3/7/2018

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Erin Hennessey DNP, APRN, FNP-C

Women’s Health and Plastic Surgery /Cosmetic Laser Practitioner

Most dermatology medications have become exorbitantly priced. My goal is to give patients generic or alternative, evidence based options for the treatment of their conditions.

Acne vulgaris is the most common skin disease in the United States. It affects upwards of an estimated 80% of Americans at some time during their lives.

Twenty percent have severe acne, which can result in permanent physical and mental scarring.

The Global Burden of Disease (GBD) 2010 project measured disease burden using disability-adjusted life years (DALYs) metrics(Hay 2014).

Of the 15 dermatologic conditions analyzed in the GBD 2010 study, acne vulgaris was the skin disease with the second highest percentage of total 2010 DALYs (second to fungal skin disorders) (Hay 2014).

Thus, the global burden of acne is very high (Hay 2014). A recent report, however, has demonstrated that the limited number of reviews and protocols published in the Cochrane Database of Systematic Reviews(CDSR) does not reflect disease disability estimates for acne and that this topic is underrepresented

Other skin diseases that had high levels of burden include eczema and psoriasis.

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Acne is a multifactorial inflammatory disease affecting pilosebaceous follicles. The initial event in the development of an acne lesion is abnormal desquamation of the keratinocytes that line the sebaceous follicle, which creates a microplug or microcomedone.

An increase in circulating androgens at the onset of puberty stimulates the production of sebum into the pilosebaceous unit. These events combine to create an environment within the pilosebaceous unit that is favorable for the colonization of the commensal bacteria, Propionibacterium acnes. (C. Acnes)

With proliferation, P acnes secretes various inflammatory molecules and chemotactic factors that initiate and perpetuate the local inflammatory response and possibly induce keratinocyte hyperproliferation as well.

Recent developments do not refute these elements, but rather refine particular aspects.

Interleukin-1a influences hypercornification of the infundibulum as well as the inflammatory response by inducing the production of vascular endothelial growth factor in dermal papilla cells and follicular keratinocytes of the pilosebaceous unit.

New retinoids have been developed based on controlling cellular proliferation and differentiation in the pilosebaceous unit by their action on nuclear receptors of cells.

Dermal inflammation is not due to presence of bacteria, but from biologically active mediators produced by Propionibacterium acnes.

The environment within the pilosebaceous unit is probably more important than the absolute number of P. acnes organisms. Indeed, the major role of the sebaceous gland appears to be supplying

Hyperkeritinization – or lack of appropriate desquamation

Increased sebum production

Excess P. Acnes – feeds off sebum

Immune and inflammatory response

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In my practice I have found these combinations to be effective. There is evidence to support combination therapy vs. monotherapy. These aren’t new concepts, but they are more reasonably priced and should theoretically be trialed first.

Differin – OTC

Salicylic acid in combination with clindamycin or benzoyl peroxide

OCP combined with topical retinol

Sodium sulfacetamide with benzoyl peroxide

Adapalene and benzoyl peroxide (Epiduo)

Minocycline for 1-3 months with topical adapalene (0.1% - 0.3%) started at the same time, but the topoical is continued for maintenance

Azelic Acid and Clindamycin

New EBP

Topical nicotinamide

Nicotinamide serves as the pyridine-3-carboxylic acid amide form of niacin, a component of the vitamin B complex. Topical nicotinamide 4% has been shown to be effective for mild to moderate acne (Nicotinamide 5% gel has been found to be as effective as clindamycin 2% gel for the treatment of mild to moderate acne vulgaris

The mechanisms of action are mainly due to its potent anti-inflammatory effect and inhibition of sebum production (Nicotinamide exerts its anti-inflammatory effects by inhibiting C. acnes, formerly P. acnes-induced chemokine IL-8 production in keratinocytes through interfering with NF-kappa B by inhibiting PARP-1 and mitogen-activated protein kinases (MAPK) pathways.

Only mild stinging or burning at the application site has been observed during topical treatment with nicotinamide . It is thought to be safe in pregnancy, although topical nicotinamide has not been formally assigned to a pregnancy category by the FDA. Nicotinamide is excreted in breast milk, but no data regarding topical nicotinamide use in women who are pregnant or lactating are available.

