Expert dermatologists provide an overview of vitiligo while reviewing presentation, diagnosis, and the goals of therapy related to current and future therapies.

DermView: Innovations in the Treatment of Vitiligo

Ashfaq A. Marghoob, MD, director of clinical dermatology and attending physician at Memorial Sloan Kettering Cancer Center in Hauppauge, New York, and colleagues explained in a presentation at the current Maui Derm for Dermatologists meeting in Maui, Hawaii, that while several challenges in diagnosing melanoma in Black patients may delay diagnoses and result in worse outcomes, efforts at early detection may result in excessive harm from the biopsy of normally occurring pigmented macules on the palms, soles and nail unit of Black patients.

 An early study from 1967 showed that 50% of Black patients have pigmented macules on volar surfaces, while Caucasian patients almost never have pigmented macules on palms and soles.

The presentation highlighted the differences in identifying melanoma in Caucasian and Asian skin vs Black skin; studies that identified dermoscopic criteria for melanoma were performed primarily in Caucasian and Asian patients. In particular, the parallel ridge pattern (PRP) is considered the hallmark of identifying early melanoma on the palms and soles in Caucasian and Asian skin, Marghoob said.

However, he went on to underscore that this criterion may not be reliable in differentiating melanoma from normally occurring pigmented macules often seen on the palms and soles of Black patients. He highlighted preliminary data showing that PRP can be seen within benign pigmented macules and even in the normal background skin of the palms and soles in Black skin. In addition to PRP not being a strong predictor of melanoma in Black skin, the presentation stated that benign pigmented macules in skin of color (SOC) are often greater than 7mm in diameter and may reveal a homogeneous brown color, both features suggestive of melanoma in Caucasian and Asian skin but not likely in Black skin. Marghoob stressed that using these diagnostic criteria, which have been validated for Caucasian and Asian skin, may result in harm and unnecessary biopsies in Black patients.

In a slide adapted from a 2021 publication by Marchetti et al and published in JAMA Dermatol, the incidence of melanoma reported between 1973-2011 in Caucasian, non-Hispanic populations was 27/100,000. The incidence in Black patients was 1/100,000. However, the 5-year survival rate was 20% lower in Black patients vs Caucasians: 73% compared to 93%, respectfully.

, Marghoob said that there may be multiple reasons accounting for the perceived delays in diagnosis of melanoma in Black patients.

Journal of the American Academy of Dermatology

 suggests that less access to medical care and preventive screenings as well as the misconception that darker races, particularly black patients, never develop skin cancer, leads to decreased awareness and a lack of public and physician education on the subject.

 reported that even after adjusting for age, sex, histology, stage, anatomic site, treatment, and socioeconomic status, there was still a significantly increased risk of death in Black patients relative to White patients indicating that there are many factors contributing to the delay in diagnosis.

Marghoob said that it is interesting to note that while the incidence of acro-lentiginous melanoma is less than 1/100,000 in both Black and white patients, it is the predominant subtype of melanoma seen in Black patients but the least common subtype in Caucasian patients. It is also interesting to note that acro-lentiginous melanoma has survival rates that are relatively similar: 83% in Caucasian patients vs 77% in Black patients.

“We need dedicated studies to determine the morphology of benign and malignant skin lesions in Black patients and use this data to determine the most robust criteria to help differentiate benign from malignant lesions in this population,” Marghoobtold

. “Health care equity does not mean providing the same care to all patients, but instead it means providing the most appropriate, personalized care to each individual with the aim of maximizing benefits and minimizing harms.”

Hawrluk E, High W, Marghoob A, Sullivan R. Pigmented lesion clinic part 1. Presented at: Maui Derm 2022; January 24 to 28, 2022; Wailea, Hawaii.

Lewis MG. Malignant melanoma in Uganda. (The relationship between pigmentation and malignant melanoma on the soles of the feet). 

. 1967;21(3):483-495. doi:10.1038/bjc.1967.56.

Marchetti MA, Adamson AS, Halpern AC. Melanoma and racial health disparities in black individuals-facts, fallacies, and fixes. 

. 2021;157(9):1031-1032. doi:10.1001/jamadermatol.2021.2215.

Gloster HM Jr, Neal K. Skin cancer in skin of color. 

. 2006;55(5):741-764. doi:10.1016/j.jaad.2005.08.063.

Zell JA, Cinar P, Mobasher M, Ziogas A, Meyskens FL, Anton-Culver H. Survival for patients with invasive cutaneous melanoma among ethnic groups: the effects of socioeconomic status and treatment. 

Wang Y, Zhao Y, Ma S. Racial differences in six major subtypes of melanoma: descriptive epidemiology. 

. 2016;16(1):691. Published 2016 Aug 30. doi:10.1186/s12885-016-2747-6

Articles

Melanoma in Black patients presents unique challenges for dermatologists due to clinical diagnostic differences, provider bias, and a lack of patient awareness, according to a presentation given at Maui Derm 2022.

Challenges in Diagnosing Melanoma in SOC

Ilya Petrou, MD, is a contributing writer for 

In his presentation, “New Drugs and Therapies in 2022” at the current Maui Derm for Dermatologists meeting in Maui, Hawaii, and virtual, Neal Bhatia, MD, highlighted new atopic dermatitis (AD) and psoriasis treatments to watch this year.

Bhatia is the director of clinical dermatology at Therapeutics Clinical Research, in San Diego, California.

According to Bhatia, PAD technology has shown advantages in topical dermatologic therapy, as seen in a novel betamethasone and calcipotriene combination treatment in the cream vehicle (Wynzora; MC2 Therapeutics).

