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

In contrast to previous research, a study conducted at one of the largest children’s hospitals in China showed that only a small percentage of children with vitiligo had abnormal thyroid function.

showed that eight of 219, or 3.7%, children with vitiligo whose thyroid function was tested had abnormal results. Ting Dai, M.D., Ph.D., and colleagues noted that a 

 conducted in eastern China showed almost 44% of children diagnosed with vitiligo had thyroid dysfunction. But they also referenced a Korean study with results that were closer to theirs: 5.9% of the children with vitiligo in that study had test results indicating abnormal thyroid function and that there wasn’t a difference between the children with vitiligo and a comparison.

The researchers said that possible explanation for the difference between their results and the previous study in eastern China is that the children in their study were younger and that thyroid abnormalities develop later. Dai and colleagues also mentioned issues with study design and selection bias.

This study was conducted at the Children’s Hospital of Fudan University, which the authors said is the largest in eastern China. It was a retrospective study that included a total of 244 children seen at the hospital’s vitiligo clinic between September 2019 and April 2021.

There are many theories about what causes vitiligo, ranging from genetic (25% to 50% of people with vitiligo have an affected relative) to autoimmunity to neuronal (neural endings secreting a neurochemical mediator that is toxic to melanocytes). This study was yet another attempt to shed some light on the subject. To further complicate matters, as Dai and colleagues mention, some research that childhood vitiligo might be a distinct clinical entity.

In this study, all the patients were younger than 18 and the average age of onset was 5.3 years. which the researchers said is younger than the age of onset of previous studies.

The Fudan University researchers also looked at atopy (allergies) and autoimmune disease. About 1 in 3 children in the study (73 out of 244) had at least one atopic disorder, including atopic dermatitis (31 of 244, or 12.7%) and atopic rhinitis (50 of 244, or 20.5%).

Roughly the same proportion of the children in the study (52 of the 157 who were tested) had elevated levels of immunoglobulin E (IgE), the antibodies that are overproduced in people with allergies that lead to allergy symptoms.

Twenty (8.2%) of the 244 children in the study had been diagnosed as having an autoimmune disorder, a group that included eight children with thyroid disorder and four with alopecia areata. The researchers also found an inverse relationship between autoimmunity and IgE levels.

These findings were published in the September 2022 issue of the 

 They were posted earlier online in March 2022.

This article was originally published by Managed Healthcare Executive. 

Articles

The search for the causes of vitiligo continues. The findings in this study stand in contrast to another one conducted in eastern China that showed a high percentage of children with vitiligo had thyroid abnormalities.

Thyroid Abnormalities Rare Among Children with Vitiligo, Study Finds

Ilya Petrou, MD, is a contributing writer for 

When it comes to diagnosing unusual dermatologic diseases, a careful history from the patient and a close eye for diagnostic work-up detail can help shorten the road from A to B and get patients on the appropriate treatment and management path.

This article offers strategies to help prevent misdiagnosis of 2 rare skin diseases: Merkel cell carcinoma and actinic prurigo.

Merkel cell carcinoma (MCC) is a rare, aggressive form of skin cancer. Approximately 3000 new cases of MCC are diagnosed annually in the United States. Tumors from MCC usually occur in sun-exposed areas, are common on the head and neck of older White men, and carry a high risk of recurrence and metastasis. The main risk factors for MCC include UV exposure, advanced age, and immunosuppression, and the development of MCC is associated with the Merkel cell polyomavirus.

Although the lesion itself can appear suspicious to the astute clinician, many dermatologists may miss the diagnosis upon first examination, according to Paul Nghiem, MD, PhD, professor and head of the Division of Dermatology and the George F. Odland Endowed Chair in Dermatology at the University of Washington in Seattle.

“Statistics show that even dermatologists get the clinical diagnosis of MCC wrong the majority of the time,” Nghiem said. “The main challenge is to decide that a biopsy needs to happen. Most dermatologists who biopsy an MCC will be surprised by the pathology report because MCC does not have a specific appearance and it is uncommon.”

In a systematic cohort study of 195 patients diagnosed with MCC between 1980 and 2007,

 Nghiem and colleagues aimed to define the clinical characteristics of MCC to identify features that may help clinicians better recognize the aggressive skin cancer. Their findings showed that 88% of MCCs were asymptomatic (nontender)—despite rapid growth in the prior 3 months (63% of lesions) and being red or pink (56%). In addition, 56% of lesions were presumed to be benign, with a cyst or acneiform lesion being the most common diagnosis given (32%), followed by lipoma (6%) and dermatofibroma (5%).

