A presentation from Maui Derm for Dermatologists 2021 virtual dermatology CME conference offered updates on new drugs, research, and expert insights into the management of acne.

The session, Update 2021: Acne and Rosacea, presented live on January 27, was moderated by Guy Webster, MD, PhD, clinical professor of dermatology at Thomas Jefferson University, Lawrence Eichenfield, MD, vice chair of dermatology and chief of pediatric and adolescent dermatology at the University of California San Diego, and James Layton, MD, emeritus professor CE of dermatology at University of Pennsylvania School of Medicine.

Dr. Webster discussed the newest insights from acne research and treatment, featuring discussions on metformin use for polycystic ovary syndrome (PCOS), refracting the notion of spironolactone as a breast cancer risk, and isotretinoin safety, as well as new drugs for acne treatment.

Notably, Webster discussed several studies which found favorable results in treating patients with metformin, including that treatment with metformin alone and in combination with traditional acne medications improves patient outcomes. However, the majority of studies are not completed by dermatologists and investigators have found room to criticize methods.

The presentation relayed studies demonstrating that spironolactone does not increase breast cancer risk or interact with hormonal therapies, nor does it increase the rate of breast cancer recurrence.

New drugs on the market for acne include:

Topical minocycline foam, which works in inflammatory acne

Topical clascoterone, a “soft” androgen blocker

Encapsulated BP + tretinoin, a treatment with minimal irritation and good efficacy

Topical trifarotene, a new fourth-generation retinoid approved for face and trunk

Dr. Eichenfield presented the latest updates in pediatric acne and highlighted the influx of mask-related acne. “I’ve seen a broad set of acneiform and pseudo acneiform eruptions associated with masks,” Eichenfield said.

There has been literature suggesting acne management specific to maskne, Eichenfield said. While the criteria may be helpful, Eichenfield believes that maskne is a mixture of several factors. “Maskne” could potentially be

Regular acne that is more readily noticed,

Exacerbation of acne vulgaris through fabric and microbiome factors

“In general, most of us are managing the acne we see with mask exacerbation as regular acne. But the literature includes antimicrobial cleansers and certainly changes in styles of masks can make a difference,” Eichenfield said.

The session also covered recent acne treatment studies and approvals that have included children. In terms of retinoids, Eichenfield mentioned trifarotene cream 0.005% and tazarotene 0.045%, both of which are approved for patients ages 9 and older; in a pediatric analysis, tazarotene was well-tolerated, with no significant differences in responses between age groups.

Minocycline 4% foam has been approved for non-nodular moderate-to-severe acne for ages 9 and older. The drugs uses molecule stabilizing technology and investigators have not found evidence of phototoxicity, photoallergy, or skin sensitization.

Other new drugs include clascoterone cream 1% and sarecycline, which is taken orally. Moreover, the session mentioned studies focusing on energy-based treatments for active acne and scarring, including blue light and pulsed dye laser (PDL). However, no double-blind, placebo-controlled studies have been completed to date, and much of care is multi-modal, according to Eichenfield.

“I hope in the future, we’ll be able to sort of marry the medical acne care potentially with the procedural acne care, since it tends to be that dermatologic surgeons or laser surgeons who are doing some of the acne, and then most of us who are managing medical acne. So trying to fix it together I think might be appropriate as we try to bring more to our patients across these ages for acne,” Eichenfield said.

Dr. Layton centered his presentation on issues related to isotretinoin treatment, including relapse, acne worsening acute inflammation, sinus tracts, and inflamed keratinous cysts.

“There still are, in my opinion, too many cases of patients getting acutely worse, and sometimes catastrophically worse,” Layton said.

The session reviewed recent research proposing that higher doses could mitigate relapse rates, where age is the most significant factor in retreatment. Layton presented data showing that, in a patient population of over 3000, the number of patients requiring retreatment with isotretinoin was highest in the youngest patients – 10-11 years old – and rates generally decreased with age. Layton also mentioned other factors outside of age, including not taking isotretinoin after a fatty meal, as absorption can be up to 78% lower when fasting occurs.

Maui Derm Live 2021 presentation slides, posters, and other resources can be found 

1. Webster G. Eichenfield E, Layton J, et al. Update 2021: Acne and Rosacea. Presented at: Maui Derm Live. January 25-29, 2021; virtual.

Articles

Maui Derm

A presentation from Maui Derm Live 2021 featured insights on new drugs and data in acne.









2021 Acne Updates: New Drugs and Research

Regenerative aesthetic medicine (RAM) is becoming an increasing popular addition to dermatologists’ practices. Its evolving menu of procedures and applicability in addressing such key concerns as hair restoration, wound healing, scar reduction and anti-aging/rejuvenation address patient demand for natural-looking and longer lasting results.

Mastering the range of modalities is just part of the learning curve in maximizing RAM’s potential. Understanding and complying with relevant regulatory issues is also essential, William P. Weschler, MD, pointed out in his presentation on the topic at Maui Derm Live. The in-person dermatology continuing medical education (CME) conference in Hawaii was held concurrently with Maui Derm Connect, a virtual CME conference, in January.

 features his remarks and comments from an interview in an overview on regenerative medicine to be featured in its April 2021 edition. 

Werschler, an assistant clinical professor at the University of Washington in Spokane, a founding member of Spokane Dermatology Clinic and Werschler Aesthetics, and a 

® editorial advisory board member, cautioned that the premise that, as an autologous procedure, RAM is not subject to FDA oversight is false.

The 21st Century Cures Act signed into law in 2016 addressed RAM. It was designed to accelerate medical product development and bring new innovations and advances to patients who need them faster and more efficiently, and it gave the FDA statutory authority over aspects of RAM by establishing the Regenerative Medicine Advance Therapy program.