PAD technology, according to the MC2 Therapeutics website, enables the mixing of oil and water into a cream using just a fraction of the emulsifier required in conventional creams and lotions.

In a recent study, researchers found that twice-weekly topically applied calcipotriene/betamethasone dipropionate cream as proactive management of plaque psoriasis was well-tolerated over the 52-week study period and demonstrated superior efficacy to reactive management in a 251-patient study cohort.

“Wynzora cream is the first launch by MC2 with the PAD technology allowing for stability of the combination of active ingredients for psoriasis and flexibility for use on the body and scalp,” Bhatia said. “The oil and water balance, as well as the elegance of the vehicle, promote significant compliance and efficacy outcomes.”

Patients with moderate to severe AD can benefit from the recently FDA approved ruxolitinib cream 1.5% (Opzelura; Incyte), the first topical janus kinase (JAK) inhibitor of JAK 1 and JAK 2, Bhatia said. This novel medication may offer patients with moderate to severe AD a good treatment option to frequently used treatments including topical corticosteroids and the calcineurin inhibitors tacrolimus and pimecrolimus, he added.

 In addition, the FDA most recently approved upadacitinib (Rinvoq; AbbVie)

 the first 2 oral JAK 1 inhibitor medications for the treatment of moderate to severe AD. According to Bhatia, this offers AD patients more treatment options beyond the more traditional therapies such as corticosteroids, which he said have long-term use issues.

“As opposed to the calcineurin inhibitors which work to block the neurotransmitter NF-AT with subsequent effects on inflammation, ruxolitinib as a [JAK] inhibitor works to stop the progression and processing of cytokines by preventing dimerization of receptors and phosphorylation of STAT proteins that carry messages to the nucleus for transcription,” Bhatia said. “In many ways, the difference is that topical calcineurin inhibitors can mop up the inflammation mess while JAK inhibitors will turn off the faucet to stop the inflammation progress.”

Roflumilast (ARQ-151, Arcutis Biotherapeutics, Inc) represents a novel phosphodiesterase type 4 (PDE4) topical therapy under investigation that have been found to be effective in AD, psoriasis, and seborrheic dermatitis. Tapinarof (DMVT-505, Dermavant Sciences, Inc) is a therapeutic aryl hydrocarbon receptor modulating agent (TAMA) that is a topical therapy in development for both plaque psoriaisis and AD. The once daily topical formulation of roflumilast cream, foam or lotion, is a highly potent and selective inhibitor of PDE4, Bhatia said, having a good efficacy in AD, psoriasis, seborrheic dermatitis, and vitiligo.

Tapinarof is an investigational topical aryl hydrocarbon receptor-modulating agent that has been found to decrease oxidative stress and inflammation in psoriasis and AD, as well as an increase in skin barrier normalization, Bhatia said. Recent phase 3 trials of tapinarof cream for plaque psoriasis found that tapinarof 1% cream applied once daily was superior to vehicle control in reducing plaque psoriasis over 12 weeks.

According to Bhatia, it is up to dermatologists to determine how they apply new drugs and their mechanisms of action, as well as the new vehicles where intolerance or sensitivity are potential obstacles.

“The new molecules tapinarof and roflumilast will be exciting topical additions for dermatologists to reduce dependence on steroids as well as treat safely for the long run without risks of atrophy or tolerance. The newly approved oral JAK Inhibitors for [AD] are also going to change the game for us, adding a new strong option along with steroids and biologics,” Bhatia said.

Bhatia is an advisor and consultant investigator for with AbbVie, Almirall, Arcutis Biotherapeutics, Arena, Biofrontera, Bristol Myers Squibb, Boehringer Ingelheim, Dermavant Sciences, EPI Health, Ferndale, Foamix, Galderma, Incyte, ISDIN, Johnson & Johnson, LaRoche-Posay, LEO Pharma, Eli Lilly and Company, Ortho Dermatologics, Pfizer Inc, P&G, Regeneron Pharmaceuticals, Sanofi Pharmaceuticals, Stemline, Sun Pharma, and Vyne Therapeutics, and an investigator for Arcutis Biotherapeutics, Biofrontera, Bristol Myers Squibb, Boehringer Ingelheim, Dermavant Sciences, Galderma, LEO Pharma, Eli Lilly and Company, and Ortho Dermatologics.

Rosen T, Bhatia N. New drugs and therapies in 2022. Presented at: 2022 Maui Derm for Dermatologists; January 24 to 28, 2022; Maui, Hawaii.

PAD cream technology. PAD Technology. Accessed January 21, 2022. https://padcream.com

Lebwohl M, Kircik L, Lacour JP, et al. Twice-weekly topical calcipotriene/betamethasone dipropionate foam as proactive management of plaque psoriasis increases time in remission and is well tolerated over 52 weeks (PSO-LONG trial). 

.2021 May;84(5):1269-1277. doi: 10.1016/j.jaad.2020.09.037. Epub 2020 Sep 18. Accessed January 20, 2022.

Rivqoq (unadacitinib) receives U.S. FDA approval for active psoriatic arthritis. AbbVie. Press release. Published December 14, 2021. Accessed January 20, 2022. 

https://news.abbvie.com/news/press-releases/rinvoq-upadacitinib-receives-us-fda-approval-for-active-psoriatic-arthritis.htm

U.S. FDA Approves Pfizer’s Cibinqo (abrocitinib) for adults with moderate-to-severe atopic dermatitis. Pfizer. Press release. Published January 14, 2022. Accessed January 20, 2022. 

https://www.pfizer.com/news/press-release/press-release-detail/us-fda-approves-pfizers-cibinqor-abrocitinib-adults

Lebwohl MG, Stein Gold L, Strober B, et al. Phase 3 Trials of Tapinarof Cream for Plaque Psoriasis. 