The investigators summarized the most significant clinical characteristics of MCC in an AEIOU acronym:

According to Nghiem, almost all patients with MCCs will have 3 or 4 clinical features in AEIOU. He noted, however, to be cautious because these characteristics are not MCC specific and may apply to other lesions. A biopsy will be telling.

“If you’ve got an older patient who is immunosuppressed and has a history of nonmelanoma skin cancer...and sun-damaged skin and presents with a suspicious quickly growing nodule on the skin, a biopsy should be performed and will likely be definitive,” Nghiem said.

Performing a biopsy early on is advantageous because, according to Nghiem, the cancer will have already spread beyond the primary site in more than one-third of cases. Therefore, it is paramount to treat MCC appropriately soon after the diagnosis is made.

The management of MCC is more complicated than any other skin cancer, but fortunately, there is increasing agreement in many aspects of how MCC should be managed. Nghiem noted that MCC management should follow a multidisciplinary approach. Surgery is often, but not always, the first step in treatment. Unlike melanoma, a full work-up for staging (full body scan and usually a sentinel lymph node biopsy) is indicated in almost all cases before deciding on therapy because the tumor will have spread beyond the primary site in almost half of cases.

“Clinicians should be wary and have a lower threshold to perform a biopsy in patients with prior skin cancers and a nontender lesion arising on sun-exposed skin, especially if the immune system is compromised,” Nghiem said. “Even if you’re not thinking about MCC upon first examination, such features should be of concern and make the clinician lean toward biopsy.”

Also having UV exposure in its pathogenesis, actinic prurigo is another rare dermatologic disease that is challenging to treat and manage. A rare form of idiopathic photodermatosis, actinic prurigo primarily affects sun-exposed areas, including the face, neck, dorsal surface of the upper extremities, lips, and conjunctival mucosa. The disease follows a chronic course, with patients typically presenting with indurated, intensely pruritic erythematous papules, nodules, and excoriated plaques on sun-exposed areas of the skin.

“When a patient presents with an intensely pruritic skin eruption that’s restricted to sun-exposed areas, dermatologists need to think of all the differential diagnoses related to photosensitive sun-induced reactions,” said Bernard A. Cohen, MD, a professor of dermatology and pediatrics at Johns Hopkins University School of Medicine in Baltimore, Maryland. “Given the fact that actinic prurigo is persistent, sometimes lasting for months, can recur, or [that] the patient [may continue] to get sun exposure, it can be a horribly itchy, life-compromising reaction.”

Current histological and research findings suggest that actinic prurigo is an ongoing type 4 hypersensitivity reaction with still unknown other immunopathogenic processes, including the involvement of the 

 gene; the infiltration of CD4 lymphocytes, eosinophils, and mast cells; and a serum increase in IgE. Lesions appear hours or days after sun exposure (long- and short-wave UV-A and UV-B), which is contrary to the course of solar urticaria, in which skin lesions appear only minutes after UV exposure.

“Actinic prurigo may look a little urticarial at first, but it is persistent and will not disappear easily within 24 hours like urticaria would,” Cohen said. “Solar urticaria is something that lasts just minutes to hours, certainly less than 24 hours by definition, whereas actinic prurigo will be persistent and continue to spread and may eventually even involve areas that are not sun-exposed, such as the buttocks.”

The main differential diagnosis of actinic prurigo is polymorphous light eruption, followed by atopic dermatitis with photosensitivity and solar urticaria. Although actinic prurigo can affect people of all ages, approximately one-third of patients are children, with boys and girls being equally affected. In adult-onset actinic prurigo, however, women are affected 2 times more often than men.

Because many patients first develop symptoms during childhood, Cohen said the main clinical consideration to rule out in this younger population is atopic dermatitis with photosensitivity. In adults, photoallergic contact dermatitis and chronic actinic dermatitis are other dermatologic conditions that need ruled out in patients presenting with photosensitivity of a chronic nature.

Meticulous history taking is requisite during the consultation and can help clinicians rule out other potential differential diagnoses. Contrary to polymorphous light eruption and other dermatoses in which UV and photosensitivity play a central role in disease pathogenesis, actinic prurigo will be different particularly in its long-term persistence and can progress even though patients protect themselves from sunlight. Nevertheless, disease management for actinic prurigo begins with sun protection and sunlight avoidance.

