Need-to-know updates featured in articles, news briefs, podcasts, and videos keep everyone in the dermatology community in the vanguard of the effort to put a cure for melanoma within reach.

Melanoma Awareness Month

Acne Awareness Month

This online, on-demand virtual symposium brings together renowned experts in dermatology to discuss newer treatments for patients with psoriasis.

Maui Derm Tyk2 Psoriasis Archived Webcast

Patients with this rare and severe skin disorder may soon have a new therapeutic option.

Perspectives on Generalized Pustular Psoriasis

 Let’s change gears and talk about the burden of the disease on patients and quality of life. Lisa, I’m going to turn this over to you. Talk to us about how atopic dermatitis affects the quality of life of patients and their families.

 It does so in a huge way. A lot of the quality-of-life impact boils down to a couple of main things. Itch is the most burdensome symptom of atopic dermatitis. Patients itch until they bleed because the pain is better than the itch. The itch is a major burden that they deal with on a daily basis. Because of the itch, sleep is disturbed. Sleep is disturbed for not only the patient but also their family members. If it’s a child with atopic dermatitis, it results in loss of sleep for the parents. If it’s an adult with atopic dermatitis, it probably results in loss of sleep for their partner. The issue with sleep disturbance is a big one that wreaks havoc on a patient’s quality of life and the quality of life of their family members.

The other thing is that atopic dermatitis can sometimes result in a slow creep of worsening over years. Sometimes patients and their families might not fully understand the burden it’s having on them until they go on therapy or a treatment plan that makes them better. There’s the expression, “You can boil to death in a slowly heating bathtub.” For some patients, the atopic dermatitis is the slowly heating bathtub. When they finally go on a therapy that helps them, they think, “My gosh, I can’t believe I was suffering so much before.” Sometimes they don’t realize that impact until it gets better for them.

 I see that all the time. People accept it and can’t imagine their life being any different. Then when you get them on a therapy, like a systemic biologic for atopic dermatitis, they can’t believe the difference.

 Definitely. The other thing that our patients with atopic dermatitis have to deal with are comorbidities. Atopic comorbidities include asthma, allergies, and eosinophilic esophagitis. There have eye comorbidities, such as keratoconus, conjunctivitis, and blepharitis. There have been recent studies linking increased risk of cardiovascular disease. We have increased risk of growth issues, osteoporosis, osteopenia, fractures, anxiety, depression, ADHD [attention-deficit/hyperactivity disorder], and learning disabilities. All these comorbidities have been well established in our literature and are a big reason for us to take atopic dermatitis seriously and advocate to make it better for our patients and their families.

We talk about adverse effects of potential therapies. That’s appropriate, but these comorbidities are the adverse effects of not controlling the atopic dermatitis. It’s important to emphasize that we now have tools in our toolbox that can make this better for them. It’s not all about topical steroids anymore. It’s important to encourage families to take control of their atopic dermatitis and let us help them make it better.

 That’s great. Like so many other dermatologic conditions, atopic dermatitis is much more than skin deep, and getting early effective treatments has such a profound impact on quality of life in general.

Videos

Expert pediatric dermatologists Elizabeth Swanson, MD, and Joshua Zeichner, MD, discuss the burden of pediatric atopic dermatitis.

Burden of Atopic Dermatitis in Pediatric Patients

Let’s talk about the presentation of atopic dermatitis [AD]. It presents a little differently depending on the age of the patients. Brit, tell us a little about this.

Traditionally, we learned that atopic dermatitis is red, oozy, scaly, and dry—and a lot of times it is—but it’s important to understand that it can look very different in different people. Classically in infants, it’s going to be more extensor surface–heavy on the face, those stoplight red cheeks that you get. Then as kids get a little older and start to walk, it switches to more of that adult presentation, where you have the antecubital fossa and popliteal fossa heavily involved. Many patients are going to be very red, dry, and crusty. But especially in patients with darker skin types, it’s important to note that it doesn’t always look like that. Sometimes from the door, you might not even be able to recognize it. But when you get up close, you’ll see that the patient might be covered in follicular-based papules or have more of a prurigo nodularis type of presentation.

Another important point is that patients with AD have inflammation, even when you don’t necessarily see anything on their skin. Sometimes parents will say, “Her skin looks pretty good, but she’s still itchy all the time.” Our assessment of the patient isn’t about only what we see. It’s about their experience with the disease. Every so often, residents will tell me, “The patient is here for atopic dermatitis. It doesn’t look that bad.” And I say, “It doesn’t look that bad to you? Or it doesn’t look that bad to them?” We have to remind ourselves that we see this spectrum. We see a patient who’s erythrodermic, but that doesn’t mean that the patient who just has the antecubes and popliteal fossae isn’t having a big impact on their quality of life. It can look different in different people. Understanding the patient experience and the itch is huge. That can help drive our treatment more so than what we see.

I’m so glad that you brought up those 2 points. I want to highlight that a little more. No. 1 is skin of color. For so long, we’ve seen photos of atopic dermatitis in White patients, and we need to recognize the different clinical presentations that we see in skin of color. Whether we’re talking about African American patients, Asian patients, or South Asian patients, we need to recognize that not all atopic dermatitis looks the same.

The other point that I love that you brought up is patient experience. When we talk to our patients, we can’t make assumptions about how much it impacts their quality of life based on what we’re seeing. You always need to have open-ended conversations with patients, asking them, “Was today a good day? Is today a bad day or an average day? How is this affecting you?” You can’t quantify itch based on the severity of the lesions that you’re seeing on the skin.

We have to remind ourselves that we sometimes catch them on a good day, but even on a good day, many patients are worried about their next flare. The chronicity of the disease and the ebb and flow is difficult physically and psychologically. Finding out where they’ve been over the last several months since we’ve seen them is more important than where they are at that moment in time.

This bridges nicely to my next question, which is the way that you guys clinically assess your patients with atopic dermatitis and make the diagnosis. Raj, let me turn this over to you.