. 2021 Dec 9;385(24):2219-2229. doi: 10.1056/NEJMoa2103629. Accessed January 20, 2022.

Neal Bhatia, MD, highlights the most exciting new drugs and therapies in atopic dermatitis and psoriasis in his presentation at the current Maui Derm for Dermatologists meeting.

New Molecules, PAD Tech Expand Treatments for Psoriasis and AD

Continued research has led to several exciting therapeutic developments in drug delivery technologies as well as new and experimental medications for a wide spectrum of dermatological diseases and conditions including acne, rosacea, and pruritus. 

In his presentation at the 2022 Maui Derm for Dermatologists meeting, Neal Bhatia, MD, director of clinical dermatology, at Therapeutics Clinical Research in San Diego, California, urged dermatologists not to be afraid of innovation. Instead, he called on them to be aggressive in learning about new treatments and putting these novel therapies and treatment modalities into daily practice, some of which may become first-line therapies.

Acne and Rosacea Benefit from Drug Delivery Advances

New drug delivery technologies have given rise to the development of novel formulations of medications that have shown to be helpful in an increasing number of dermatological diseases and conditions including acne, rosacea, and psoriasis.

FDA-approved in mid-2021, encapsulated products such as 5% encapsulated benzoyl peroxide (E-BPO) cream (Epsolay; Sol-Gel Technologies Ltd) and Twyneo (Sol-Gel Technologies Ltd), a combination of microencapsulated tretinoin 0.1% and microencapsulated BPO 3% cream, provided treatment options with enhanced tolerability thanks to their controlled release of encapsulated material, according to Bhatia. He added that this also resulted in more effective treatment outcomes.

In December of 2021, Teva Pharmaceuticals, a US affiliate of Teva Pharmaceutical Industries Ltd, announced the launch of an authorized generic of Epiduo Forte gel 0.3%/2.5%, another benzol peroxide-based treatment.

“Twyneo for acne is probably going to replace some of the Epiduo Forte [adapalene and benzoyl peroxide, Galderma] presence since it is going generic. [Additionally,] adapalene [will be] available for rosacea soon as well. Twyneo may become a first-line treatment for acne given the demonstrated efficacy in the trials,” Bhatia said.

Molecule Stabilizing Technology (MST; Journey Pharmaceuticals) used in micronized minocycline in suspension mode has also been shown to improve treatment outcomes in patients with acne and rosacea by helping to optimize stability and efficient delivery of the active ingredient, he noted.

“Particle size reduction offers several advantages [in treating acne and rosacea) including improvement in contact between the active ingredient and the skin, increases in the number of particles to evenly cover the skin, penetration promotion through the stratum corneum, and enabling a smooth application,” Bhatia said.

Initially launched by VYNE Therapeutics, Amzeeq 4% is a topical formulation of minocycline FDA approved for the treatment of inflammatory lesions of non-nodular moderate to severe acne vulgaris in adults and children 9 years and older. Zilxi 1.5% is a topical minocycline for inflammatory lesions due to rosacea in adults. As of January 13, 2022, Journey Pharmaceuticals acquired the 2 products, along the MST technology.

The unique physical foam characteristics in the composition, Bhatia said, include myristyl and stearyl alcohols, coconut oil and soybean oil, and low surfactants.

“Both of these medications have shown good efficacy and reduce the exposure to oral dose which involve higher concentrations in the plasma and more adverse events including an increased potential for antibiotic resistance,” Bhatia said.

Shown to work for itch independent of histamine, strontium is an ingredient that has been found to help mitigate itch in patients with moderate to severe pruritus, regardless of pathogenesis. It is thought to interfere with receptors and/or channels that rely on calcium. According to Bhatia, strontium works almost instantaneously upon application for up to 5 hours and can be useful for localized itching such as prurigo nodules or other cases with very focused itching.

“For many who have tried the new Dermeleve cream [Advanced Derm Solutions LLC], made with strontium, ceramides, and other ingredients that directly counter the impact of itch from C-nerve fibers and other contributing factors, the patient experience has been significantly positive as they describe the impact on quality of life. It is an OTC [over-the-counter] product and works really well for localized pruritus,” Bhatia said.

Other medications that have shown efficacy in improving itch include nalbuphine, an opioid receptor antagonist, and difelikefalin, an opioid receptor agonist that works well in patients with moderate to severe itching commonly seen in patients with kidney disease and other pruritic dermatoses, he added.

Sol-Gel Technologies announces FDA approval of TWYNEO. Galderma. Press release. Published July 27, 2021. Accessed January 21, 2022. 

https://www.galderma.com/us/news/sol-gel-technologies-announces-fda-approval-twyneor

Teva announces launch of an authorized generic of Epiduo forte gel (adapalene and benzoyl peroxide gel 0.3%/2.5%), in the U.S. Teva Pharmaceuticals. Press release. Published December 1, 2021. Accessed January 21, 2022. 

https://www.tevapharm.com/news-and-media/latest-news/teva-announces-launch-of-an-authorized-generic-of-epiduo-forte-gel-adapalene-and-benzoyl-peroxide-gel-0/

Journey Medical Corporation acquires two FDA-approved topical minocycline products and molecule stabilizing technology (MST) franchise from VYNE Therapeutics, Inc. Journey Medical Corporation. Press release. Published January 13, 2022. Accessed January 21, 2022. 

https://www.globenewswire.com/news-release/2022/01/13/2366289/0/en/Journey-Medical-Corporation-Acquires-Two-FDA-Approved-Topical-Minocycline-Products-and-Molecule-Stabilizing-Technology-MST-Franchise-from-VYNE-Therapeutics-Inc.html

Patients suffering from several dermatologic diseases and conditions including acne, rosacea, and pruritus can largely benefit from the new and exciting therapies and treatment modalities that have recently become available.