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J Am Acad Dermatol. 2017 Jun;76(6):1195-1197. doi: 10.1016/j.jaad.2017.01.013.

Generic, twice-daily minocycline versus branded, extended-release minocycline for acne: A retrospective comparison of treatment escalation.

Gupta P1, Shin T2, Sopkovich J3, Massick S3, Kaffenberger BH4.

What did this study show?

- Branded was more likely to be discontinued buy the patient (cost, side effects).

- There was additional administrative burden with prior authorization.

- Bottom line – no evidence to state that the branded gives any additional benefit.

New Company called Aspetic MD

https://www.asepticmd.com/

Chlorine Dioxide for Acne therapy

How does it work?

Direct, potent keratolytic

Anti-inflammatory – denatures extracellular inflammatory cytokines, rapidly oxidizes specific amino acids, does not oxidize other organic molecules, reacts rapidly with cysteine and disulfide bonds, inactivated by glutathione upon entrance to human cells

Also excellent for keratosis pilaris (especially on the faces of athletes in my experience)

Very mild, will not cause dryness or inflammation

J Am Acad Dermatol. 2017 Jun;76(6):1068-1076.e9. doi: 10.1016/j.jaad.2016.12.028. Epub 2017 Mar 11.

Isotretinoin treatment for acne and risk of depression: A systematic review and meta-analysis.

Huang YC1, Cheng YC2.

J Cutan Med Surg. 2018 Jan/Feb;22(1):58-64. doi: 10.1177/1203475417719052. Epub 2017 Jul 14.

Association of IsotretinoinWith Depression and Suicide: A Review of Current Literature.

Oliveira JM1, Sobreira G1,Velosa J2,3, Telles Correia D4,5, Filipe P4,5.

Prevalence of depression decreased by 40% after isotretinoin treatment

What can you tell the parents and patients prior to referral to dermatology?

- You are doubling the chance of depression and subsequent suicide if you DONT put them on isotretinoin. (Side note: If all other acceptable alternatives have been exhausted.)

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Novel combination for the treatment of acne differentiated according to gender: a new step towards personalized treatment.

G Ital Dermatol Venereol. 2018 Feb 7. doi: 10.23736/S0392-0488.18.05710-3.

Tolino E1, Skroza N2, Mambrin A2, Bernardini N2, Zuber S2, Balduzzi V2, Marchesiello A2, Proietti I2, Potenza C2.

Combination of a plant based topical treatment and oral supplementation

Plant agents (verbascoside, ocimum gratissimum) and keratolytic molecules (salicylic acid, gluconolactone, complex alpha-hydroxy acids).

Oral supplements contain biotin, probiotic, vitamin E, zinc, nicotinamide; in the formulation for males beta sitosterol and boswella serrata were added, the oral supplement for females contains myo-inositol and folic acid.

Results – satisfactory for mild to moderate acne

As always, if you have seasonal allergies, plant based therapies may not be for you, or may cause…

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Novan, Inc. is a clinical-stage biotechnology company focused on leveraging nitric oxide’s natural antiviral and immunomodulatory mechanisms of action to treat dermatological and oncovirus-mediated diseases.

Currently clinical trials for psoriasis, mollescum, atopic dermatitis, and hypertension.

Patients with severe acne have limited treatment options that are safe and accessible, and are in need of well-tolerated topical alternatives. This medication has been pretty impressive in this population.

Expected to be on the market in 2019

Atopic dermatitis (AD) is a disease characterized by relapsing eczema with pruritus as a primary lesion. Most patients have an atopic predisposition. Often requires long-term and routine administration of corticosteroids that frequently leads to significant adverse effects such as skin atrophy, telangiectasia, striae, hyper- and hypopigmentation, and tachyphylaxis.

The definitive diagnosis of AD requires the presence of all three features:

1) pruritus

2) typical morphology and distribution of the eczema

3) chronic and chronically relapsing course.