 I’m happy to wax poetic on this one. The most important thing to think about is the heterogeneity of disease. That’s one of the things I love talking about regarding atopic dermatitis. The burden and presentation varies so much from person to person that we’ve tried to boil it down to anchoring on 1 specific thing we’re looking for when it comes to making assessments of severity. But in reality, there are a lot of things going into this calculation.

To take a step back, in terms of diagnosis, a lot of times people come to the clinic, and your gut tells you based on the story and what you’re seeing that this is probably atopic dermatitis. But atopic dermatitis is officially a clinically diagnosed disease. There are a couple of different systems for diagnosis. There isn’t 1 specific system that’s used quite a bit, but the first codified one was the Hanifin and Rajka criteria. Typically, you’re using a series of major and minor criteria.

In practice, most people aren’t doing this, but for the audience today, typically what you’re looking for is pruritus and some type of typical morphology or distribution. This includes lichenification or linearity in adults, facial extensor involvement in infants and children, typically a chronic relapsing dermatitis, and a personal family history of acne. Then there’s a number of minor criteria you can go for. People have tried to shorten this up over years and make easier, more clinically relevant criteria. A common one you’ll see a lot in the literature is the UK Working Party’s Diagnostic Criteria for Atopic Dermatitis. This is where people are saying someone has to have an itchy skin condition and then a couple of other small factors: things like flexure involvement, a history of atopy, and generalized dry skin.

From a practical standpoint, the AAD, the American Academy of Dermatology, largely recommends that you’re talking about some type of dermatitis condition and chronic itch, and then you put the pieces together. There are a lot of ways to look at it. But once you’ve made the diagnosis, when it comes to figuring out, “Is this mild? Is this moderate? Is this severe?” Oftentimes we’re anchoring on the extent. What’s the body surface area? But that’s just 1 aspect of disease that doesn’t perfectly correlate.

There are measures of lesion severity. Oftentimes people use gestalt or Investigator’s Global Assessments to rank someone as mild, moderate, or severe, but that’s usually looking at a very small defined area. People forget that there are lots of different morphologies, topographic distributions, comorbid burdens, and quality-of-life effects. There are different responses to previous medications. There are huge differences in longitudinal course when it relates to the disease. I like to think about all of those in context together when I’m trying to assess severity rather than boiling it down to only 1 specific aspect.

Are there any pearls that you have on specific ways atopic dermatitis presents in different skin types?

 That’s a huge one that Brittany very nicely started bringing up in our previous discussion. I’m happy to continue along. One big question people always ask is: “If you aren’t used to looking at different types of skin pigmentation and if erythema is such an important component of what you’re looking for, how do you best measure severity using the tools we have?” Redness can look like a variety of things. It can look brown, purplish, like hyperpigmentation, violaceous—you name it. They’re all ways to get at inflammation. That’s 1 challenge that can occur from skin type to skin type.

The other thing I’ll bring up is that there are different types of lesions that all fall under the atopic dermatitis umbrella. If you were to ask someone about atopic dermatitis, they’d say, “Inside the elbows, back of the knees, flexural areas, done deal.” But if you look at a nice systematic review and meta-analysis of lesion findings all across the world, more than half of people reported flexural issues, but what was the second thing on that list? Extensor dermatitis. We think of that as being related to psoriasis, not even eczema, but that’s an important part of the disease. Other things on that list include prurigo nodules, which are important; lichenoid papules, oftentimes on the backs of the hands; and perifollicular papules, oftentimes widespread across the surface of the skin. It's hard to see and easier to pick up when you’re touching the skin. Interestingly, even though they look very different from one another, these are all different manifestations of the same disease.

Brittany Craiglow, MD; Raj Chovatiya, MD, PhD; and Joshua Zeichner, MD, discuss the presentation of pediatric patients with atopic dermatitis and how to properly assess and diagnose pediatric patients’ atopic dermatitis.

Presentation and Diagnosis of Atopic Dermatitis in Pediatrics

Let’s change gears and talk about the psychological factors impacting atopic dermatitis. Lisa, I’m going to ask you to take this one.

 Thank you so much, Josh. Psychological factors play a big role with atopic dermatitis. The biggest one, of course, is stress. When patients are under stress, often their atopic dermatitis gets worse. That can turn into a bit of a vicious cycle because the stress creates a flare of their atopic dermatitis, which stresses them out even more. They go round and round, and their atopic dermatitis flares up. These psychological factors—a lot of which are outside our control, including COVID-19 stressors, school stressors, and family stressors—can drive the disease.

We see stress as a significant factor in atopic dermatitis and a lot of other conditions in dermatology, whether it’s rosacea, psoriasis, or acne. We can’t underestimate the impact that stress has on the quality of life of the patients who are suffering and their support network: their parents, friends, and teachers. We want to get the disease under control for the whole community.

Elizabeth Swanson, MD, and Joshua Zeichner, MD, discuss the psychological factors impacting pediatric patients’ atopic dermatitis.

Psychological Impact of Atopic Dermatitis in Pediatric Patients

As we’ve developed a better understanding of the pathophysiology of atopic dermatitis, we’ve also had a flood of new medications that are more specifically targeted to treat atopic dermatitis. Raj, talk to us a little about this.

 Sure. Vikash Oza laid down the important aspects we think about when it comes to immunologic dysregulation with atopic dermatitis. But very broadly, I like to think about the pathophysiology of the disease in 2 major buckets. We think about barrier dysfunction and immune dysregulation. Most of our therapeutic armamentarium and stepwise therapy that we follow, no matter what guidelines you’re using, are addressing some aspect of that disease. That way, you can think about atopic dermatitis having both outside-in and inside-out mechanisms. What do we mean by that? There are different types of genetic mutations and polymorphisms related to the immune system and the barrier that can cause various cycles of inflammation to start up, leading to atopic dermatitis. We also know there are external perturbations in the environment when it comes to toxic substances, allergens, and irritants that can interact with the barrier, causing further perturbation and inflammation. It’s a chicken-or-egg question, and both probably apply here. People oftentimes like to choose 1 camp or the other, but both are happening at any given time.