New Drugs and Therapies in 2022: Acne, Rosacea, and Pruritus

Helen M. Torok, M.D., is medical director for the Dermatology & Surgery Center at Trillium Creek. A noted expert in medical and cosmetic dermatology, she also is a Dermatology Times Editorial Advisor.

Transcript:
Christopher G. Bunick, MD, PhD:

 Let’s go on to our second patient case. The second patient is a 60-year-old man or woman with plaque psoriasis covering 45% body surface area along with hand and knee arthralgias. This patient has been on an anti–TNF [tumor necrosis factor]–alpha agent for approximately 18 months. After initial clearance of the skin and resolution of joint pains, both are starting to flare again. Dr Lebwohl, the first question goes to you. How and when do you decide a change of therapy is warranted?

 I usually change therapies at around 3 months if I don’t see a benefit at all. For the IL-17s, I start to get nervous if I don’t see a benefit at 4 weeks, but I’ll often continue the patient to 3 months. The same is true for the TNF blockers and the IL-23 blockers.

 Dr Wu, what do you think contributed to the initial treatment failure of this patient case?

 It sounds as if this patient maybe had some good clearance before but developed some antidrug antibodies against the TNF inhibitor, in which case, it’s not working well anymore. That would be my guess.

 Why might it not work anymore? Is there any science behind why it may stop working?

 I’m wondering if he took a long break in between. It seems to me that the antidrug antibodies tend to occur if they’ve taken a long break between doses. Maybe he lost some drug coverage for a few months, or maybe he took a drug holiday on his own and then came back to it and it stopped working. In my experience, that’s usually the most likely reason why antidrug antibodies tend to occur, not so much because they’re on it for 5 years straight. It could still occur in that scenario, but it’s more from taking a break.

 Dr Torok, what are some barriers to switching from a biologic? We’ve talked about switching. It’s OK to switch within a class because the molecular epitope of these drugs is even different within a class. It’s also OK to switch between a class. What barriers have you seen in your clinic to implementing a switch?

 The main barrier is insurance coverage. A lot of these insurance carriers have contracts with different pharmaceutical companies, and they may not have a contract with the drug that I want to switch to. Or it may be prohibitively more expensive for the patient. That’s what I find. I don’t have trouble switching agents, but I have trouble with the reimbursement.

 Would anyone else like to add to that regarding the barriers you’ve experienced in clinic?

 I’ll emphasize what Helen said. It’s the insurance company barriers. The AAD [American Academy of Dermatology] and the National Psoriasis Foundation have pursued step-therapy legislation, which exists in 28 states. The problem with the step-therapy legislation is that the insurer can still deny your prescription, and if you don’t appeal it, they’ve won and your patient has lost. But if you appeal it in step-therapy states, it’s usually pretty easy to get that denial overturned.

 You mentioned appeal. That’s an important thing. Do any of you use the AAD prior authorization appeal tool?

 I wrote the tool. I wrote all the letters for psoriasis and many of the others as well. The reason I did that was because I was coming to my office. At times I had a pile of charts taller than I am, and I had to dictate appeal letters. I’m not that tall, but it was quite frustrating. I got good at it. It would take me about 2½ minutes per appeal, then I’d hand that pile of paper charts back to my secretary, and she’d type out the letters and send them out. We put together a template for almost every drug in every disorder that exists in dermatology. They’ve been highly effective. They’ve been used by thousands of our colleagues, and I never get that pile of charts in my office anymore. I give the denial to someone in my office, they go to aad.org/priorauth, and it takes them 30 seconds to generate a denial appeal. It works most of the time.

 I’ve used that tool. I thank you for contributing to that tool, and I encourage all our viewers who haven’t used it to go to the American Academy of Dermatology website and look up this prior authorization tool. It makes your life easy, but more important, it will help your patients when they get their biologic.

Videos

Moving on to the second patient case, panelists discuss switching therapy at treatment failure for plaque psoriasis.

Plaque Psoriasis Patient Case 2: Switching Therapy at Treatment Failure

 and joined the MJH Life Sciences team in September 2019. She graduated from Cleveland State University in 2018 with a bachelor's degree in journalism and promotional communications. She enjoys yoga, hand embroidery, and trying new restaurants. You can reach her at 

This week, January 24 to 28, the Maui Derm for Dermatologists conference will be held in Maui, Hawaii, and virtually, with an agenda packed full of presentations including, “in-depth, cutting-edge material covering a wide array of medical, cosmetic, coding/billing and CLIA certification topics in dermatology,” according to the Maui Derm website.

According to the site, as a result of attending the meeting, attendees should be able to:

Explain the pathogenesis of various dermatological conditions

Cite the mechanisms of action of drugs and therapies that are commonly prescribed by the dermatologist

Describe potential adverse effects and resistance issues that may be related to the use of drugs and therapies prescribed by clinicians in dermatology

Define appropriate outcome measures for the optimal follow-up of patients with dermatologic diseases as well as those receiving surgical and cosmetic procedures

Assess the data related to emerging therapies for the treatment of a variety of dermatologic diseases

Recognize the important role of clinician/patient communication

 This annual presentation, dubbed the “Neal and Ted show” discusses new drugs and therapies in dermatology and how they will be used in 2022.