Acute Eczema Acute eczematous eruptions typically manifest grossly as juicy erythematous papules and

plaques and may display vesicles. Lesions may possess crust and scales as well. Histologically, this is characterized by spongiosis and a perivascular dermal lymphocytic infiltrate

Chronic Eczema Over time, eczematous lesions become progressively lichenified, transforming into

thickened plaques with accentuation of skin markings. There is matched by histological lichenification as well with epidermal acanthotic, hyperkeratotic and a continued dermal perivascular lymphocytic infiltrate.

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1) The use of topical corticosteroids and tacrolimus ointment as the main treatment for the inflammation.

2) Topical application of emollients to treat the cutaneous barrier dysfunction.

3) Avoidance of apparent exacerbating factors, psychological counseling and advice about daily life.

MOA: Unknown; inhibits T-cell activation by binding to intracellular protein FKBP-12 and complexes with calcineurin dependent proteins, inhibits release of inflammatory mediator

Tacrolimus (Protopic) – available in both 0.03 and 0.1% cream and Pimecrolimus 1% cream

Side effects: Stinging, burning, soreness, itching, headache, stomach upset, flu-like symptoms, increased sensitivity of the skin to hot/cold/pain/touch

Only the 0.03% formulation of Tacrolimus should be used in children 2 to 15 years old. Pimecrolimus 1% can be used in pediatric patients age two and up.

In the pipeline:

NCT02791308 – Double Blind Randomized trial -Study of Equivalence of Generic Pimecrolimus Cream 1% and Elidel® 1% in Subjects With Mild to Moderate Atopic Dermatitis

Cochrane Database Syst Rev. 2015 Jul 1;(7):CD009864. doi: 10.1002/14651858.CD009864.pub2.Topical tacrolimus for atopic dermatitis.Cury Martins J1, Martins C, Aoki V, Gois AF, Ishii HA, da Silva EM

In addition to the typical rigorous Cochrane review, the FDA adverse event log was also reviewed.

Tacrolimus 0.1% > than low-potency corticosteroids

Pimecrolimus 1%, and tacrolimus 0.03% = moderate-to-potent corticosteroids.

Tacrolimus 0.03% > mild corticosteroids and pimecrolimus

No cases of lymphoma

No evidence was found to support the possible increased risk of malignancies or skin atrophy with their use.

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Int J Nanomedicine. 2018; 13: 129–142. Published online 2017 Dec

22. doi: 10.2147/IJN.S150319 PMCID: PMC5743175 Tacrolimus nanoparticles based on

chitosan combined with nicotinamide: enhancing percutaneous delivery and treatment efficacy for atopic dermatitis and reducing dose

Kaiyue Yu,Yixuan Wang,Tao Wan,Yuanhao Zhai, Sisi Cao,Wenyi Ruan,Chuanbin Wu, and Yuehong Xu

Many reports have suggested that topical application of NIC had several beneficial effects, especially anti-inflammatory, antipruritic, and antimicrobial effects.

In this present study, the vehicle group containing NIC presented comparable efficacy in ameliorating AD-like clinical symptoms, decreasing epidermis thickening and inflammatory cell infiltration, and downregulating the serum total IgE.

The total dose was decreased to 1/3 of the normal dose of tacroliomus and therefore there were decreased side effects

FDA Approved 12/14/16

Crisaborole inhibits PDE4, resulting in increased levels of cyclic adenosine monophosphate (cAMP). Its exact mechanism of action for treatment of atopic dermatitis is unclear, but increased cAMP levels suppress production of proinflammatory cytokines. Like TCIs systemic absorption of crisaborole is minimal after topical administration.

cAMP-PDE activity in leukocytes is significantly elevated in patients with AD compared to healthy controls.

Preliminary studies show better clearance than TCIs

Stay tuned

Monoclonal antibody that inhibits interleukin-4 (IL-4) and IL-13 signaling by specifically binding to the IL-4R-alpha subunit shared by the IL-4 and IL-13 receptor complexes

Blocking the IL-4R-alpha subunit inhibits IL-4 and IL-13 cytokine-induced responses, including the release of proinflammatory cytokines, chemokines, and IgE

600 mg (ie, two 300-mg injections) SC once, and then 300 mg SC every other week

Can be used with or without topical corticosteroids

Topical calcineurin inhibitors may be used, but should be reserved for problem areas only (eg, face, neck, intertriginous, and genital areas)

Most patients will require additional topical treatment on dupilumab.