But that is just one of the regulatory issues to consider. “RAM procedures and materials do not undergo the traditional process of FDA review and approval as do the drugs, biologics, and devices that we use,” said Werschler. “However, there are FDA guidelines that create guardrails around the conduct of regenerative medicine. Anyone who is using platelet rich plasma (PRP) or stem cells should be fully aware of these rules so that they do not run afoul of the FDA.”

The equipment used in the preparation and administration of the materials—such as the centrifuges used to prepare PRP or the needles, tubing, and syringes used for injection, etc—are FDA-cleared devices, usually class 1 or 2. To date, the FDA has not officially “approved” the autologous use of ADSC or PRP as a medical procedure.

Additionally, under the Public Health Service Act (PHSA) section 361, the FDA has the authority to regulate procedures that may spread communicable diseases. This is intended to minimize infectious disease risks associated with the use of human cells, tissues, and cell- and tissue-based products (HCT/P). Section 361 applies to regenerative aesthetics when the HCT/P is “minimally manipulated and for homologous use only and does not involve the combination of the cells or tissues with another article except for water.”

Section 351of the PHSA is of particular interest to dermatologists who want to offer RAM because it gives the FDA oversight on the use of any HCT/P that are more than minimally manipulated. Essentially, if the regenerative technique does not meet the criteria of section 361, it falls under section 351, which requires a biologics license application.

“When these autologous products are manipulated beyond their original structure and function, they move from just beyond FDA purview to essentially a clinical investigation with institutional review board [IRB] oversight,” Werschler explained. “Physicians are not prohibited from using these techniques, but those who wish to do so must first describe their intent by submitting a study protocol and obtaining IRB approval for the study before they proceed.

“That’s how we learn through the scientific method,” Werschler said.

Expert offers tips on understanding and complying with regulations governing this growing sector.

Quick Guide to Regulatory Issues for Regenerative Aesthetic Medicine

Diagnosis, risk assessment and treatment of congenital melanocytic nevi (CMN), as well as melanoma, require specific strategies for pediatric patients. Elena B. Hawryluk, MD, PhD, assistant professor of dermatology at Harvard Medical School in Boston, Massachusetts, discussed recommendations for understanding how melanoma presents in pediatric cases and how to optimize outcomes during her presentation at Maui Derm Live. Maui Live was an in-person dermatology continuing medical education (CME) conference in Hawaii held concurrently with Maui Derm Connect, a virtual CME conference, from January 25 to January 29, 2021.

Hawryluk first addressed CMN, noting that they increase the risk of melanoma and that the likeliness increases with the papule’s size. For small (<1.5 cm) and medium (1.5- 20 cm) nevi, the risk increases by roughly 1%. For large (>20 cm) and giant (>40 cm) nevi, the risk is 2% for large nevi and 6% to 15% for giant nevi. In CMN-associated melanoma, the risk is highest for patients with giant congenital nevi (78%) with many satellite nevi (94%).

Hawryluk added that atypical or dysplastic nevi, which are not premelanoma, can indicate an increased risk of developing melanoma. Because of this, Hawryluk recommended a thorough examination with continual monitoring.

According to Hawryluk, pediatric patients with large or giant nevi tend to have high mortality (55%), and 14% have visceral melanoma. Hawryluk also noted study results showing that patients with 2 or more nevi have an increased risk of central nervous system involvement, with 21% of patients having abnormal MRI findings.1

Hawryluk explained that various types of melanoma affect the pediatric population and generally present differently than adult patients. A 2013 study advised assessing these lesion characteristics when diagnosing pediatric cases: amelanotic, bump, bleeding, color uniformity, de novo, at any diameter. 

Physicians can often misdiagnose amelanotic melanoma as a benign lesion. Hawryluk cited 2016 study results from the 

Journal of the American Academy of Dermatology 

that found dermatologists, following a first impression, had identified an amelanotic melanoma as a Spitz nevus, hemangioma, and acneiform lesion. To illustrate this point, she shared a case from her practice involving a girl with a suspected wart that hadn’t responded to all typical treatments.

Spitzoid melanoma can harbor kinase fusions in roughly 50% of lesions and can be challenging to diagnose and distinguish from atypical Spitz tumors, in part because nonmelanoma Spitz lesions can also harbor kinase fusions, Hawryluk added.

If there is no suspicion of melanoma, some parents prefer to simply keep the lesions under observation. According to Hawryluk, other choices include surgical excision, although no substantial evidence has been found that the treatment choices reduce the risk of melanoma; curettage; dermabrasion; chemical peels; cryotherapy; laser; and electrotherapy. These treatment options can remove CMN cells, but Hawryluk remarked that they carry the risk of scars or disfigurement and may make it more difficult to detect melanoma.

When considering whether a child needs an MRI, she recommended it for infants with 2 or more nevi, a large axial nevus, the presence of satellites, or older patients who exhibit neurologic changes. She also noted that having imaging from infancy to serve as a baseline can make it easier to discern changes.

For the work-up of patients with CMN and melanoma suspicion, she shared 2 algorithms dependent on whether the presentation was cutaneous or if it was a central nervous system manifestation.

For cutaneous presentations, a thorough clinical examination with photo documentation should occur with a review within 4 weeks. If the new mark is resolved or unchanged, the area should be monitored continually to ensure stability. If the mark progresses or has an abnormal presentation, an excision biopsy should occur, along with histopathology and hotspot genotyping.