When you think about our stepwise approach to therapy, at the base, we’re always trying to optimize barriers. That’s dealing with the 1 big pillar we talked about: barriers. That’s any time you’re using an emollient or trying to avoid a specific irritant that you have on the skin. You could optimize bathing. That’s exactly what you’re doing. The next step up when you’re thinking about anti-inflammatory therapy, typically in a topical form, is where you’re starting to address the immune dysregulation that I talked about. For many years, topical corticosteroids, which are broadly acting across a number of different cells—T cells in particular, but others as well—is largely turning down immune activity in a broader fashion. There’s been evolution in topical therapy slowly over years. Topical calcineurin inhibitors was 1 step forward. These are going to be working mainly on T cells in a slightly more targeted but still pretty broad fashion.

Several years ago, we had the approval of the first phosphodiesterase-4 inhibitor. This is a bit more targeted in terms of therapy. This is going to change cytokine signaling and reduce inflammation through a different route. Most recently, we had a topical JAK inhibitor approved for mild to moderate atopic dermatitis. This is going to specifically target an intracellular signaling pathway that’s important for a lot of different cytokines.

Moving into more of a systemic therapy route, in terms of an injectable and an oral therapy route, we have biologic therapies that Vikash eloquently told us about in the case of dupilumab. Tralokinumab is another one out there. We have a bunch of others coming. These variably target other important cytokines when we think about the type 2 inflammatory cascade, so IL-4 and IL-13. There’s development for other aspects of disease, including IL-31. You’re going to hear more about OX40 ligand and other various signals on that route.

Finally, in terms of the JAK inhibitors, the most recently approved class, these are very different from biologic therapies. Biologic therapies are antibody-based proteins that are going to bind to signals outside the cell, whereas JAK inhibitors are small molecules that are going to be working inside the cell on the JAK/STAT signaling pathway. They’re working broadly across a number of cytokine pathways. Very broadly, we understood that the barrier and immune system were important. But as we’ve come to understand how important immune system activity is, we’ve had a huge boom in a lot of our targeted and safer therapies for atopic dermatitis.

It’s so interesting. I tend to look at these therapies as upstream or downstream. The more traditional or older therapies were more upstream. They addressed inflammation early on and more broadly. As a result, they had a lot more potential adverse effects. As we understand the pathophysiology and we have more targeted therapies, we have medications that address things more downstream. They’re a bit more focused and perhaps a bit safer, with fewer generalized adverse effects.

 That’s a good way to think about it. Both therapies have some merit. If we’re going to use psoriasis as an example, think about the third and fourth generation of biologic therapies. You have IL-17, the most downstream in the psoriasis pathway, and IL-23 extremely upstream in terms of Th17 differentiation. Both are extremely effective and work really well on disease. To your point, as we develop more targeted therapies, I bet we’re going to find different ways to inhibit things both early on and later on, arriving at perhaps the same point.

Joshua Zeichner, MD, and Raj Chovatiya, MD, PhD, dive deep into the pathogenesis of atopic dermatitis and discuss how agents treating atopic dermatitis work.

Mechanism of Action for Agents Used to Treat Pediatric Atopic Dermatitis

Hello, and thank you for joining us for this 

 series. I’m Dr Joshua Zeichner. I’m an associate professor of dermatology and the director of cosmetic and clinical research in dermatology at Mount Sinai Hospital in New York, New York. In this series, I’ll be moderating a panel discussion and a case study review on new directions in the management of atopic dermatitis.

Joining us are Dr Brittany Craiglow, a dermatologist at the Dermatology Physicians of Connecticut and an adjunct associate professor at Yale School of Medicine in New Haven, Connecticut; Dr Lisa Swanson, a pediatric dermatologist at St. Luke’s Health System in Meridian, Idaho; Dr Vikash Oza, the director of pediatric dermatology at NYU Langone Health and an associate professor of dermatology and pediatrics at the NYU Grossman School of Medicine; and Dr Raj Chovatiya, an assistant professor of dermatology at Northwestern University Feinberg School of Medicine in Chicago, Illinois. Welcome, everybody.

In addition to discussing the newest updates in the field, we’ll also be exploring 3 patient cases. Let’s get started. Let’s start by talking about the characteristics of type 2 inflammation. What’s the role of cytokines in the development of inflammation in atopic dermatitis? Vikash, tell us about this.

 As with any inflammatory disorders, the specific types of cytokines play a large role. A lot of times we parallel atopic dermatitis with psoriasis, and we’ve learned with all these new biological therapies in psoriasis that having a target for specific cytokines can make a huge impact on disease control. That’s true in eczema. We think of eczema as this classical type 2 inflammatory disorder, so certain key cytokines play a large role in driving the disease state. We know about the type 2 specific ones, IL-4 and IL-13, with specific interest in IL-13 playing a large role in atopic control. Now that Dupixent [dupilumab] has been out for a while, we’ve learned how targeting those cytokines can make a huge difference in terms of the disease state.

It’s also true that when we look at different patient populations, we see Th2 and Th22 upregulated in young children, profiles of Th1 in older patients, and Th17 in East Asian patients. There are variations in the immunologic profile across ethnic groups and age, but at the core, we still see an important role that Th2 cytokines play because we know that dupilumab is pretty effective across that group. Even though we learn about different signatures and immune pathways, there’s a lot of crosstalk, and they don’t exist in silos. It has been the advancement of our basic science understanding of the immunopathogenesis that has helped drive this flood of new potential therapies that we have coming to the clinic.

It’s so interesting that aside from the type 2 cytokines being involved in the inflammation that we see, there are also structural changes in the stratum corneum and skin barrier. Talk to us about that a little.

