1. Eczema and psoriasis 20 minute update
Melinda F. Greenfield, DO
Advanced Dermatology and Cosmetic Surgery
Ponte Vedra Beach, FL

2. Disclosures
Speaker’s board for Celgene

3. Eczema aka atopic dermatitis
Group of diseases resulting in erythematous, scaly rashes on various parts of the body with the potential for systemic involvement as well
Pruritus is common
Common associations with food allergies, asthma and general atopy
A number of genes have been associated with eczema, one of which is fillagrin, but the fillagrin defects or mutations are not seen in early onset disease, these occur later in life following chronic infections and inflammationI
Genome-wide studies found three new genetic variants associated with eczema: OVOL1, ACTL9 and IL4-KIF3A

6. Hygiene hypothesis aka biome depletion hypothesis
Hygiene hypothesis was formulated in 1989 by an epidemiologist- Dr. Strachan
He reported an inverse relationship between family size and the development of atopic disorders
Proposed lower exposure to infections in early childhood and loss of contact with dirty older siblings led to less exposure to infections, helminths, etc.
Other researchers have suggested that declining microbial exposure, overuse of antibiotics, antibacterial agents, and a more urban style of living have caused the sharp rise in atopic disorders

7. Treatment of eczema Emollients Avoid triggers Topical steroids
Antihistamines
Topical immune modulators (Elidel, Protopic)
Crisaborole (Eucrisa) ointment recently received FDA approval to treat mild to moderate eczema in patients aged 2 years and older
Dupilumab(Dupixent) injection-just FDA approved (March 2017)- interleukin-4 alpha antagonist - for adults with moderate to severe atopic dermatitis
Probiotics

8. Eucrisa Topical phosphodiesterase 4 (PDE4) inhibitor
Recently FDA approved
Indicated for mild to moderate atopic dermatitis in patients 2 years of age and older

9. CAMP
Cyclic adenosine monophosphate (cAMP) is the principal secondary messenger responsible for immune response regulation
PDE4 is the prominent enzyme that degrades cAMP in many immune cells including: eosinophils, neutrophils, macrophages, T cells, monocytes and keratinocytes
Inhibitors of PDE4 can prolong or enhance the effects of cAMP, resulting in suppression of both Th1 and Th2 immune response
Due to these immune modulating effects, PDE4 inhibitors are currently under investigation for a variety of conditions including asthma, chronic obstructive pulmonary disease, atopic dermatitis, psoriasis, and psoriatic arthritis.

10. PDE4 inhibitors work here

11. Dupixent (dupilumab)
The interleukin 4 and 13 pathways have been implicated in the pathophysiology of allergic diseases, specifically asthma and atopic dermatitis
Dupilumab is an interleukin-4 receptor alpha antagonist and is a human monoclonal antibody of the IgG4 subclass that binds to the IL-4R alpha subunit and inhibits IL-4 and IL-13 signaling
In 2013, mid-stage data was presented at the American Thoracic Society meeting and published in the NEJM demonstrating an 87% (placebo: 67%) reduction in asthma exacerbations in patients with moderate-to-severe allergic asthma.
In an atopic dermatitis study, 85% of patients improved their symptoms by at least 50% within twelve weeks versus 35% in the placebo group

12. Probiotics
2012 Journal of Allergy and Clinical Immunology, : Infants whose mothers took probiotics during pregnancy and breastfeeding were less likely to develop eczema
23 randomized, placebo-controlled studies examining the effects of probiotics on the development of eczema and food allergies- 60% of these studies show a favorable outcome during first year of life

13. FEBRUARY
2017
DERMATOLOGY WORLD

14. MICROBIOME Certain diseases carry with them certain types of bacteria
Healthy skin shows a balance of bacteria
Dysbiosis causes an imbalance and results in a pro-inflammatory state
This leads to dysregulation of the immune system
NIH is currently evaluating trial of skin autologous microbiome transplant to decrease S. aureus colonization
‘The option of rebalancing and rediversifying the skin microbiome, instead of eliminating pathogens randomly will add to the arsenal of treating skin diseases’

15. REPRESENT THE FUTURE OF MEDICINE??
COULD THIS GUY
REPRESENT THE FUTURE OF MEDICINE??

16. psoriasis
Psoriasis is a complex, chronic, multifactorial, inflammatory disease that involves hyperproliferation of the keratinocytes in the epidermis, with an increase in the epidermal cell turnover rate
Environmental, genetic and immunologic factors all play a role

17. Plaque psoriasis
Plaque psoriasis is the most common form of the disease and appears as raised, red patches covered with a silvery white buildup of dead skin cells
These plaques most often appear on the scalp, knees, elbows and lower back
They are often pruritic, can be painful, and can fissure and bleed