If it’s malignant and confirmed by another expert, baseline blood, histology, staging, and further excision should occur as dictated. For new neurological symptoms, imaging should occur. If it’s normal or unchanged from the last imaging session, regular monitoring should continue. For abnormal results, a biopsy followed by histopathology and genotyping may help determine if the result is malignant or nonmalignant.

Hawryluk reported no relevant or financial disclosure.

Hawryluk E. The pigmented lesion clinic: pediatric cases. Presented at: Maui Derm Live In-Person Dermatology CME Conference and Maui Derm Connect Virtual Dermatology CME Conference; January 25-29, 2021; Maui, Hawaii; virtual.

Cordoro KM, Gupta D, Frieden IJ, McCalmont T, Kashani-Sabet M. Pediatric melanoma: results of a large cohort study and proposal for modified ABCD detection criteria for children. 

. 2013;68(6):913-925. doi:10.1016/j. jaad.2012.12.953

Diagnosis, risk assessment and treatment of congenital melanocytic nevi (CMN), as well as melanoma, require specific strategies for pediatric patients.

Optimize Risk, Management of Pigmented Lesions in Pediatric Patients

In a recent extension study of 2 phase 3 clinical trials, a novel 5% encapsulated benzoyl peroxide (E-BPO) cream (Epsolay, Sol-Gel Technologies Ltd) demonstrated significant superiority over vehicle in achieving clear or almost clear skin and reducing the number of lesions in patients with papulopustular rosacea. Data also showed improvement in facial erythema and telangiectasia.

According to study authors, the primary objective of the extension study was safety evaluation. Findings showed the cream was well tolerated with adverse events (AEs) and cutaneous safety and tolerability comparable to the vehicle group.

 Results supported other research that found microencapsulation not only extends drug delivery time but improves efficacy and potently reduces the potential for skin irritation.

“Epsolay uses a patented microencapsulation technology that effectively reduces the risk of skin irritation by encapsulating the BPO inside porous silica microcapsules,” said Neal Bhatia, MD, director of clinical dermatology, Therapeutics Clinical Research, San Diego, California, and lead author of the study. “The capsules form a barrier between the skin and the BPO crystals or other ingredients, allowing for the active drug to be released in a timely fashion, resulting in less skin irritation and a much higher tolerability and amenability of the medication in patients.”

The study results addressed a key challenge; the idea that BPO causes more skin issues. “The phase 3 trials were actually surprising in their outcome because the historical opinion was that BPO was too irritating for rosacea skin, which in the nonencapsulated form is true,” he said.

Philip Werschler, MD,FAAD, FAACS, assistant clinical professor of medicine/dermatology, University of Washington School of Medicine in Seattle, founding member of Spokane Dermatology Clinic, in Spokane, Washington, and coauthor of the study. “The Sol-Gel technology found in Epsolay was very well tolerated and very effective.”

Bhatia and Werschler presented a poster on the study findings at Maui Derm Live. The in-person dermatology continuing medical education (CME) conference in Hawaii was held concurrently with Maui Derm Connect, a virtual CME conference, from January 25 to January 29, 2021.

Patients were followed for up to 40 additional weeks in the extension and for up to a total of 52 weeks, including the 12 weeks in the phase 3 trial.

At each follow-up visit in the extension study occurring at baseline and at 4-week intervals out to week 40, patients were assessed using a 5-point IGA scale of rosacea severity and completed a Rosacea-specific Quality of Life index (RosaQoL) questionnaire. Outcome measures included an Investigator’s Global Assessment (IGA) status of “clear or almost clear”, number and timing of retreatments, and tolerability at 40 weeks. IGA success was defined as achievement of clear or almost clear at the 40-week follow-up visit.

These phase 3 trials (SGT 54-01 and SGT 54-02) evaluated the efficacy, safety, and tolerability of Epsolay in a total of 547 patients, 363 previously treated with Epsolay cream and 184 patients previously treated with vehicle. The study included male and female patients aged at least 18 years with moderate to severe rosacea with a baseline IGA score of 3 (moderate severity) or 4 (severe) on a severity scale of 0-4, between at least 15 and 70 total inflammatory lesions with 2 or fewer nodules present.

Results showed a progressive improvement of rosacea symptoms over the total 52-week study period. At the 40-week follow-up, 67.2% of patients (66.5% in the vehicle group; 67% in the E-BPO group) achieved IGA success. In the extension study, there was an average of 1.4 retreatments with an average of 58 treatment-free days. The investigators also noted that facial erythema generally improved during the study. In addition, results from the RosaQoL questionnaire showed improvements from baseline to week 40 in the total score, symptom subscale score, functional subscale score, and emotional subscale score.

For each of the cutaneous safety and tolerability parameters, data showed small increases in the percentages of patients with no or mild signs and symptoms over 52 weeks. At least 1 treatment-related AE was reported by 185 patients (34.6%), which were mild to moderate in severity and were not considered to be related to the study treatment. Ten patients experienced serious AEs, none of which were considered to be related to the study treatment.

“I think for those patients who have not had a good chance of recovery and good maintenance, Epsolay cream could do well for them because the activity of BPO in the study led to a quicker clearance in patients who applied the product,” Bhatia said.

The FDA is currently evaluating Epsolay, but according to a press release, if approval is passed this spring, Sol-Gel Technologies Ltd projects that the novel formulation has the potential to be the first single-agent BPO prescription drug product.

“This innovative formulation is coming out at a great time because many patients with rosacea have gotten frustrated with their existing therapies that often do not adequately address their symptoms,” Bhatia said. “I think Epsolay cream might be better for patients, particularly because it’s also cream based which might be more amenable to patients.”

Bhatia and Werschler report no relevant or financial disclosures.