Physicians discuss actinic keratosis and Non-Melanoma Skin Cancers (NMSC), along with challenging clinical cases and sceneries will be discussed.

Leading authorities will discuss a wide range of topics in pediatric dermatology.

Experts discuss the latest approaches to treating vitiligo, melasma, and other disorders of pigmentation.

Make sure to keep up to date with the latest in coverage from the event and subscribe to 

Maui Derm begins today in Maui, Hawaii, offering a multitude of presentations and workshops for the dermatology community.

Live from Maui Derm for Dermatologists

 Matt, do you have any words of wisdom for our colleagues who are trying to tackle this for the first time? We have a great drug, but there’s that little wrinkle because of the box warning. Would you encourage people to give it a try? If they’re worried, should they try to start on areas like the face where you know it’s going to be localized?

Everything is a trade-off. It’s not like the question we’re asking is no treatment vs the topical steroid. The question we’re asking is: which is better, topical steroid vs this, or other non topical non steroidals vs this is. We know that in terms of speed and efficacy, there isn’t another nonsteroidal that has an effect like this.

When you prescribe this for the first time or 2, ask your patient to call and leave a message after they’ve used it for a couple of days because the feedback I’ve gotten from patients has been that they’ve never experienced anything like the itch relief before, and this works quickly. To me, that’s what makes this drug worth having that conversation about the black-box warning. What makes it worth having a conversation about the box warning is that this is the fastest, most effective topical-free atopic dermatitis treatment that I’ve ever seen in my clinical practice.

I’m purposely not making that a comparative statement with any other drug because we don’t have a head-to-head trial that was adequately powered to determine anything like that. But having treated atopic dermatitis and contact dermatitis for the last 20 years, that’s all that I see. I’ve never seen a drug like this, and that makes it worth having the short conversation about the box warning.

 I agree. We see rapid onset of efficacy, rapid onset of its reduction, and really good tolerability, and we don’t see the stinging and burning that we might expect to see from a nonsteroidal option. It’s a drug that can be used on multiple body surface areas. It’s for short term, which to me means twice a day for up to 8 weeks, but you can stop earlier if the skin is controlled before that. For noncontinuous long-term means, they go on and off, as needed, as that disease comes back.

Thank you, Matt, for this wonderful discussion. This is a complicated issue, and you’ve helped simplify things quite a bit. I’d like to thank our viewing audience as well. We hope you found 

 to be rich and informative. Thanks so much.

Linda Stein Gold, MD, and Matthew Zirwas, MD, share some advice for clinicians on how to discuss JAK inhibitors with patients.

Advice for Clinicians on JAK Inhibitors

Evolving research on the pathogenesis and underlying causes of psoriasisis doing more than fueling a robust pipeline; it is changing the way dermatologist assess individual patient needs and optimally manage their skin disease and quality of life (QOL). Linda Stein Gold, MD, detailed how best to use theseadvances to develop more effective, patient-centric treatment plans in her presentation at Maui Derm for Dermatologists 2022 held in Maui, Hawaii.

Previously, she noted, topical corticosteroids and nonsteroidal agents such as vitamin D used either as a monotherapy or combination therapy were main stays. They often served as first-line treatment and informed the scope of treatment modalities.

However, this generation of topical and oral treatments opens up more adaptable approaches, particularly for patients with mild to moderate psoriasis, said Stein Gold, who is director of clinical research and division head of the Department of Dermatology at Henry Ford Hospital in Detroit, Michigan. “A lot of patients [with mild to moderate disease] have given up on getting their psoriasis under control, and they need to demand more. We need treatment options that will allow for better efficacy and long-term disease control.”

“Contrary to popular belief, localized psoriasis is not easier to clear than more diffuse disease,”Stein Gold said. “In fact, localized psoriasis can be equally if not more challenging to treat [than diffuse disease] and very difficult to get under control. It is also important to keep in mind that even mild disease can have a profound impact on the patient’s quality of life.”

Research data supports that conclusion. She cited a 2016 study

 comparing disease-associated cytokine expression in the skin between mild and severe psoriasis. Paradoxically, researchers found that mild psoriasis was characterized by higher numbers of T cells in skin lesions, higher interleukin (IL)-17A expression, and stronger expression of the core psoriasis transcriptome.

Results of 2021 study for which Stein Gold was lead author explored a new solution for combatting mild to moderate psoriasis.

 She and fellow researchers investigated the efficacy and safety of apremilast (Otezla; Amgen Inc) in a large cohort of patients with mild to moderate plaque psoriasis and found treatment to be effective with a safety consistent with the established safety profile of the medication.

According to Stein Gold, this novel oral phosphodiesterase 4 (PDE4) inhibitor may be a good option forpatients with mild to moderate localized psoriasis. In her view, it couldbe particularly useful for long-term management.

New medications and formulations may also address unmet needs for areas that could be difficult to treat with traditional topical creams alone, especially scalp and nail psoriasis. Also in clinical trials are studies exploring combination therapies for apremilast and foam formulations that target plaque psoriasis.

Durability has been an ongoing therapeutic issue, Stein Gold said. Potent topical corticosteroids are a short-term solution to a long-term disease like psoriasis and as such, nonsteroidal treatment options would be more desirable, particularly for long-term treatment and management plans, she added.