Not approved for pediatric patients…yet. Studies on patients 6 years to 18 years are ongoing.

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J Dermatol Sci. 2018 Feb 19. pii: S0923-1811(18)30094-X. doi: 10.1016/j.jdermsci.2018.01.016. [Epub ahead of print]

Dupilumab treatment in moderate-to-severe atopic dermatitis: A systematic review and meta-analysis.

Wang FP1,Tang XJ1,Wei CQ1, Xu LR1, Mao H1, Luo FM2.

Analysis provided evidence that dupilumab had an acceptable safety profile and resulted in clinically relevant improvements in signs and symptoms of AD.

Dose regimens of 300 mg qw and q2 w seemed to have similar benefits. Further long-term trials are required for confirmation.

J Am Acad Dermatol. 2018 Jan;78(1):62-69.e1. doi: 10.1016/j.jaad.2017.09.052. Epub 2017 Oct 4.

Risk of infection in patients with atopic dermatitis treated with dupilumab: A meta-analysis of randomized controlled trials.

Fleming P1, Drucker AM2.

Limited by the short follow-up time in most trials and the relatively low number of patients treated with dupilumab to date.

The study did indicate that Dupilumab is associated with a decreased incidence of skin infections and eczema herpeticum in adults with moderate-to-severe AD.

Trends seen in my text messages

- “What do I tell my patient to use when they react to EVERYTHING”

- Lots of pictures of hands

- ”My patient is allergic to their clothes”

- Essential oils – better because they are natural…right?

Soap – Cetaphil, CeraVe Baby, Mustela Baby, Neutrogena

Shampoo – T / Sal shampoo

Moisturizer – CeraVe

Deodorant – Certain Dry (only a couple nights per week with the application of hydrocortisone 2% cream in the am after). Native unscented www.nativecos.com

Toothpaste – Cleure (order online, Amazon had it for a while)

Gloves – Microtouch Nitra-free (Ansell) and Gammex Non latex sensitive (neoprene sterile gloves), Restore by Medline

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DDx:

Dorsal only -irritant contact dermatitis

Palmar only - endogenous

Vesicular – non psoriatic

Transgradiens cut off, thick scale –psoriasis

Fingertips – frictional (no pruritis) affects the pulps only

Patchy – staph based infection (nummular pattern)

Ask a lot of questions about what they do in their day. (ie hair dresser, chef, mechanic)

Cold water to rinse hands to avoid the breakdown of the lipid barrier

Rinse hands VERY WELL

Avoid Dish soap like the plague

Clobetasol 0.5% apply twice daily

For debilitating cases - Thioglycolic acid (nair, magic shave) improved penetration by 10x or more

Apply for 3 minutes, wipe and then apply clobetasol. Will be tender for a day or so, but…

Common cotton items in our every day life are releasing detectable formaldehyde: shirts (esp men’s work shirts, bedsheets, pillowcases, etc)

Truncal dermatitis as well as axillary

Use a detergent with low irritancy surfactants and put ½ cut of non fat powdered milk with the detergent – it is theorized that casein in the milk binds to the formaldehyde

This accumulates so you need to add it each time they do laundry

https://pubs.acs.org/cen/government/88/8836gov2.html

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Do not contain protein, so they claim that they are non-allergen inducing…unless you are allergic to the plant

Encourage spot testing if there is concern

Int J Dermatol. 2017 Jul;56(7):788-791. doi: 10.1111/ijd.13620. Epub 2017 Apr 23.

The use of topical minoxidil to accelerate nail growth: a pilot study.

Aiempanakit K1, Geater A2, Limtong P1, Nicoletti K3.

Accelerates nail growth

Meijer (60 grams) $22.99

Kirkland (6-60 ml bottles) $34.99

Rogaine brand - $53.99 at Wallgreens, $44.99 at Walmart

Get the men’s - I do not recommend the women’s formulation for anyone, especially for hair growth