 We see a tight interplay between so many elements, whether we’re talking about our lipid bilayer and how successful we are in controlling trans epidermal water loss. When we downregulate the inflammatory pathways, we see recovery of that. When we’re talking about the microbiome, which is so critical in atopic dermatitis pathogenesis, and the colonization of staph aureus, targeting those inflammatory cytokines help recuperate a more diverse microbiome. There’s a very tight interplay between the complex biology of the bilayer as well as our microbiome and the inflammatory cascade that lies underneath.

What about itch? Itch is a huge issue in atopic and nonatopic patients, but we know that eczema-related itch is different from other types. Talk to us a little about type 2 cytokines and eczema-related itch.

 There are certain cytokines that play an important role in driving itch, with IL-31 being 1 of them. In clinical trials, we have agents targeting IL-31 to help reduce itch. Certain therapies may help reduce itch quicker. We know that with our JAK inhibitors compared with dupilumab. Clearly, a lot of the inflammatory cascades help drive our signal for itch. As medical students, we learned about the itch-scratch cycle, which disrupts your skin. Altering that in and of itself helps perpetuate inflammatory cycles.

We definitely see that systemic treatments for our patients with atopic dermatitis using agents that address IL-4 and IL-13 help that inflammatory process and significantly reduce itch.

Joshua Zeichner, MD, and Vikash Oza, MD, discuss characteristics of type 2 inflammation and the impact of itching on pediatric patients with atopic dermatitis.

Characteristics of Type 2 Inflammation and the Impact of Itch

POLL: Which Most Recent FDA Approval Are You Excited About?

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Eric Simpson, MD, MCR, and professor of dermatology at Oregon Health & Science University presents exciting new systemic therapy treatment options for atopic dermatitis.

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Pigmentary disorders of the skin can be the cause of significant psychological distress in affected patients.

Articles

ICYMI, this week we had stories about product recalls, FDA warning letters, pediatric atopic dermatitis, acne treatment, and more. 

The Weekly Roundup: August 8-12

Almost 200 experts addressed uniform methotrexate (MTX) dosing for patients with psoriasis in an international consensus statement published in 

, following a survey study and conference.

Astrid van Huizen, MD, PhD, of the Department of Dermatology at Amsterdam University Medical Centers in the Netherlands, and colleagues, including the SPIN MTX Consensus Survey Study Group, conducted the research and facilitated the conference. The goal was to reach a consensus on uniform dosing guidelines for children and adults with psoriasis, including vulnerable patients.

When MTX was approved by the FDA for patients with psoriasis in the United States, there were no studies completed on the range of doses, the authors said.

 Even now there is no uniform dosing guid-ance. “A global survey study conducted by Psoriasis International Network (which is currently named the Skin Inflammation and Psoriasis International Network [SPIN]), showed that starting doses differed from 5 to 22.5 mg per week,” van Huizen et al reported.

With this survey study, researchers wanted to find an international consensus on MTX dosing for patients with psoriasis, and to discover and close knowledge gaps. Researchers said they examined 7 areas in the proposals: test dose; initiation dose; dose increase/decrease; form of administration; maximum dose; administration; and use of folic acid specified for adults, children, as well as vulnerable patients.

Following a systematic literature review that explored these topics, researchers created 21 pro-posals for MTX dosing and sent 3 rounds of modified electronic Delphi procedure study surveys to dermatology practitioners, dermatology residents, and psoriasis researchers between September 2020 and March 2021. Practitioners and residents had been recruited in June 2020 using SPIN and the European Academy of Dermatology and Venereology. “The participants worked mainly at a university hospital [97 (53.9%)] and were experienced in treating patients with psoriasis with methotrexate [163 (91.6%) had more than 10 years of experience],” researchers reported.

A total of 180 participants completed all 3 rounds of the surveys, which were created and distributed by Amsterdam University Medical Centers. A 9-point scale was used to evaluate proposals (1-3, disagree; 4-6, neither agree nor disagree; 7-9, agree). “Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree,” researchers said.

Van Huizen et al reported 11 proposals reached consensus in the first round of surveys, 3 did so in the second round, and 2 in the third round (16 total). Remaining proposals that did not reach consensus in the surveys were discussed at a June 2021 conference attended by 58 participants. Four more proposals reached consensus at the meeting, for a total of 20. Only 1 proposal did not reach consensus: “the proposal of an increased dosage of folic acid when increasing the dosage of MTX. During the consensus meet-ing, it was discussed that there was a lack of evidence and the available evidence was inconclusive,” researchers said.

®, van Huizen said the most significant takeaway from providers in practice was that no test dose of MTX is needed in adults, children, or vulnerable patients. “MTX can be started with 15 mg/wk in adults and 7.5 to 10 mg/wk in vulnerable patients. In children the MTX dosing should be based on square meter,” she said. 

She added that folic acid should be supplemented once a week, 24 hours after taking MTX. “In our study, no consensus is reached whether the dosage of folic acid should be increased, when increasing the dosage of MTX. Furthermore, the evidence for the use of folic acid is controversial and dosing regimens strongly depend on availability,” van Huizen noted. 

Van Huizen said that for next steps, the variability in treatment regimens might contribute to suboptimal treatment with MTX or can lead to early discontinuation of treatment due to limited efficacy or adverse effects. “With the publication of this consensus study we hope to raise awareness on the different used MTX dosages in daily practice and the need for a more uniform dosing regimen. Our published paper and presentations at international congresses on the 7th of July at the SPIN Congress in Paris can be included in reviews or implemented in guidelines and other supporting documents,” she told 

®. Van Huizen also said it is challenging to define a vulnerable population. “We discussed elderly patients or patients with an impaired kidney function in our study group. In future research, it should be defined for which subpopulation a specific dosing schedule is needed,” she said. 