Many clinicians report that nonsteroidal options do not work well in psoriasis cases, according to Stein Gold. In her experience, dermatologists have not had the nonsteroidal options that provided patients with sufficient levels of efficacy and tolerability—until now.

“The new nonsteroidal options such as tapinarof (Dermavant Sciences, Inc) and roflumilast (ARQ-151; Arcutis Biotherapeutics, Inc) give us efficacy and tolerability that we have not seen in the past,” she said. “The foam vehicle of roflumilast is a wonderful option for scalp psoriasis. Tapinarof gives some patients a durable remission that may allow them a drug holiday that lasts on average 4 months. Fortunately, the safety profile is also favorable, with the most common side effect being mild to moderate folliculitis occurring in about 20% of patients,” added Stein Gold.

Another misconception is that nonsteroidal options cause local skin irritation and tend to sting and burn. A well-tolerated topical medication is critical to enhancing patient adherence and, thereby, ultimately achieving the desired efficacy. The new topical PDE4 inhibitor roflumilast and the first-in-class nonsteroidal small molecule tapinarof (aryl hydrocarbon receptor agonist) could positively impact the treatment regimens of psoriasis patients particularly because of their excellent tolerability, Stein Gold said.

“The fact that we have good tolerability with both new options allows ease of use for sensitive areas including the face, skin folds and genital area,” she added.

These new nonsteroidal medications have not been studied yet in combination therapy. However, if they are FDA approved, Stein Gold said that they will very likely be used in combination with topical corticosteroids.

“We are very fortunate to have some great options in the pipeline that will help us to help our patients. I hope that we continue to see new molecules for topical therapy as this represents the majority of the medications that we prescribe,” Stein Gold said. “Developing new drugs is an expensive endeavor, as less than 10% of drugs that enter phase 1 ever get FDA approved.”

Stein Gold is an investigator, advisor and/or speaker for AbbVie, Amgen Inc, Arcutis Biotherapeutics Inc, LEO Pharma, Ortho Biologics, Dermavant Sciences, Pfizer, Eli Lilly and Company, Novartis, UCB, and Bristol Myers Squibb.

1. Stein Gold L, Strober B, Leonardi C, et al. Psoriasis update: 2022. Presented at Maui Derm for Dermatologists 2022. Held January 24-28, 2022, in Maui Hawaii and virtual.

2. Kim J, Bissonnette R, Lee J, Correa da Rosa J, et al. The spectrum of mild to severe psoriasis vulgaris is defined by a common activation of il-17 pathway genes,but with key differences in immune regulatory genes.

 (2016) 136, 2173e2182; doi: 10.1016/j.jid.2016.04.032 Accessed January 21, 2022.

3. SteinGold L, Papp K, Pariser D, et al. Efficacy and safety of apremilast in patients with mild-to-moderate plaque psoriasis: Results of a phase 3, multicenter, randomized, double-blind, placebo-controlled trial. 

2022 Jan;86(1):77-85. doi:10.1016/j.jaad.2021.07.040. Epub 2021 July 31. Accessed January 21, 2022.

New and exciting topical and oral therapies for psoriasis have changed the way dermatologists treat and manage their psoriasis patients.

Solve the Challenges of Mild to Moderate Psoriasis 

The latest additions to the armamentarium for actinic keratosis (AK) and nonmelanoma skin cancers (NMSC) combine efficacy with a reduction in adverse effects (AEs) from irritation to cosmetic concerns, according to George Martin, MD, program chairman of Maui Derm for Dermatologists 2022and a dermatologist at Dr George Martin Dermatology Associates in Kihei, Hawaii. He delved into new therapeutic and management options for cutaneous oncology in a presentation at Maui Derm for Dermatologists 2022 held in Maui, Hawaii.

The ever-increasing number of treatment options for AKs can be challenging to navigate. Recognizing that, the American Academy of Dermatology (AAD) recently published its recommendations for the treatment and management of AKs to help clinicians choose optimal treatment plans for their patients.

Although helpful, Martin pointed out some omissions.

“There were no real surprises with the AAD’s guidelines for the treatment of AKs. Imiquimod and 5-FU have withstood the test of time and they are very good therapeutic agents. However, the guidelines did not address basic compliance, which is abysmal for local therapies,” Martin said.

He also cited a need for guidance in other important including actinic cheilitis, a significant problem in this patient population, a novel combination therapy with 5-fluorouracil (5-FU) and calcipotriene, 1% tirbanibulin (Klisyri, Almirall), as well as how to best manage immunocompromised patients in respect to field therapy to manage their actinic damage.

The combination of 5-FU cream with the synthetic vitamin D analogue calcipotriene used in equal parts twice daily for 4 days can achieve a very good clearance of lesions, according to Martin. Last year’s FDA approval of 1% tirbanibulin applied daily for 5 days for the treatment of AKs is another milestone he would like to see the guidelines address.

“Treatment for 5 days with the 1 percent tirbanibulin is a game changer for our AK patients, effectively clearing lesions with minimal cosmetic concerns, allowing them to further participate in daily social activities,” Martin said. “We are getting good efficacy with the medication on the face but less so on the scalp. What we are not seeing is a tremendous amount of irritation, which increases tolerability and patient adherence to the therapy.”

He added that milder irritation also means patients are more willing to repeat therapy as needed because they are not experiencing significant downtime with ulcerations and erosions seen with other standards of treatment.

However, he recommended reminding patients that the treatment is designed to treat a 25-cm

 skin surface, and that there is no data available yet on how to treat larger surface areas such as those involved in field cancerization.