Early diagnosis and proper management are key to help limit patient morbidity. Current treatments include topical antihistamines, corticosteroids, emollients, and photochemotherapy, as well as systemic therapies for severe cases.

“Topical corticosteroids are the first-line therapy, and to optimize treatment outcomes, it is crucial to apply them in the beginning when lesions first appear,” Cohen said. “The earlier you recognize the symptoms, the earlier you can start an aggressive topical therapy, [and] the better the chances of effectively treating actinic prurigo.”

1. Heath M, Jaimes N, Lemos B, et al. Clinical characteristics of Merkel cell carcinoma at diagnosis in 195 patients: the AEIOU features.

 2008;58(3):375-381. doi:10.1016/j.jaad.2007.11.020

Thorough history taking is essential during the consultation and can help clinicians rule out other potential differential diagnoses. 

Preventing Misdiagnosis of Rare Skin Diseases

New results from a nonrandomized clinical trial show apremilast (Otezla; Amgen Inc.)may provide patients with cardiometabolic disease and psoriasis an added benefit. In a study published in 

, scientists say they discovered the drug may also help patients with psoriasis reduce overall body fat.

 Visceral fat is stored within the abdominal cavity, and located near several vital organs, including the liver, stomach, and intestines. It can cause several dangerous health conditions, such as diabetes, hypertension, stroke, and cancer.

Researchers at the Perelman School of Medicine at the University of Pennsylvania measured changes in 70 study participants with moderate to severe psoriasis. Sixty patients completed week 16, and 39 completed 52 of the single-arm, open-label trial conducted between April 2017 and April 2021. The participants all took 30 mg of apremilast, an oral phosphodiesterase-4 (PDE-4) inhibitor approved for treating psoriasis and psoriatic arthritis, twice daily.

The study found no change in aortic vascular inflammation at week 16 (target to background ratio, −0.02; 95% CI, −0.08 to 0.05; 

 = .61) or week 52 (target to background ratio, −0.07; 95% CI, −0.15 to 0.01; 

 = .09) compared with baseline. The authors wrote that at week 16, there were reductions in levels of interleukin-1b, fetuin A, valine, leucine, and isoleucine. At week 52, the authors noted reductions in ferritin levels, cholesterol efflux capacity, ß-hydroxybutyrate 16, acetone, and ketone bodies, and an increase in levels of apolipoprotein A-1.

Apremilast was approved by the US Food and Drug Administration in 2014 to treat plaque psoriasis. It has been prescribed to more than 250,000 patients with moderate-to-severe plaque psoriasis or active psoriatic arthritis in the country. Approximately 9 million people in the US suffer from plaque psoriasis, including adolescents and adults.

 Plaque psoriasis affects different parts of the body, including areas like the face, elbows, knees, genitalia, and other areas of skin-to-skin contact.

Study researchers say larger controlled studies are needed to better determine if apremilast is effective at helping psoriasis patients lose weight, because of the small population studied. In the meantime, they urge doctors to screen for cardiovascular disease in psoriasis patients.

1. Gelfand JM, Shin DB, Armstrong AW, et al. Association of Apremilast With Vascular Inflammation and Cardiometabolic Function in Patients With Psoriasis: The VIP-A Phase 4, Open-label, Nonrandomized Clinical Trial. 

 Published online September 21, 2022. doi:10.1001/jamadermatol.2022.3862

2. Penn Research Finds Psoriasis Medication Apremilast Leads to Fat Loss in People with Psoriasis.Pennmedicine.org. Accessed September 28, 2022. 

https://www.pennmedicine.org/news/news-releases/2022/september/medication-apremilast-leads-to-fat-loss-in-people-with-psoriasis

3. Gao JC, Wu AG, Contento MN, Maher JM, Cline A. Apremilast in the Treatment of Plaque Psoriasis: Differential Use in Psoriasis. Clin Cosmet Investig Dermatol. 2022; 15:395-402. Published 2022 Mar 8. doi:10.2147/CCID.S266036

New research finds psoriasis drug apremilast could help patients lose weight.

Study Reveals Psoriasis Drug May Have Cardiometabolic Benefits in Patients with Psoriatic Disease

The US Food and Drug Administration has approved dupliumab (Dupixent; Sanofi and Regeron Phamaceuticals, Inc.) for the treatment of prurigo nodularis in adult patients. Recently, Dermatology Times© spoke with Amy Spizuoco, DO, FAOCD, a dual board-certified dermatologist and owner of True Dermatology in New York, New York to discuss how she believes dupliumab will change the way dermatologists treat prurigo nodularis. 