For study limitations, van Huizen et al wrote that most respondents were from Europe, so investigators said surveying a more geographically diverse group of professionals may yield different results than respondents in non-Western countries. In addition, the authors said the study scope was limited because it did not include safety monitoring and screening of patients with psoriasis taking the drug. “We decided to focus on the dosing of MTX to prevent the survey being too extensive, because this could discourage participants from completing the survey rounds,” the authors said.

Van Huizen et al highlighted the study’s strengths: that participants were recruited from 7 continents and were academic professionals highly experienced in treating patients with MTX. They also noted the high 71.7% response rate (180 participants of 251 attempted recruitments). “Another strength is the design of this study; the anonymous eDelphi study avoided the possibility of dominance by any of the participants, but during the consensus meeting the proposals could also be discussed live,” researchers said.

The study authors emphasized that the current MTX guidelines should not apply to other inflammatory disorders or diseases such as alopecia areata, atopic dermatitis, and morphea. More high-quality studies should be completed to confirm these results, the study authors concluded. 

1. van Huizen AM, Menting SP, Gyulai R, et al. International eDelphi study to reach consensus on the methotrexate dosing regimen in patients with psoriasis. JAMA Dermatol. 2022;158(5):561-572. doi:10.1001/jamadermatol.2022.0434 

2. Gyulai R, Bagot M, Griffiths CEM, et al. Current practice of methotrexate use for psoriasis: results of a worldwide survey among dermatologists. J EurAcad Dermatol Venereol. 2015;29(2):224-231. doi:10.1111/jdv.12495

Results of methotrexate dosing for patients with psoriasis were published in the Journal of the American Medical Association Dermatology. 

International Experts Reach Consensus on Uniform Dosing of Methotrexate for Psoriasis

Ilya Petrou, MD, is a contributing writer for 

Whether caused by hyperpigmentation or hypopigmentation, pigmentary disorders such as melasma or vitiligo can be very challenging to treat and many patients often suffer from the negative psychosocial impact and significantly decreased quality of life associated with the many different forms of dyspigmentation of the skin. According to Seemal R. Desai, MD, a leading expert in skin of color and disorders of pigmentation, an acute knowledge of the diagnostic dilemmas, cutting-edge treatment options, and latest clinical research regarding the diagnosis and management of pigmentary disorders is par-amount and requisite to finding the optimal treatment and management plan in affected patients.

Skin color is influenced by the density or concentration of melanocytes; the number, size, and dispersion of melanosomes; and the nature of the pigment and its rate of degradation. Having a myriad of etiologies, the heterogenous group of pigmentary disorders includes hyperpigmented disorders such as melanosis or melasma, postinflammatory hyperpigmentation, drug-induced hyperpigmentation, solar lentigines, ephelides, café-au-lait macules, nevi, and melanoma and its precursors, as well as hypopigmented conditions, the most common of which include vitiligo followed by pityriasis alba, tinea versicolor, and postinflammatory hypopigmentation. 

“Whenever approaching patients with skin of color, it is important to understand that no single therapy exists to achieve the perfect balance of skin lightening and maintaining cutaneous integrity. This mantra is most relevant in the treatment of hyperpigmentation, including melasma, postinflammatory pigmentary alteration, drug-induced causes, or other etiologies. The bottom line is that it is important to keep an open mind regarding a multi-therapy approach, possibly involving office-based procedures and/or newer more literature-based treatment modalities,” said Seemal R. Desai, MD, FAAD, clinical assistant professor, Department of Dermatology, University of Texas Southwestern Medical Center, Dallas, Texas, who recently spoke at the Maui Derm NP+PA Summer 2022 conference.

Hyperpigmentation may be localized or diffuse in its presentation and is characterized by the darkening of an area of the skin caused by the overproduction of melanin, which can result from increased production of melanin pigment, or pigmentary incontinence, an accumulation of a large number of melanocytes, and deposition of other non-melanin pigments or substances in the skin. 

The most common hyperpigmentation disorder presenting in the dermatology practice is melasma, an acquired hypermelanosis of the skin seen predominantly in females with darker skin types and occurring most often on sun-exposed areas, mostly on the face and occasionally on the neck and forearms. With a still unclear pathogeny, melasma is an incurable condition that can be triggered by several factors, including sun exposure; genetic influences; pregnancy; sexual hormones; inflammatory processes in the skin; or use of cosmetics, steroids, or photosensitizing drugs. Many treatment options are available to clinicians, including topical retinoids, topical corticosteroids, azelaic acid, hydroquinone, chemical peels, cosmeceuticals, lasers, and dermabrasion, as well as a combination of these treatment modalities. Although melasma can be managed well with these treatment approaches, it can often recur or may never fully clear with current therapies. 

, the only FDA-approved combination branded formulation that can be used for melasma is Tri-Luma cream (Galderma Laboratories, LP), which has a concentration consisting of hydroquinone 4%, tretinoin 0.05%, and fluocinolone acetonide 0.01%. While hydro-quinone interrupts the formation and synthesis of melanin to help lighten the skin, tretinoin increases the skin cell turnover rate to help exfoliate the skin, and the corticosteroid helps reduce inflammation in the target area. 

“Typically, my personal workhorse compound therapy for melasma has been a hydroquinone-based triple combination lightening therapy consisting of hydroquinone ranging from 4% to 6%, tretinoin 0.025%, and dexamethasone 0.1%. Although used off label, in my experience this combination therapy has worked very well to help lighten the targeted skin in my melasma patients,” Desai said.

After taking standardized baseline photographic images, Desai will often use hydroquinone-based triple combination therapy for about 12 weeks in his melasma patients and, importantly, will always avoid prescribing unlimited refills for treatment. When patients follow up after the treatment course and appear to be doing better, Desai will switch them to a non–hydroquinone-based product to maintain the improvements achieved. 