1. Bhatia N, Werschler W, Baldwin H, et al. Long-term efficacy and safety of benzoyl peroxide cream, 5%, prepared with microencapsulation in papulopustular rosacea: results from an extension of two phase 3, vehicle-controlled trials. Poster presented at: Maui Derm Live In-Person Dermatology CME Conference and Maui Derm Connect Virtual Dermatology CME Conference; January 25-29, 2021; Maui, Hawaii; Virtual.

2. Erlich M, Arie T, Koifman N, Talmon Y. Structure elucidation of silica-based core-shell microencapsulated drugs for topical applications by cryogenic scanning electron microscopy. J Colloid Interface Sci. 2020;579:778-785.

This formulation could be first FDA-approved single-agent E-BPO prescription drug to treat rosacea. 

New E-BPO Improves Rosacea 

Adequate control of atopic dermatitis (AD) gives patients and their families a new life. A discussion of systemic therapies is definitely warranted for anyone whose disease is not well-controlled using topical therapies, said Eric L. Simpson, MD, MCR, professor of dermatology, Oregon Health & Science University, Portland, Oregon during Maui Derm Live. Maui Live was an in-person dermatology continuing medical education (CME) conference in Hawaii held concurrently with Maui Derm Connect, a virtual CME conference, from January 25 to January 29, 2021.

Simpson discussed his decision-making process for choosing and using systemic treatments for AD and provided an update on dupilumab (Dupixent, Sanofi Genzyme/Regeneron Pharmaceuticals) and forthcoming systemic agents.

“Because of dupilumab’s remarkable efficacy and favorable safety, its approval for the treatment of moderate to severe AD introduced an exciting era for patients needing systemic therapy, and new options are coming, including oral JAK inhibitors that may be just as effective albeit associated with very rare severe adverse events,” said Simpson.

According to Simpson, communication is key when it comes to AD therapy. “Clinicians should be developing their skills for shared decision-making because patients of all ages whose AD is not adequately controlled by topical therapy deserve a discussion of the pros and cons of systemic therapies,” he said.

Simpson said the answer to the question of when to use systemic therapy can be distilled down to 1 concept—it is indicated if aggressive topical therapy is infeasible or has failed to achieve adequate control of the disease.

“A role for systemic therapy is not determined by an AD or itch severity score,” Simpson said. “Rather, it is something to consider and offer patients if moderate- to high-potency topical corticosteroids were used in a safe manner along with topical calcineurin inhibitors or crisaborole and the AD was still not controlled. Also, systemic therapy may be considered as the initial choice for patients whose disease is so severe or so extensive that it requires more than topical therapy.” 

Qualifying his remarks, Simpson pointed out the need to first take a careful patient history to identify any modifiable factors that explain the insufficient response to topical therapy. Communication with patients is also crucial. Issues to explore include whether patients lack an understanding of the chronic nature of their disease and the need for maintenance therapy, if they are following instructions on adjunctive measures such as bathing and moisturization, and if they are using their topical agents properly.

Similarly, once systemic therapy is started, clinicians should carefully review the idea that a particular treatment is not effective or intolerable before it is abandoned, according to Simpson.

“Currently, we do not have many options for systemic treatment, so we don’t want to waste what we have without first making sure that perhaps a longer trial or dose adjustment could improve the therapeutic response or mitigate an adverse event,” he explained.

Simpson also suggested accessing a downloadable, brief patient-reported outcome tool to quickly learn how AD is impacting an individual as this information can help with the decision to start aggressive therapy (adcontroltool.com).

 Then, the consultation conversation should identify the patient’s outcome goals and provide information about the risks and benefits of the available options to support shared decision-making.

According to Simpson, there is no need to consider any particular biomarker or AD phenotype when deciding among available systemic agents.

“Because the Th2 cytokine axis is involved in the pathogenesis of AD regardless of phenotype, Th2 blockade is likely to help almost all patients with AD,” Simpson said.

Corresponding with that idea, results of an Italian study including 221 patients representing 6 phenotypes of AD found significant improvements from baseline to week 16 in all outcomes measured and persistent benefit to week 52.

“The same holds true in my experience,” Simpson said when referring to the study results.

Simpson said he considers cyclosporine if patients need rapid relief or to get off an “oral steroid roller coaster”, if they have failed dupilumab or if the biologic is not covered by insurance, as well as in children aged more than 6 years for whom nothing else is approved when deciding whether or not to use specific systemic therapy. He avoids cyclosporine in older patients on multiple medications and in patients with hypertension or a history of cancer.

“Cyclosporine can be used safely for about 1 year. I use it at a starting dose of 5 mg/kg with tapering over 4 to 12 months while transitioning with overlap to alternative therapy, usually to phototherapy or methotrexate,” Simpson said.

There is another systemic therapy to consider in certain patient populations. According to Simpson, methotrexate is considered for systemic treatment in patients with more moderate AD or for older patients with chronic AD, if dupilumab is not covered, as an add-on to dupilumab, or if he is unsure about the diagnosis. He also uses it in children at a dose of 0.2 to 0.6 mg/kg. Patients with liver disease, women of childbearing potential not using adequate contraception, and anyone who drinks alcohol heavily are not candidates for methotrexate.

Simpson discussed the ease of use of dupilumab compared with the other systemic therapies. According to him, it can be used without laboratory monitoring and is suitable for a long-term approach, including a patient population with viruses.

“I would not use dupilumab during pregnancy, but I see few contraindications for treatment with dupilumab based on medical comorbidities,” he said. “It appears safe to use in HIV-positive patients, and I do not hesitate to use in patients with hepatitis B or C who are on antiviral therapy. Underinsurance is a barrier to its use, as is needle phobia, but there are patient assistance programs for dupilumab, and patients can get over their fear of needles.”