: This is huge for us in the dermatology community, because patients who have prurigo nodularis suffer from extreme itching and skin lesions andup until now, we've not had anything that's super successful and effective, or FDA approved for the treatment of these conditions. Having dupilumab approved for patients with prurigo nodularis is going to change how I treat patients, because now I have something that is FDA approved and has proven efficacy and safety and tolerability for my patients, as opposed to just kind of, you know, throwing the kitchen sink at them, you know, topical steroids, light treatments, you know, things that aren't super effective and not FDA approved.

: Do you see a lot of patients that are just very frustrated with this condition?

Yes. All over our dermatology community and even in primary care and other specialties. We see tons of patients suffering from this condition, because it's extremely itchy and a lot of them affect their activities of daily living. They can't sleep, they're not concentrating at work, they are not concentrating in school. We see tons of patients suffering with this condition that haven't had good treatment that's effective and safe for them.

: Understood! Is there anything else you want to add?

: Just that I'm really excited that this medication is now going to be approved for our patients suffering with prurigo nodularis. We've seen its efficacy in patients with atopic dermatitis and other conditions in the allergy immunology world. So, it is nice to see that we have something that is approved and is effective for our patients suffering from extreme itch and skin lesions.

1. Study of Dupilumab for the Treatment of Patients with Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (PRIME2). ClinicalTrials.gov identifier: NCT04202679. Updated September 28, 2022. Accessed September 28, 2022.

https://clinicaltrials.gov/ct2/show/NCT04202679?term=PRIME2&cond=Prurigo+Nodularis&draw=2&rank=

2. Study of Dupilumab for the Treatment of Patients with Prurigo Nodularis, Inadequately Controlled on Topical Prescription Therapies or When Those Therapies Are Not Advisable (LIBERTY-PN PRIME). ClinicalTrials.gov identifier: NCT04183335. Updated February 17, 2022. Accessed September 28, 2022.

https://clinicaltrials.gov/ct2/show/NCT04183335?term=PRIME%2C+dupilumab&draw=2&rank=1

Videos

Sanofi and Regeneron’s dupliumab will provide relief to patients with extreme itch and skin lesions. 

FDA Approves Dupliumab for Prurigo Nodularis  

I agree completely that the diagnostic delay leads to more joint damage. In the long run, it’s harder to control psoriatic arthritis [PsA]. That’s recently been shown even for psoriasis with some of the newer agents that we have. For psoriatic arthritis, it was shown years ago that the later you start therapy, the harder it is to control. How do you think we can overcome that? Is there anything we can do to ensure a timely diagnosis?

Yes, regular screening. We’re asked how frequently we should be screening. It’s a quick and easy thing to do. I recommend screening at every visit, at least every 6 months in these patients. Whenever we see a patient with psoriasis, regular screening makes sense, increasing awareness as we’re doing among physicians but also among patients. Patients should be aware, and many organizations are doing that. We can do that as well. We counsel our patients with psoriasis that they’re at risk, so they should let us know if they’re experiencing new-onset musculoskeletal symptoms, joint symptoms, etc.

Years ago, we published a PsA mnemonic. It’s not a formalized screening tool, but I love to teach my colleagues about this because it’s easier to remember PsA. Ask about P, pain. You want to qualify that with stiffness. Do they have prolonged stiffness that lasts more than 20 or 30 min? That might suggest inflammatory arthritis. There are a couple of other Ss in there. One S is for sausage—dactylitis that Mark mentioned. That’s specific to psoriatic arthritis. Another is swelling. Those are going to make you think more about inflammatory arthritis. A is for axial disease. Ask if they have inflammatory type back pain. Do they have back pain that improves with activity? That’s something that’s occurring more, maybe in a younger patient where you might expect less likely to be seeing inflammatory back pain. PsA is easy to remember.

We do have more formal screening tools. For example, we have the pest screening tool. It’s a simple 5-question tool that’s very easy on the dermatologist and on the office because it’s patient-facing. It’s something a patient can complete in the waiting room. While they’re waiting to see you, it could be pushed to them through a gateway if you have an electronic patient gateway for them to complete. If it’s positive, you can decide how much of it you want to own. It could facilitate a discussion about psoriatic arthritis, or it could be simply, “You’ve screened positive, and I’m going to refer you to 1 of my rheumatology colleagues to take a deeper dive.” It’s very easy, it’s a low burden on the office. Increasingly, my colleagues are aware of this. It’s really about the question, “Once the patient screens positive, what do I do with it?” We can talk about this more, but we dermatologists can increasingly get comfortable with the diagnosis.