The cost for tirbanibulin presents an issue and as such, Medicare patients have little access to the medication. Martin often uses tirbanibulin as a first-line treatment for AKs but for those patients who cannot afford the medication, he will treat with the 5-FU as monotherapy for 1 to 2 weeks and repeat in a month. For more resistant field cancerization, he prescribes a 5-FU and calcipotriene combination twice a day for 4 days. This combination therapy affords a more aggressive short-term treatment option when compared to a week 1 or 2 of other therapies in Martin’s experience.

Developments in Photodynamic Therapy (PDT)

One of the most impactful recent changes in the entire field of AKs and field cancerization is the development of an improved PDT treatment protocol. A 2020 study found that applying topical 20% aminolevulinic acid (ALA) solution to patients’ face and/or scalp immediately before 30, 45, or 60 minutes of blue light treatment (rather than applying the ALA topical with a 1-hour preincubation before PDT), showed “nearly identical lesion clearance” with the conventional regimen at 3 months (as determined by statistical testing of noninferiority plus or minus 15% margin) with “significantly less paid during simultaneous illumination”, wrote the authors.

“This optimization of PDT changed our world and the way we treat our AK patients,” Martin said. “It defined the parameters to make it painless and highly efficacious. The data proved that this regimen is equal to the standard 1-hour incubation and 1000 seconds of blue light. That’s a milestone since patients can get treated in a half hour and go home and have an effective therapy. Most importantly, PDT is covered by Medicare so Medicare patients can now have a field therapy that is both effective and painless.”

Disseminated superficial actinic porokeratosis (DSAP) is an inherited keratinization disorder characterized by small, discrete, and slightly pruritic pink-to-brown circular macules with slightly raised borders on the arms and legs. The skin condition is associated with gene mutations of the mevalonate pathway involved in cholesterol synthesis. According to Martin, the more effective treatments currently available often scar the skin. In his view, other modalities have proven ineffective for clearing these that also have an increased association with cutaneous squamous cell carcinoma (cSCC).

Possible causes of DSAP include the skin’s lack of cholesterol because of the cholesterol metabolism defect or a build-up of a toxic intermediates that is triggering the disease process. Recent studiesevaluating the treatment of DSAP with a topical application of a cream containing both cholesterol to supplement the skin, and a statin to block the synthesis pathway, could achieved very dramatic clearance outcomes in small cohorts of patients.

“This novel approach to treat DSAP blocks at the very beginning of the cholesterol pathway so you do not get the build-up of the toxic intermediates,” Martin said.

According to Martin, one of the most important developments of late in the treatment of NMSC is the advent of the PD1 inhibitor cemiplimab (Libtayo; Regeneron Pharmaceuticals, Inc, and Sanofi-Aventis). This relatively new treatment option is FDA approved for cSCC in patients who have locally advanced (laCSCC) or metastatic (mCSCC) cutaneous squamous cell carcinoma. These are patients who have usually failed excision and/or radiation therapy. Most recently, it is also approved for use in patients with advanced basal cell carcinoma (BCC) who previously were treated with a hedgehog pathway inhibitor (HHI) or for whom a HHI is not appropriate.

“Cemiplimab offers our NMSC patients an effective systemic treatment option to help them control or regress their lesions, and offers a lot of hope, particularly where other therapies failed. The medication can help increase the longevity and quality of life, which is really huge for these patients suffering from this very challenging to treat chronic disease,” Martin said.

Martin G, Rosen T, Stockfleth E, Schmults C. Cutaneous Oncology. Presented at: Maui Derm for Dermatologists 2022. Held January 24 to 28, 2022, in Maui, Hawaii and virtual.

Eisen DB, Asgari MM, Bennett DD, et al. Guidelines of care for the management of actinic keratosis. 

Kaw U, Ilyas M, Bullock T, Rittwage L, Riha M, et al. A regimen to minimize pain during blue light photodynamic therapy of actinic keratoses: Bilaterally controlled, randomized trial of simultaneous versus conventional illumination. 

.2020 Apr;82(4):862-868. doi: 10.1016/j.jaad.2019.09.010. Epub 2019 Sep 13.

Byth LA, Byth J. Topical simvastatin-cholesterol for disseminated superficial actinic porokeratosis: An open-label, split-body clinical trial. 

.2021 Aug;62(3):310-313. doi: 10.1111/ajd.13601.Epub 2021 May 24.

Atzmony L, Lim YH, Hamilton C, Leventhal JS, Wagner A, Paller AS, Choate KA. Topical cholesterol/lovastatin for the treatment of porokeratosis: A pathogenesis-directed therapy. 

.2020 Jan;82(1):123-131. doi: 10.1016/j.jaad.2019.08.043.Epub 2019 Aug 23.

Mono- and combination therapies offer choices for treatments that clear skin with fewer adverse effects.

AK, SCC Treatments Focus on Efficacy, Tolerability, Durability

Dermatologists need a variety of treatments used in conjunction to effectively treat hyperpigmentation disorders in patients, according to Pearl E Grimes, MD, director of the Vitiligo and Pigmentation Institute of Southern California and clinical professor in the division of dermatology at the David Geffen School of Medicine at the University of California Los Angeles.

She gave a comprehensive assessment of treatments for providers at the current Maui Derm for Dermatologists 2022 meeting in Maui, Hawaii.

 Grimes explained that hyperpigmentation can cause patients great distress, so dermatologists need a strong working knowledge about treatment – not just types, but how to use them in a multimodal manner for effective combination.