Although there was concern about potential safety issues with the use of biologics and nontargeted immunosuppressive agents at the onset of the coronavirus disease 2019 (COVID-19) pandemic, accumulating experience indicates that these medications do not put patients at risk for a worse outcome and may even have a favorable impact on the disease course.

For example, reports show better outcomes in hospitalized patients receiving cyclosporine compared with patients not on cyclosporine and in kidney transplant patients maintained on a full dose of cyclosporine versus those whose dose was reduced. In vitro evidence that cyclosporine inhibits COVID-19 replication provides a biological basis for these findings.

According to Simpson, regarding dupilumab, dermatology and allergy guidelines state its use should be continued during the pandemic. However, the American Academy of Dermatology recommends stopping biologic treatment if a patient becomes infected with COVID-19. Nevertheless, early evidence from registries show that patients may do better if they are on the biologic, which makes sense because it reduces the cytokine storm, Simpson said.

The latest research results on dupilumab shows that it improves the skin barrier and reduces Th1- and Th2-mediated inflammation and 

 colonization. As another advantage, it is effective in treating allergic comorbidities, including asthma and chronic rhinosinusitis with nasal polyposis.

New data from an open-label extension study of adults treated with dupilumab for moderate to severe AD show responses are sustained and increase overall during ongoing use to 3 years. In addition, the long-term benefit occurs without any new safety signals. In fact, rates of new skin infections and conjunctivitis decreased over time.

The same efficacy and safety patterns are seen during 52 weeks of available follow-up in adolescent patients (aged 12-17) treated with dupilumab. Impressive efficacy was also observed in a 16-week study of school-aged children (6-11 years) whose AD characteristics at baseline were consistent with severe disease. Notably, in the latter trial, the incidence of skin infections was lower in dupilumab-treated groups than in the placebo-treated controls, and the rate of conjunctivitis was lower than what was reported in adults and lower in the study group treated with dupilumab every 4 weeks compared with the group treated every 2 weeks.

Simpson recommends checking the information on the drug’s website when prescribing dupilumab as the dosage regimen for dupilumab in pediatric patients varies depending on weight.

New systemic agents for the treatment of AD are anticipated in 2021, including 1 biologic and 3 oral JAK inhibitors. Based on results achieved in completed phase 3 trials, the oral JAK inhibitors hold promise to be “real game changers” for the treatment of moderate to severe AD, Simpson said.

Overall, the 3 JAK inhibitors investigated in AD pivotal trials provided rapid improvement in overall AD and itch severity ratings, albeit with some distinctions among them in their efficacy and safety profiles.

Of the 3, upadacitinib (Rinvoq, AbbVie Inc) seemed to be the most potent, with 62% of patients treated achieving clear or almost clear status per the Investigators Global Assessment score. However, acne was common (17%) at higher doses of upadacitinib. The efficacy of abrocitinib was comparable if not slightly better than dupilumab, and abrocitinib relieves itch faster. Baricitinib had more modest efficacy but seemed to be the best tolerated of the 3 JAK inhibitors. Compared with abrocitinib, baricitinib was associated with lower rates of headache and nausea.

Simpson has a little apprehension about the 3 therapies.

“My biggest concern with these drugs was a risk of pulmonary embolism that have occurred as rare events with JAK inhibitors,” said Simpson. “Thus far in the AD clinical trials, single cases have been reported with baricitinib and abrocitinib. Nevertheless, all patients on a JAK inhibitor will need risk mitigation for venous thrombosis along with some monitoring of the complete blood count and for herpes zoster virus and herpes simplex virus.”

A new biologic that completed an AD pivotal trial, tralokinumab, is an IL-13 inhibitor. Based on cross-study comparisons with dupilumab, tralokinumab may have slightly lower efficacy with a slower onset, but its benefit may also be longer-lasting, and tralokinumab appears to be associated with a lower rate of conjunctivitis.

“Head-to-head studies are needed to confirm any differences,” Simpson said.

Simpson is a consultant, speaker, and/or investigator for companies that market or are developing products for the treatment of AD.

Comprehensive assessment of atopic dermatitis (AD) control in six brief questions. Atopic Dermatitis Control Tool. Need accessed date. https://www.adcontroltool.com

Tavecchio S, Angileri L, Pozzo GF, Marzano AV, Ferrucci S. Efficacy of dupilumab on different phenotypes of atopic dermatitis: one-year experience of 221 patients. 

. 2020;19(9):2684. doi:10.3390/jcm9092684

The limited armamentarium of systemic therapies for atopic dermatitis has already been expanded with the approval of dupilumab. Forthcoming systemic therapies are expected to include a new biologic and three new Janus kinase (JAK) inhibitors. 

Systemic Therapy Advances for AD

Recent research on the importance of phenotype classification, comorbidities, triggers, and mechanism of action—including possible implications for metainflammation in coronavirus disease 2019 (COVID-19)—can expand the understanding of rosacea and suggests new directions for diagnosis and prognosis of this widespread skin disease.

Richard Gallo, MD, PhD, chair of the department of dermatology at the University of California San Diego (UCSD), provided an overview of current trends advancing rosacea therapy in his presentation at Maui Derm Live. The in-person dermatology continuing medical education (CME) conference in Hawaii was held concurrently with Maui Derm Connect, a virtual CME conference, from January 25 to January 29, 2021.