18. guttate psoriasis
Guttate psoriasis is a form of psoriasis that appears as small, diffuse lesions
Often starts in childhood or young adulthood, and can be triggered by a strep infection
This is the second-most common type of psoriasis
10 percent of patients with psoriasis have this form

19. inverse psoriasis
Inverse psoriasis appears as erythematous lesions in body folds, such as behind the knee, under the arm or in the groin
It may appear smooth and shiny
It is often mistaken for candida or tinea infections or other forms of intertrigo

20. Pustular psoriasis
Pustular psoriasis is characterized by psoriatic lesions containing pustules
The pus consists of white blood cells
It is not an infection, nor is it contagious
Pustular psoriasis can occur on any part of the body, but occurs most often on the hands or feet

21. Erythrodermic psoriasis
A severe form of psoriasis that leads to widespread, erythema over most of the body
It can cause severe pruritus and pain, and can evolve to desquamation of the skin
It is rare, seen in less than 3% psoriatic patients
Can be triggered by abrupt cessation of treatment, sunburn, infection, use of systemic steroids, stress, alcohol

22. Psoriatic arthritis
Over 30% of people with psoriasis will eventually develop psoriatic arthritis
Often misdiagnosed
Commonly seen in the DIP joint in the hands and often has nail involvement
Spondylitis is a common form
Patients with PSA also have higher rates of HTN, hypercholesterolemia, heart disease and DM

23. Treatments Topical corticosteroids Coal tar 0.5-33%
Keratolytic agents (eg, anthralin, urea, lactic acid)-Use of these medications may facilitate more direct steroid contact with the skin
Vitamin D analogs (eg, calcitriol ointment, calcipotriene, calcipotriene and betamethasone topical ointment)
Topical retinoids (eg, tazarotene)
Antimetabolites (eg, methotrexate)
Immunomodulators (eg, tacrolimus topical 0.1%, cyclosporine, alefacept, ustekinuma
TNF inhibitors (eg, infliximab, etanercept, adalimumab)
Phosphodiesterase-4 inhibitors (eg, apremilast)
IL-12/23 inhibitors (Ustekinumab-Stelara)
Interleukin-17 inhibitors (eg, ustekinumab, secukinumab, ixekizumab, brodalumab)

24. TNF- Inhibitors
The pharmacological class of TNF alpha inhibitors includes etanercept (Enbrel) infliximab (Remicade) and adalimumab (HUMIRA),
These drugs share mechanisms of action and therapeutic uses: rheumatologic diseases, IBD and psoriasis
The most important aspect of these drugs is that therapy is a targeted approach, allowing to avoid a wide range of side effects associated with treatment with nonspecific immunosuppressive agents

25. Phosphodiesterase 4 inhibitors
Apremilast-Otezla
FDA approved 2014 for treatment of psoriatic arthritis and moderate to severe psoriasis
Apremilast is an inhibitor of PDE4,[ an enzyme that breaks down cyclic adenosine monophosphate (cAMP)
In inflammatory cells, PDE4 is the dominant enzyme responsible for this reaction
The resulting increase in cAMP levels down-regulates expression of a number of the pro-inflammatory factors tumor necrosis factor alpha (TNFα), interleukin 17, interleukin 23, and many others, and up-regulates the anti-inflammatory interleukin 10

26. IL-12/23 inhibitor Ustekinumab-Stelara
Ustekinumab is a human IgG1κ monoclonal antibody that binds with specificity to the p40 protein subunit used by both the IL-12 and IL-23 cytokines
IL-12 and IL-23 are naturally occurring cytokines that are involved in inflammatory and immune responses

27. Interleukin-17 inhibitors
The IL-17 family is a group of molecules involved in host defense against pathogens and inflammatory processes
Broadalumab(Siliq), secukinumab(Cosentyx), and ixekizumab(Taltz) all work by interfering with the IL-17 pathway

28. WHAT DOES THE FUTURE HOLD?
Researchers have developed a novel cell-based strategy for the treatment of psoriasis. Their synthetic biology–based gene circuits “can autonomously couple the detection of disease biomarkers with the production of therapeutic proteins,” according to a study published December 16, 2015 in Science Translational Medicine
In the future, dermatologists could implant engineered autologous cells containing the cytokine converter and the implanted device takes full control of the therapy
In 2016, researchers have discovered ten new genetic markers for eczema, bringing the total up to 31 that have been discovered

29. -MELINDA F. GREENFIELD, DO
“ THANK YOU”
-MELINDA F. GREENFIELD, DO