Grimes said that the first line of treatment is photoprotection in the form of sunscreen, with tinted products that block visible light (such as those containing iron oxide) in addition to ultraviolet light. Next, she said oral antioxidants such as polypodium leucotomose, lyposomal glutathione, and pycnogenol/grape seed extract have been proven effective in treating patients with hyperpigmentation. In addition to being used orally, Grimes reported that vitamin E and niacinamide can be used topically. Finally, she said silymarin is an effective topical antioxidant.

The next tools in the box that Grimes listed were topical lighteners. These include a wide variety of treatments: retinoids, glucosamine, niacinamide, protease inhibitors, soybean milk extract, topical steroids, salicylic acid, lactic acid, and glycolic acid, among others.

 This category also includes hydroquinone formulations, which are supported by multiple global studies, and new paradigms that include many non-hydroquinone agents: among them cysteamine, tranexamic acid (which can also be used orally– but Grimes said that this should not be used on women taking birth control pills or patients with vascular orautoimmune issues due to rare thromboembolic phenomena), and malassezin whose effectiveness Grimes featured during her presentation. In particular, she noted how a lower dose (250 mg) of transexamic acid was actually more effective for patients than a higher dose of 500 mg in a 28-week study by Chowdhary et al.

 She pointed out that oral transexamic acid is also used with other topicals.

Grimes and colleagues have conducted the world’s first novel proof of concept study of malassezin that assesses its lightening effects and safety in facial hyperpigmentation treatment. The results show strong lightening effects from baseline to four weeks. This study’s clinical data has been accepted for publication by the 

, and the histology has been accepted by the 

The next set of tools are resurfacing procedures

Grimes said. She explained that these include chemical peels, microdermabrasion, microneedling, platelet-rich plasma therapy, ablative and non-ablative lasers, and intense pulsed light. Grimes noted that lasers can be difficult based on skin type: she said the darker the skin, the greater the risk.

, Grimes said that treating hyperpigmentation “is not a one trick pony – it requires a stable, all moving synchronously, dancing and bobbing to achieve a win.” She stressed the multimodal approach to successfully treat patients and help ease their distress over hyperpigmentation. “Whether it is melasma or post-inflammatory hyperpigmentation, or even vitiligo, pigmentation disorders are psychologically devastating for patients and have a profound impact on one’s quality of life,” she said.

1. Grimes PE. Disorders of hyperpigmentation: what’s new?. Presented at: Maui Derm 2022; January 24 to 28, 2022; Wailea, Hawaii and virtual.

2. Chowdhary B, Mahajan VK, Mehta KS, et al. Therapeutic efficacy and safety of oral tranexamic acid 250 mg once a day versus 500 mg twice a day: a

Hyperpigmentation requires dermatologists to take a multimodal approach and be familiar with a menu of treatments, according to a presentation given at Maui Derm for Dermatologists 2022, held January 24 to 28, 2022 in Maui Hawaii, and virtual.

Hyperpigmentation Treatment Toolbox

Patients with moderate to severe atopic dermatitis (AD) have seen the pipeline continue to expand and that trend remains strong. Continued research has led to the development of new treatment options for patients with the skin disease such as the monoclonal antibody dupilumab (Dupixent, Sanofi/Regeneron Pharmaceuticals, Inc), which has been shown to have significantly improved outcomes in patients.

The dawn of novel JAK inhibitors such as upadacitinib (Rinvoq; Abbvie) for severe AD may possibly be even more effective than dupilumab, giving this patient population yet another safe and effective treatment option to help them clear their moderate to severe disease.

, researchers evaluated the efficacy and safety of upadacitinib versus dupilumab in a large cohort of adult patients with moderate to severe AD and found the oral JAK 1 inhibitor to be more effective than dupilumab. Data showed that upadacitinib worked more quickly upfront but both agents converged at about 60-70% EASI 75 (Eczema Area and Severity Index) by the end of the study at week 16. However, upadacitinib showed higher EASI 90 and EASI 100 with a greater reduction in pruritus. Data showed only minor differences in the safety profile regarding serious adverse events however larger studies are needed to confirm these findings.

Patients looking for maintenance options may also soon have a new possibility. Another novel treatment for AD under investigation is an autologous “microbiota replacement therapy.” An association between 

) and AD has long been recognized, and patients with AD are deficient in coagulase-negative 

 that has the capacity to produce antimicrobial peptides.

“Therapeutic bacteria have been used for gastrointestinal conditions (i.e., probiotics) and topical microbiota therapy is beginning to show hints of success,” said Hensin Tsao, MD, PhD, professor of dermatology and director, MGH Melanoma and Pigmented Lesion Center at Massachusetts General Hospital and professor of Dermatology at Harvard Medical School, both in Boston, who recently spoke at the Maui Derm for Dermatologists 2022 meeting.

, researchers studied the use of autologous bacteriotherapy to treat

 in patients with atopic dermatitis. Data showed a significant reduction of 

 count on treated skin compared to vehicle, clinically seen in the improvements of atopic dermatitis symptoms.

Patients suffering from a wide range of dermatologic diseases can benefit from the new and exciting therapies and treatment modalities that have recently become available. 

Advice for Clinicians on JAK Inhibitors

Solve the Challenges of Mild to Moderate Psoriasis

AK, SCC Treatments Focus on Efficacy, Tolerability, Durability

Hyperpigmentation Treatment Toolbox

New Indications, Mechanisms Drive Second-Line Treatments

DermView: Innovations in the Treatment of Vitiligo