His remarks were featured in the session, “Update 2021: Acne and Rosacea”, which highlighted new drugs, research, and expert insights into the management of rosacea and acne. Guy Webster, MD, PhD, clinical professor of Dermatology at Thomas Jefferson University, Philadelphia, Pennsylvania, moderated the panel which included speakers Lawrence Eichenfield, MD, vice chair of Dermatology and chief of Pediatric and Adolescent Dermatology at UCSD, and James Leyden, MD, emeritus professor CE of Dermatology at University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania.

Gallo outlined 4 key areas driving change in addressing the challenges of rosacea.

“Rosacea is now understood by phenotypes,” Gallo said. These phenotypes are (1) diagnostic: fixed centrofacial erythema in a characteristic pattern that may intensify periodically or phymatous changes; (2) major: flushing, papules and pustules, telangiectasia, and ocular manifestations; and (3) secondary: burning sensation; stinging sensation; edema; dryness and ocular manifestations.

Gallo stressed the importance of using the phenotype-based classification system for rosacea rather than the subset-based method. Gallo noted limitations in describing a patient’s rosacea through subsets. Often, patients experience many subtypes simultaneously. Categorizing by phenotype allows health care professionals to track patient progress.

“Studies from 2020 confirmed a growing number of rosacea comorbidities including those related to cardiovascular, neurologic, and gastrointestinal risks,” said Gallo. Two meta-analyses found that patients with rosacea have a higher risk of hypertension, CRP, high LDL, epicardial fat, and insulin resistance, Gallo pointed out. According to 8 recent studies that evaluated a total of 200,000 patients, individuals who have rosacea also have an increased risk of migraine, Parkinson disease, and depression. Several studies pointed to higher risks of inflammatory bowel disease.

That is not all. “Innate immune dysfunction drives rosacea’s comorbidities,” said Gallo.

Ultraviolet (UV) light releases potential trigger molecules such a nucleic acids and other damage-associated molecular patterns. Although these endogenous danger molecules released from damaged or dying cells activate the innate immune system by interacting with pattern recognition receptors, they may also promote pathological inflammatory responses.

The cathelicidin peptide LL-37 is another factor. “LL-37 facilitates DNA recognition but does that explain UV sensitivity in patients with rosacea?” asked Gallo. In a study published last year, Gallo and his fellow authors saw results showing that LL-37 amplifies the response to UV products and predicts vascular cell adhesion molecule response in rosacea.

According to Gallo, research on rosacea’s mechanism of action could hold promise for better understanding COVID-19. Mutation scanning identified a possible structure necessary for inflammatory activity relating to COVID-19.”

Gallo is a co-founder and holds equity interest in MatriSys Bioscience and is a consultant for Sente Inc.

Webster G. Eichenfield E, Layton J, et al. Update 2021: acne and rosacea. Pre- sented at: Maui Derm For Dermatologists 2021; January 25-29, 2021; Maui, Hawaii.

Gallo R, Granstein R, Kang et al. Standard classification and pathophysiology of rosacea: The 2017 update by the National Rosacea Society Expert Committee. J Am Acad Dermatol. 2018;1(78):148-155. doi:10.1016/j.jaad.2017.08.037

Kulkarni NN, Takahashi T, Sanford JA, et al. Innate immune dysfunction in rosa- cea promotes photosensitivity and vascular adhesion molecule expression. J Invest Dermatol. 2020;40(3):645-655.e6. doi:10.1016/j.jid.2019.08.436

Update tracks trending factors changing the treatment landscape. 

New Research Addresses Rosacea Challenges 

Simply observing symptoms can often help a patient receive a hair loss disorder diagnosis. However, observation alone is less helpful in evaluating treatment methods.

“It is important for a dermatologist to be able to quantify how much hair has been lost or gained,” said Jerry Shapiro, MD, a professor of dermatology at the NYU Grossman School of Medicine, New York, New York, who spoke on managing hair loss disorders at Maui Derm Live.

 The in-person dermatology continuing medical education (CME) conference in Hawaii was held concurrently with Maui Derm Connect, a virtual CME conference, January 25-29, 2021.

“Because of the tools now available to quantify, we now have a more scientific approach to determine how much [hair] gain or loss the patient has had from their treatment protocol.”

Trichometrics/numerics are key to measuring the efficacy of treatment modalities for hair growth. The 3 devices most effective to confirm success or failure in the office setting, according to Shapiro, are the Folliscope (LeadM Corporation), FotoFinder (FotoFinder Systems), and artificial intelligence with Vectra (Canfield Scientific Inc.).

“These are easy and accurate devices to use,” Shapiro told 

. “Patients also appreciate them because they like to know their numbers and whether those numbers have gone up or down or are the same.”

Scarring alopecias are a group of disorders characterized by a final common pathway of replacement of follicular structure by fibrous tissue. They present clinically as loss of follicular ostia and the histopathology is obliteration of the hair follicle.

“There are no placebo-controlled, double-blinded, randomized studies of therapeutics for scarring alopecias, and no evidence-based medicine,” Shapiro said.

One of these conditions is primary cicatricial alopecia, which involves preferential destruction of follicular epithelium with sparing of interfollicular dermis. Clinical indications are hyperkeratosis, erythema, a positive pull test, and symptoms includes itching, burning, and pain.

Discoid lupus erythematosus, another type of scarring alopecia, presents with lesions often localized to the scalp and can be treated based on the extent of disease. For milder cases, an ultra-potent topical steroid might be combined with intralesional triamcinolone acetonide (IL-TAC). If improvement occurs, treatment can continue as needed. But with no improvement, 3 other options are hydroxychloroquine, isotretinoin, and topical tacrolimus 0.3% twice a day+ corticosteroid twice a day + 5% minoxidil solution twice a day (TCM).