Although there have been multiple studies on the safety of hydroquinone, Desai does not consider the medication to be carcinogenic because of the paucity of substantial evidence in randomized, double-blinded, placebo-controlled trials. Nevertheless, caution is advised as patients should not use the medication ad infinitum. According to Desai, hydroquinone has some limitations because it can cause exogenous ochronosis and can sometimes be irritating, necessitating its use in lower concentrations and for a limited amount of time. 

“Once some therapeutic success is achieved, we try to keep patients off hydroquinone for as long as we can and only go back to the medication when it is absolutely necessary. Hydroquinone is very effective in melasma; however, it should only be employed in the periods where you really need it,” Desai said.

Certainly, it can be challenging for patients to apply the medication correctly to gain the maximum benefit of treatment. As such, clinicians must consult and educate their patients appropriately in terms of precisely where and how to apply the medication effectively, including applying small amounts strictly on hyperpigmented lesions and in thin layers.

Regardless of the chosen treatment modality, Desai will very frequently advise his melasma patients to regularly use broad-spectrum sunscreens as well as topical antioxidants, such as vitamin C, throughout the treatment course. Other treatments that have shown good efficacy in melasma include chemical peels, such as azelaic acid in 15% to 20% concentrations applied twice a day and tranexamic acid com-pounded in a 3% concentration. In 1 study

, it was shown that tranexamic acid controls pigmentation by inhibiting the release of inflammatory mediators, specifically, prostaglandins and arachidonic acid, which are involved in melanogenesis, and the most effective dosing appears to be 500 mg daily, whether in topical, oral, or intra-dermal form. However, caution is advised for orally administered tranexamic acid as contraindications for the medication include current and past clotting episodes such as deep vein thrombosis and pulmonary embolism. Tranexamic acid is not FDA approved in any form for melasma or a skin indication.

On the opposite end of the spectrum, vitiligo represents the most frequently seen depigmentation disorder in the dermatology practice. Often dismissed as just a cosmetic issue, the common autoimmune depigmenting skin dis-ease typically presents as non-scaly, well-circumscribed, chalky-white macules and patches that can occur anywhere on the body, causing devastating psychological distress and social stigmatization, particularly in patients with darker Fitzpatrick skin types. It is the progressive destruction of the melanocytes in the skin that invariably results in the appearance of patchy depigmentation.

Whether presenting with unstable, chronic, or refractory disease, vitiligo remains very challenging to treat. Newer vitiligo subtypes have also recently been recognized, including confetti-like depigmentation (potentially indicating rapidly progressing vitiligo) and trichrome vitiligo (a variant of active vitiligo). The distinction between the variants is crucial as the currently available treatment and management options as well as prognosis differ according to variant type.

Depending on the variant, clinicians have a mosaic of treatment options at their disposal, including topical corticosteroids, vitamin D analogues, calcineurin inhibitors, depigmentation, systemic therapies, phototherapy, and surgical treatment. According to Desai however, recent research with Janus kinase (JAK) inhibitors, however, has brought much-needed hope to this patient population.

“This is a very exciting time for vitiligo patients because we now have the JAK inhibitors, which appear to be very effective in addressing the disease in preliminary trials, showing significant improvements in repigmentation. Ruxolitinib 1.5% cream (Opzelura; Incyte), in particular, has shown to be very effective in improving symptoms, and the medication is now FDA approved. This is a very exciting therapy that can now be added to our armamentarium for our vitiligo patients,” Desai said.

Even though ruxolitinib is applied topically, treatment with the novel JAK inhibitor is still not without risk and patients need to be well informed of the potential adverse events. Vitiligo patients are nevertheless very open to the new medication, Desai said, as other tried-and-failed therapies leave them with a sense of hopelessness, making them eager to try a new medication that appears to be relatively safe while showing good efficacy in trials so far.

Antioxidants, oral therapies, laser and light therapies, and the topical JAK inhibitors can be used in combination and, according to Desai, many patients are very excited to try out new treatments and combination therapies simply because of the significant frustration and psy-chological burden associated with their disease.

“Many patients see their physician and can get easily frustrated after failing any number of therapies. Nevertheless, they need to be educated and well informed that there are evolving treatments that are proving to be effective, and it is the clinical path that patients and their physicians must travel together in search of the right treatment plan that works for their individual case,” Desai said. 

Unfortunately, relapses are not uncommon and Desai said tacrolimus 0.1% cream can help stabilize the disease. According to Desai, many times one can reduce the risk of relapse to about 10% of repigmentation by applying tacrolimus ointment twice weekly as a pulse monotherapy, as was recently shown in a study by Cavalié et al.

“Relapses are not a doomed failure of treatment, but instead should be simply viewed as a setback, a common occurrence in inflammatory diseases such as vitiligo. Should a relapse occur, the key is not to panic because they can be managed, as we have many different treatment options to quell symptoms. The ‘right’ therapeutic regimen just needs to be found for the individual patient,” Desai said. 

1. Tse TW, Hui E. Tranexamic acid: an important adjuvant in the treatment of melasma. J Cosmet Dermatol. 2013;12(1):57- 66.doi:10.1111/ jocd.12026

2. Cavalié M, Ezzedine K, Fontas E, et al. Maintenance therapy of adult vitiligo with 0.1% tacrolimus ointment: a randomized, double blind, placebo-controlled study. J Invest Dermatol. 2015;135(4):970-974. doi:10.1038/jid.2014.527 

3. Desai S. Disorders of pigmentation. Presented at: Maui Derm NP+PA Summer 2022; June 23-25, 2022, Colorado Springs, Colorado.

Desai is a consultant for Galderma Laboratories, Almirall, Ferndale Laboratories, Gore Range Capital, Bristol Myers Squibb, AbbVie, Verrica Pharmaceuticals, UCB, and Ortho; is a speaker for Pfizer; is a board member or executive for the Foundation for Research and Education of Dermatology, Dermavant Sciences, and the Women’s Dermatologic Society; does contracted research for AbbVie, Incyte Corporation, Dermavant Sciences, and AOBiome; has ownership interest in Gore Range Capital; and has another financial relationship with the National Psoriasis Foundation.

