Don’t You, Forget

About Me…The Autoimmune Conundrum

Terri Nagy, MPAS, PA-C

tnagy@dermatologypartners.com

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Topics

Alopecia

Psoriasis

VitiligoHidradenitis Suppurativa

Atopic Dermatitis

Hair Loss

Alopecia

Hair cycle

Anagen

• Growth phase

• Can last 2-6 years

• 80-90%

Catagen

• Regression and Apoptosis

• Some hair loss is early entry into this phase

• Last 2 weeks

• 1%

Telogen

• Resting phase

• Last 10 days

• 1-15%

Androgenetic

Alopecia

Trichotillomania

Self inflicted hair loss

Telogen Effluvium

Chronic Inflammation

Common thread in all types

• Including Androgenic Alopecia

• Micro-inflammation

1

Present at the follicle

2

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

Each follicle has a stem cell reservoir

01Immune Privilege

• One of few sites in the body

• Prevents the induction of both innate and adaptive immune responses

02

Receptors – balance of ALL determines

growth Retinoids

Micro-Inflammation

• Leads to overproduction of IL-1, TNF-a

• TGF-b is over produced

• Signals growth arrest

• ROS

• UV light, pollutants, stress, aging, smoking, bacteria, fungi, etc

• Psycho-emotional stress

• Occurs over time

• Interferes with normal cycling and stem cell renewal

• Induces Catagen

Thyroid Disease

Atopic Disease

Metabolic Syndrome

H. Pylori Infection

Lupus Erythematous

Iron Deficiency

Anemia

Vitamin D Deficiency

Psychiatric Diseases

Autoimmune disorders

Treatment

IL steroid injections (2.5 – 5mg/cc)

Topical Class 1 Steroids (Clobetasol) foams

Biotin 2500-3000 mcg daily

Rogaine 5% foam

Others…

Ketoconazole shampoo

Zyrtec

MVI, Vit D3

Elidel

On the

horizon

• 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

by cytokines leading to the blocking of pro-

inflammatory gene transcription.

• Block several ILs at once

• Assessment: SALT score

• Involved scalp surface area (SSA)

Potential side effects of JAK

Known from Xelganz

(tofactinib)

TB and Hepatitis screening required

Cancer Elevated lipids

Kidney and liver dysfunction

Anemia*Feb. 2019 - PE

and death

Vitiligo

Vitiligo

• “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

Cause ~ not completely understood

0.5-2% of population

• Not statistical – more females present

More females than males?

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

Treatments??

• Depigmentation with hydroquinone 20% -

Monobenzone – only FDA approved

• TCS

• Tacrolimus 0.3-1% ointment

• Vitamin supplements? (C, Folic Acid, B12)

• Surgical: punch minigrafting

• Melgain??

• Laser – Xtrac

• JAK Inhibitors

Psoriasis

And this funny man…

8 Million

Americans

Plaque Psoriasis

Most common

85-90%

Genetics

Alcohol

Cigarettes

MedicationSkin injury

Trauma

Infections

Stress

Triggers

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

Comorbidities

and Psoriasis

Cardiovascular and metabolic disease

Cancer – lymphoma

Obesity

Ocular inflammation

IBD - UC/Crohns

Psoriatic Arthritis – 30%

Psychological – Depression/anxiety

Terminology

• BSA – Body Surface Area

• Rules of nine

• Palm – 1%

• IGA – Investigator’s Global

Assessment (studies)

• Induration, erythema, scale

• 0-4

• PASI – Psoriasis Area and Severity

Index (studies)

• Divide body into four sections

• Induration, erythema, scale

• % of area covered

• 0-4

• Absolute: 0-72

Psychological Impact

• NPF QOL study

• 5604 patients

• Embarrassed?

• Angry/frustrated?

• Helpless?

• Disfigured/unsightly?

• Self conscious?

88%

PSO impacts overall

emotional wellbeing

82%

PSO impacts ability to

enjoy life

7 Million

Americans

Treatments

• Topical corticosteroids/calcipotriene

• New: halobetasol and tazarotene lotion

• (Duobrii)

• MTX

• 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

Adalimumab

Certolizumab

pegol

Ustekinumab

Guselkumab

Ixekizumab

Secukinumab

*Brodalumab*

Apremilast

JAK

Inhibitors

Hidradenitis Suppurativa

Celebrities????

What is it?

Follicular disease in the areas of apocrine glands

Genetics, hormones, infections, smoking, obesity, irritants

Most commonly Staph aureus

Pathophysiology similar to acne – but chronically inflammatory

And…

Comorbidities• Obesity

• Metabolic syndrome

• Depression/anxiety

• Arthritis

• IBD

• PCOS

• CAD, anemia

Complications• Chronic pain

• Fistulae

• Lymphedema

• SSC

Treatments

• Antibacterial cleansers

• Weight reduction

• Smoking Cessation

• Lasers and surgery

• Antibiotics, IL steroids, spironolactone, finasteride, isotretinoin

Humira

(Adalimumab)

12 years of age and up

Mod/severe HS

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

Chronic contact dermatitis

7,450,560

Atopic

dermatitis

2,912,597*

Chronic

contact

unspecified

dermatitis

6,441,403*

Chronic

allergic

dermatitis

487,000*

Chronic

irritant

dermatitis

27,000*

Acute

allergic

dermatitis

1,790,000*

*Source: PDDA, patients diagnosed and treated.

Eczema: A Prevalent Condition

ATOPIC

DERMATITIS

Definition

Pruritic disease

01Usually starts in infancy

02Signs and symptoms

• Pruritus

• Excoriations

• Xerosis

• lichenification

03

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

Comorbidities

and AD?

Asthma

Seasonal allergies

• Cardiovascular disease

• Diabetes

• Obesity

• Anxiety/depression

• Autoimmune disorders

But what about:

The more

severe the AD

– the higher

the risk

Immune/

Inflammatory

Process

• PDE4 inhibitor

• PDE4 – phosphodiesterase 4 – enzyme involved in the production of inflammatory mediators in immune cells

• Only indication: atopic dermatitis

• EXPENSIVE

Eucrisa

• Monoclonal antibody

• 12 and older

• Elevated IgE

Dupixent

JAK Inhibitors

JAK Inhibitors

Topical and oral meds

01None currently approved

02Ruxolitinib – applied BID in study – 71.6% improvement at 4 weeks

• Eczema Area and Severity Index (EASI)

• Out performed TMC

03

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?