids Oral steroids/antibiotics Dr. Aron’s Regimen for AD • Compounded product • Betamethasone • Mupirocin • Vanicream • Apply up to six times daily for first week, decreasing there after Asthma Seasonal allergies Comorbidities But what about: and AD? • Cardiovascular disease The more • Diabetes severe the AD – the higher • Obesity the risk • Anxiety/depression • Autoimmune disorders Eucrisa • PDE4 inhibitor • PDE4 – phosphodiesterase 4 – enzyme involved in the production of inflammatory mediators in immune cells • Only indication: atopic dermatitis Immune/ • EXPENSIVE Inflammatory Dupixent Process • Monoclonal antibody • 12 and older • Elevated IgE JAK Inhibitors JAK Inhibitors 01 02 03 Topical and oral meds None currently approved Ruxolitinib – applied BID in study – 71.6% improvement at 4 weeks • Eczema Area and Severity Index (EASI) • Out performed TMC Theme? • Genetics • Inflammation • Acute inflammation starts process • Genetics steps in • Chronic inflammation results • Systemic Dietary Guidelines • Hypocaloric diet and weight reduction in overweight/obese individuals • Smaller portions rather than fad diets/surgery • Healthy choices • Mediterranean diet – PSO • Paleo - HS • Gluten free diet for patients who test positive for serologic markers of gluten sensitivity • Oral Vit D supplement Still Another Common Denominator… Quality of Life Tools Do You Ask?.