For more severe forms, beginning therapy comprises hydroxychloroquine 200 milligram (mg) twice a day, along with perhaps an ultra-potent topical steroid and/or IL-TAC and/or prednisone. With improvement, medications can be tapered to the lowest effective doses.

Assessment of clinical features of classic lichen planopilaris, a third type of scarring alopecia, may be enhanced through trichoscopy. Erythema and hyperketatosis can also be quantified and hair density quantified at target areas.

However, because of the risk of koebnerization with classic lichen planopilaris, “a hair transplant should be considered only after at least 2 years have passed with no disease activity,” Shapiro said. For rapidly progressive disease, oral prednisone can be given tapered for the first 8 weeks to bridge therapy.

Milder cases of classic lichen planopilaris can be stabilized with a treatment regimen of IL-TAC 10 mg/ml monthly + TCM twice a day. Treatment may continue as needed.

For more severe disease, a regimen of IL-TAC 10 mg/ml monthly + TCM twice a day + doxycycline 100 mg twice a day or hydroxychloroquine 200 mg twice a day is appropriate.

An increasingly common hair-loss condition is frontal fibrosing alopecia (FFA), which is irreversible and a trichologic emergency that requires immediate attention. “We do not know why we are seeing so many more cases,” Shapiro said. “Fortunately, there are treatments that can halt FFA by creating follicular rescue, so that no more hairs are lost.”

Aggressive management of FFA is necessary, including cortisone injections, topical tacrolimus, cortisone lotions, topical minoxidil, doxycycline, hydroxychloroquine, pioglitazone (Actos, Takeda Pharmaceuticals), and low-dose naltrexone. Finasteride or dutasteride, types of 5-alpha-reductase inhibitors, may also be used.

“Patients can start seeing a positive effect usually in 3 months,” Shapiro said. “There is also a low likelihood of [adverse] effects.”

Platelet rich plasma (PRP) is an adjunctive modality for treating androgenetic hair loss or alopecia areata. “Patients usually need 3 treatment sessions, spaced 1 month apart, followed by a hair count to determine if they have improved,” Shapiro said. “Photographs may not be sufficient to quantify the amount of improvement, so meticulous quantification is key to PRP treatments.”

Therapy can continue as long as improvement is observed. However, 2 downsides of PRP are pain and expense for some patients.

A game changer for managing alopecia areata is the use of oral Janus kinase (JAK) inhibitors, according to Shapiro. “They can also be used to treat certain forms of scarring hair loss,” he said. “Overall, JAK inhibitors have the highest chance of success for alopecia totalis or universalis.”

Shapiro favors the JAK inhibitor tofacitinib at a dose of 5 mg, twice a day. Newer JAK inhibitors, such as baricitinib (Olumiant, Eli Lilly and Company), have also proven to be effective.

“Patients, though, need to be monitored for [adverse] effects; namely the immune system through a complete metabolic panel, a complete blood count, and testing of triglyceride and cholesterol levels,” Shapiro said.

Women who use an intrauterine device (IUD) containing hormones/levonorgesterol are at risk of significant telogen effluvium upon insertion or removal.

Future therapies being developed for follicle neogenesis include an autologous dermal sheath cup, dermal papilla cell injections into the scalp, and hair farming/cloning.

Shapiro is a consultant/investigator for the following companies: Samumed, Incyte, Applied Biology, Eirion Therapeutics, RepliCel Life Sciences, Regen Lab SA, Keeps.com, Cassiopea, Pfizer, and Almirall. He also is an investigator for the non-approved uses of the medications naltrexone and pioglitazone.

Shapiro J. Maui Derm 2021. Dr. Jerry Shapiro Discusses The Management of Hair Loss Disorders in 2021. Presented at Maui Derm Live, January 25-29, 2021. Maui, Hawaii.

Trichometric analysis helps evaluate whether treatment is working for patients experiencing hair loss and what adjustments need to be made to the regimen.

Quantifying is Key to Effective Hair Loss Treatment

A result of the first major overhaul in 25 years, the 2021 

) code set published by the American Medical Association (AMA) incorporated foundational changes that ease evaluation and management (E/M).

Wholesale changes to CPT E/M coding that took effect January 1, 2021, streamline billing documentation for dermatologists,” said Mark D. Kaufmann, MD, chief medical officer at Advanced Dermatology and Cosmetic Surgery in Maitland, Florida, in his presentation at Maui Derm Live. The in-person dermatology continuing medical education (CME) conference in Hawaii was held concurrently with Maui Derm Connect, a virtual CME conference, January 25 to January 29, 2021.

Table – CPT E/M Office Revisions Level of Medical Decision Making (Courtesy of the American Medical Association)

These changes would result in a shift in billing patterns for dermatologists, Kaufmann added. He likened the new 5-column grid1 used for coding E/M services to the Bible stating that, “This is the guidance that the AMA has given us—a 1-page graphic with language that is broadly open to interpretation.”

 Kaufmann is also clinical associate professor of the Department of Dermatology at the Icahn School of Medicine at Mount Sinai New York and an advisor to the American Academy of Dermatology Relative Value Scale Update Committee.

Dermatologists must use information from 2 of the 3 medical decision-making (MDM) columns in the code set to support the codes they bill, Kaufmann said. For example, androgenetic alopecia automatically merits a moderate (level 4) degree of MDM because it is a chronic condition that progresses. Dermatologists can choose level 4 in the first MDM column, Number and Complexity of Problems Addressed.

According to Kaufmann, a dermatologist prescribing a medication such as finasteride for androgenic alopecia can document this activity in the third MDM column, Risk of Complications and/or Morbidity or Mortality of Patient Management. With this example of moderate MDM in column 3, the dermatologist should have “moderate” in columns 1 and 3. Accordingly, the dermatologist could code the visit at 99204 or 99214, he says.