Pigmentary disorders of the skin can be the cause of significant psychological distress in affected patients. 

Diagnostic Approaches for Melasma and Vitiligo

Joshua Zeichner, MD, an associate professor of dermatology and director of cosmetic and clinical research in the Department of Dermatology at Mount Sinai Hospital in New York, New York; and Mona Gohara, MD, a dermatologist at Dermatology Physicians of Connecticut in Hamden, Connecticut, and president of the Women’s Dermatologic Society, discussed their experiences and preferences in treating acne with non-prescription drugs. 

To determine the efficacy of over the counter (OTC) acne drugs, Zeichner and Gohara first discussed a 2019 study

 that analyzed adherence issues of topical treatments for acne vulgaris. Patients from the study used retinoids, antibacterial treatments, benzoyl peroxide, retinoid antibacterial treatments, and formulas containing resorcinol salicylic acid. Nearly half of the patients discontinued topical therapy before their scheduled time, citing unresponsiveness and adverse effects as primary reasons. Gohara began the discussion by saying she is not surprised by the number of patients who discontinue topical therapies, noting that many of her patients have told her their topical therapies did not work. 

Gohara stressed that retinoids and benzoyl peroxide are the gold standards for acne treatment in dermatology, but only when used correctly. While these OTC drugs are not prescription strength, they can still be irritating to the skin when used in large quantities or mixed with other irritating agents. Gohara explained that she gives her patients a handout that shows how to use OTC drugs, such as retinoids, correctly. She said dermatologists should take time to talk with their patients about how to use the product, as well as realistic expectations. 

Zeichner echoed these experiences, saying he gives his patients specific guidance on how much product to use, how often, and what other OTC products to combine with topical therapies for the best results. He noted that a pea-sized amount of product is typically all you need; a cherry tomato-sized amount is too much. Overall, Zeichner sees that many patients want results too quickly; most patients will not see results until approximately week 12. Another way Zeichner tries to understand his patients’ expectations is by asking them to walk him through their skin care regimen. This helps Zeichner know what they already use and what kind of results they desire. 

“I always say to patients when they come back, ‘First of all, how do you feel about your skin?’ I like to hear what they have to say before I make a comment and I’ll say to them, ‘Take me through your regimen.’ I always ask open-ended questions. We have to be nonjudgmental, educate our patients, and set realistic expectations,” said Zeichner. 

Most importantly, both experts stressed that it’s crucial not to be judgmental. Asking patients questions will benefit both the dermatologist and the patient to come up with an agreed-upon acne treatment plan. Gohara also mentioned a few tricks, such as mixing a light moisturizing cream with a retinoid or benzoyl peroxide to cut the irritation and not using retinoids as a spot treatment. 

Zeichner and Gohara discussed non-prescription cleansers and moisturizers for acne-prone skin. In a 2020 study

, 4 name-brand, lipid-free cleansers were studied and compared. Gohara began by pointing out the beneficial ingredients of each product. She stressed that hydrating ingredients are always beneficial, no matter the type of skin. Both Zeichner and Gohara mentioned the importance of a healthy skin barrier. A strong skin barrier is not always the first thought in acne management, but it’s the skin’s line of defense. Ceramides in cleansers help the outermost layer of skin by keeping irritants out and keeping water locked in. Skin barrier dysfunction is related to blockages in the pores that contribute to acne. 

“Lipid-free cleansers are primarily composed of water and glycerin; those are the 2 primary ingredients, which are obviously very highly rated,” said Gohara. “We can see that primarily, these cleansers will have very low rates of irritation on the skin and can help the skin barrier, which is what we were talking about before. Lipid-free cleansers can mitigate the irritation that patients may be getting from retinoids and benzoyl peroxides.” 

The main goal of moisturizers is to repair significant defects in the skin barrier and assist with acne treatment. Gohara said dermatologists and patients must be deliberate when selecting a moisturizer. She considers structural components of the skin and whether the moisturizer is depositing ceramides into the epidermal barrier. Additionally, moisturizers can have other ingredients such as sunscreen that are also beneficial to the skin. 

Both Zeichner and Gohara noted 3 top ingredients for hydrating skin in moisturizers:

•occlusives: create a blanket to prevent transepidermal water loss (TEWL)

•humectants: suck water up from the dermis and epidermis

•emollient: a layer between epidermal cells to stop TEWL 

Moisturizers should have more ingredients than just a humectant, as humectants are great at grabbing water, not trapping it. Hyaluronic acid is an example of one that should not be used alone and should be layered with a moisturizer. 

To end another informative webinar series, Zeichner and Gohara concluded that OTC skin care products such as cleansers and moisturizers should never compromise the integrity of the skin barrier. Products should include ingredients that will protect, soften, and hydrate the skin, not irritate it. Discussing OTC products and individualized treatment plans with acne-prone patients will result in better adherence rates as well as achievable expectations. 

Zeichner J, Gohara M. The role of non-prescription products in the management of acne. Between the Lines webinar. July 15, 2022. Accessed July 20, 2022.

In a webinar from the Between the Lines series, 2 dermatology experts discussed challenges in adherence with acne treatments, updates on available moisturizers and cleansers, factors that influence the selection of moisturizers and cleansers for acne-prone patients, and data from 2 studies.  

 For our last question, I want to focus on therapy. Let’s review the options we have for mild to moderate atopic dermatitis [AD], in terms of topicals and systemic medications. Vikash, lead this off for us. Take us through the topical options in terms of emollients or moisturizers and prescription options.

 In terms of prescription options, our true standby is still topical steroids. Although we have all these newer therapies, topical steroids are still effective for addressing acute flares. Many times, they can be cheaper in our health care system, and they play a large role in getting through a flare. A lot of times, patients struggle with the maintenance of the chronic aspect of their disease, especially the patients who come to see us. Most patients who see a specialist often have moderate to severe disease and need a maintenance therapy. That’s where we’re leaning toward potentially nonsteroid options.