If the physician recommends an OTC medication such as minoxidil, this qualifies for low- level MDM, making the visit level 3 instead of 4. Counseling a patient without recommending treatment represents a straightforward MDM, a level 2 visit.

According to Kaufmann, medical dermatologists will “live” primarily at the low and moderate levels. Among the MDM columns, there will be appropriate occasions for column 2, such as when Mohs surgeons undertake patient consultations known as Amount and/or Complexity of Data to be Reviewed and Analyzed. “But in general dermatology, I have found that if you’re looking to get to a moderate level of MDM, a level 4 visit in column 2, you’re probably already there with columns 1 and 3,” he noted.

Risk levels associated with specific treatments require interpretation, Kaufmann said. For example, prescription drug management (an intervention option in the third column) corresponds with a moderate risk level. “Prescription drug management is a very broad statement,” he said. “In this regard, the AMA has said that even if a physician discusses a systemic drug with a patient and the patient refuses the drug, that’s prescription drug management. You don’t have to write the prescription. On the flip side, you have to decide where you sit when a patient says, ‘I need the same triamcinolone prescription you gave me last year for my winter’s itch.’”

Dermatologists must determine whether they are comfortable calling this interaction prescription drug management for billing purposes. “Everyone has to define the lines in their own minds," he said. "In my opinion, when patients come in for refills of systemic drugs, that’s always prescription drug management because you’re going to be talking about the drug with the patient.”

In Kaufmann’s view, financial implications of the E/M changes are likely to provoke payer anxiety. Initially, the Centers for Medicare & Medicaid Services (CMS) estimated that the changes’ net impact would be neutral or even feature a 1% cost reduction. The stimulus package signed by President Donald Trump in December 2020 turned the expected impact into a 5% cost increase.

The boost is helpful for 2021, according to Kaufmann. “But that doesn’t do anything for us in 2022 and beyond,” he said. “I’m sure that many of us will go to Capitol Hill later this year with the American Academy of Dermatology and other groups to ask that this fix be extended. But there’s no guarantee that it will be. And next year, we may be in the same position we were prior to the stimulus bill being signed.”

CMS’ cost estimates rested on the expectation that in 2021, the number of codes used at each level would remain the same as in 2020, but 99201 was eliminated. More importantly, Kaufmann expects 99202 usage to decline this year because many of these visits will shift to 99203. “I believe that many of the 99203s will shift to 99204, which was hardly perceptible up until January 2021,” he noted.

According to Kaufmann, CMS did not consider those dynamics when formulating their predictions. “We are probably going to see more audits,” he said, “which may lead to further deliberations on how to deal with these new realities.”

Kaufmann is adviser to the American Association of Dermatology RVS Update Committee. He also owns stock in Modernizing Medicine and stock options in Klara.

1. CPT evaluation and management (E/M) office or other outpatient (99202- 99215) and prolonged services (99354, 99355, 99356, 99XXX) code and guideline changes. September 1, 2020. Accessed January 26, 2021. https:// www.ama-assn.org/system/files/2019-06/cpt-office-prolonged-svs-code-changes.pdf

2. Kaufmann MD. How to maximize your billing effectiveness in the era of dwindling reimbursements and ICD-10. Presented at: Maui Derm For Dermatologists 2021; January 25-29, 2021; Maui, Hawaii.

This is the first overhaul in a quarter century that simplifies evaluation and management and increases flexibility.

AMA Streamlines Billing CPT Codes

Trichoscopy (a dermoscopy-based diagnostic method) not only helps diagnose hair disorders and monitor treatment but also predicts treatment efficacy, Anna Waśkiel-Burnat, MD, PhD, a dermatologist at Medical University of Warsaw in Poland, said at the 29th European Academy of Dermatology and Venereology Virtual Congress.

“There are numerous hair and scalp diseases that share similar clinical features,” Waśkiel-Burnat said in her presentation. “Trichoscopy is an easy-to-perform diagnostic method that may help identify subtle details and establish the correct diagnosis. For example, it is difficult to distinguish between female androgenetic alopecia [FAGA] and fibrosing alopecia in a pattern distribution [FAPD] based only on the clinical picture. In these conditions, trichoscopy is useful to avoid misdiagnosis.”

Features of FAGA include increased numbers of vellus hairs and single-hair follicular units, along with anisotrichosis and yellow dots. For a diagnosis of FAGA, patients must meet 2 of the following major criteria

More than 4 yellow dots in 4 images at 70-fold magnification in the frontal area

Lower average hair thickness in the frontal area compared with the occiput (calculated from at least 50 hairs from each area).

More than 10% thin hairs (< 0.03 mm) in the frontal area

Alternatively, dermatologists can establish a diagnosis of FAGA using 1 major criterion and 2 of the following minor criteria (all comparing frontal area with occiput):

3.1 ratio of hair follicles with perifollicular discoloration

“Another condition that is difficult to diagnose, even with trichoscopy, is alopecia areata [AA] incognita,” Waśkiel-Burnat said. Because this entity is frequently misdiagnosed as telogen effluvium, histopathological examination is important, she said.

Because it is challenging to identify patients with AA who are at risk of rapid disease progression and to determine which patients are likely to respond well to immunosuppressive therapy, Waśkiel-Burnat and colleagues developed the Alopecia Areata Predictive Score.

According to one expert at the 29th European Academy of Dermatology and Venereology Virtual Congress, trichoscopy (a dermoscopy-based diagnostic method) not only helps diagnose hair disorders and monitor treatment but also predicts treatment efficacy.

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