Depending on your age, you have different FDA-approved options. For infants aged 3 months and older, we have crisaborole, or Eucrisa. For children aged 2 years and older, we have tacrolimus 0.03% and pimecrolimus. For patients aged 16 and older, we have tacrolimus 0.1%. Our newest agent for patients aged 12 and older is topical ruxolitinib. We’re starting to incorporate these therapies as maintenance of disease, getting someone through a flare but having a therapy that we feel you can use on an intermittent basis to maintain your disease control if you don’t fall into that threshold of having a systemic disease.

As Raj brought up at the start, the second pillar is skin care. It’s interesting that we have these directed therapies. With our skin care, we still don’t have directed therapies for their specific barrier problem because there’s probably a lot of variability. But a lot of what we have over the market are ceramide-enriched emollients, which are important as the mainstay. We have literature showing that appropriate use of an emollient 2 to 3 times a day can potentially reduce the frequency of flares. They’re important.

From a clinician standpoint, 1 thing I’ve de-emphasized a little over time in my first visit with a patient with atopic dermatitis, when we’re trying to get them under control and out of a flare, is to focus on prescription therapies in those first several weeks because they’ve already exhausted everything that their pharmacy has to offer from emollients. Gentle skin care is clearly important, but getting them to the point where they’re over this hump of inflammation, where maintaining their skin barrier can help as a preventive way of reducing flares, is conceptually a construct that I help guide them through.

 Brit, let’s have you close this out for us. Take us through some of the traditional systemic medications and newer biologics that we have for atopic dermatitis.

 Fortunately, this conversation has changed a lot, even in the past several years. Before targeted therapy, we were using a lot more chronic topicals and having patients who are teetering have their parents or themselves do a lot of work at home just to keep them OK, including wet wraps and all these things; it’s like a full-time job. There are data that caregivers spend about 22 hours a week with their child with atopic dermatitis. We accepted that before because our options were these things that had a decent amount of risk associated with them. It was more traditional immunosuppressants, like cyclosporine, mycophenolate, and methotrexate. We would pull the trigger on those. But at least for me, I waited until I felt like it was so bad that I could justify the risk and put the patient through blood draws and have a conversation about risk for malignancy and infection, etc.

Having more targeted therapies has made me realize that I was tolerating a level of disease that I probably shouldn’t have been because the options weren’t that great. We have those more broadly acting traditional immunosuppressants. There are oral corticosteroids. That almost never happens in my clinic unless I’m bridging somebody to something else, because we know those are a Band-Aid. They’re a short-term solution. Unfortunately, a lot of patients are still given chronic oral steroids—they’re going to see someone who’s giving them intramuscular triamcinolone every few months, and we can’t underestimate the risk of that long term. I’ve seen patients with osteopenia from chronic oral steroids for their atopic dermatitis. We need to move beyond that. We don’t have to do that now at all.

With dupilumab, it was a major breakthrough to have a targeted therapy without talking about a black-box warning or doing blood draws. Now we have approval down to the age of 6 months. If anything speaks to safety, even in our adult patients, it’s that. Having dupilumab in my toolbox has enabled me to pull the trigger earlier on patients and impact their quality of life in a huge way. Earlier, there was the point made about how people don’t even how bad it is. That’s because they’ve always been like this. With psoriasis, people come in and say, “What is this? Make it go away,” or someone has 5% body surface area and you say, “You need a biologic.” That’s because they had normal skin and then they got psoriasis and they want to go back to who they were before. But with AD, they don’t know any different. We have to help people understand it. “Now there is something. I know things haven’t worked for you in the past, or there were scary adverse effects. But now we have options.”

Following dupilumab, we have tralokinumab inhibiting IL-13, and we’ve recently had 2 oral JAK inhibitors approved, with upadacitinib for patients aged 12 and up and abrocitinib for patients aged 18 and up. Those therapies can be very effective and work quickly on itch, but in my mind and by their labels, they’re in the second line after a biologic like dupilumab. That’s more of a conversation because they’re acting intracellularly and more cytokines are floating through there. There’s more discussion about adverse effects and risk. But it’s amazing for patients, because although many people will do well with dupilumab, there are going to be some people for whom it isn’t completely effective. For them we now have an option if they’re aged 12 or older. But we’re going to see trials in younger populations too.

This is a disease that people aren’t going to have to live with. It has taken a while, but we’re going to be where we are with psoriasis very soon. What’s cool is we’ve started with a super-targeted, great safety profile compared with what we’ve had to do with biologics in psoriasis.

 As we look at the total population of patients, in many ways, it’s an easy decision on how to treat mild patients and severe patients. Even before we had the more targeted therapies, it was worth the risk to get a benefit for severe patients. But the people who had the most unmet need were the moderate patients. These were people to whom I’d personally give a tub of triamcinolone. It was doing OK, but they weren’t quite bad enough in my mind to justify a systemic immunosuppressant medication, such as cyclosporine. But now we have targeted biologics that address IL-4 and IL-13 and have such a great safety profile—there’s a systemic agent that can change the lives of these moderate patients in whom previously I wouldn’t even have considered a systemic medication. In my practice, it’s a home run across the board, especially for those moderate patients.

 Some of those patients are the most grateful, such as the person who isn’t erythrodermic but is just never clear. They can’t go on vacation without their triamcinolone. Everything is greasy. They get a new life afterward. We’re talking about therapies that have a great adverse effect profile. We shouldn’t be waiting on those people. If they come in and are on 3 different prescriptions, and they’re having to use 1 on this day and another on another day and they can’t keep track, and they’re waking up scratching, then we need to move on and treat them more appropriately.

 For everybody listening to this, my message is to remember that the full indication for these systemic biologics is moderate to severe. Don’t forget about those moderates, where we can make a huge impact on quality of life.