Mark made a beautiful comment a few moments ago that sometimes he does a diagnostic therapeutic maneuver. If my suspicions are high enough, if I’m choosing an agent that I know can treat psoriatic arthritis, I’m going to treat them. I’m going to have that conversation with the patient if my suspicions are high that they have PsA. When they come back, we’re going to say, “How do you feel? How have your symptoms changed?” That’s 1 approach. Another is to refer to the rheumatologist if you think they can get there a timely manner. We have a lot of interest in this. Years ago, we developed a group called PPACMAN [Psoriasis & Psoriatic Arthritis Clinics Multicenter Advancement Network], which looks at setting up facilitated referral networks or minimally setting up facilitated communication between dermatologists and rheumatologists so we can phone a friend, send an email, get a patient in sooner, or have an offline chat about the right thing for this patient in front of us. All of that is to avoid the delays in treatment and become, over time, more confident in diagnosis and treatment that gets the patient to the right therapy.

Mark, I’d like to hear your reflections on that. I unpacked a lot, but screening is key. What do you think, from a dermatologist’s perspective, about dermatologists getting more confident and comfortable with diagnosis and treatment? We’re talking about a variety of MOAs [mechanisms of action], of treatment, facing psoriasis and psoriatic arthritis. Why not choose 1 of those at a juncture when you think your patient has PsA and see what happens? How do you train your residents and our colleagues about that?

Of the treatments we use for psoriatic arthritis, it turns out they work really well for psoriasis too. If there’s even a suspicion it’s worth using 1 of the treatments we mentioned already: TNF [tumor necrosis factor] alpha-blockers, IL-17 blockers, and JAK inhibitors. The JAK inhibitors are not approved for psoriasis, but they work quite well. Any would be useful if you think the patient has psoriatic arthritis. The JAK inhibitors have some boxed warnings, so it’s suggested that they might follow other treatments. They won’t necessarily be the first treatment you use, but they’re quite effective.

One thing we all agree on is that you should ask a patient when you see them, “How are your joints? Do they hurt? Are they stiff?” That’s an easy question. It takes almost no time and dermatologists are pressed for time. We’re being asked to see more patients in less time, but that’s an easy question. It has a profound impact on the treatment of your patient. It’s worth asking that question at every visit because I said already 70% of the time, psoriasis proceeds to arthritis. So, when you end up with the diagnosis of psoriatic arthritis, most of the time it’s going to occur after you first see that patient. It’s worth asking that question at every visit, assuming the visits are 6 months apart or something like that.

On the flip side, some of my colleagues get nervous about referring patients. I say, “I did the rheumatology half of my training for a reason. That’s what we’re there for.” If a patient is uncomfortable, they have musculoskeletal pain. It’s unclear. That’s why we want to see them, so please refer them. We can take a deep dive, and there’s nuance if we need to get plain films and sacroiliac joint x-rays for axial disease and other advanced imaging. We’re happy to do it, so send them. That’s always a good take-home point.

Mark G. Lebwohl, MD, and Joseph F. Merola, MD, MMSc, provide tips to overcome diagnostic delay in psoriasis.

Overcoming Diagnostic Delay in Psoriasis

POLL: How Many People in the US Have Generalized Pustular Psoriasis?

This week's edition of the Mainstream Patient features stories about the best sunscreens for fall, Botox for excessive sweating, Brad Pitt's entrance into the skin care industry, and more.

New Study Data of Roflumilast Foam for Scalp and Body Psoriasis

Arcutis Biotherapeutics announced positive results from the ARRECTOR phase 3 trial.

Ruxolitinib Cream Rapidly Reduced Itch for Atopic Dermatitis in Phase 3 Study

Recent study results demonstrated a noticeable reduction in itch just 12 hours after application of ruxolitinib.

A recent review article lists six other JAK inhibitors that might be used as treatments for vitiligo in addition to ruxolitinib, the active ingredient in recently approved Opzelura.

Feds Warn of Monkeypox-Themed Malicious Email Campaign Targeting Health Care Providers

Don’t click on links or attachments unless you’re sure they are legitimate.

FDA Clears CellFX System for the Treatment of Sebaceous Hyperplasia

Pulse Biosciences' new technology will treat sebaceous hyperplasia patients with Fitzpatrick skin types I-III.

Pointers With Dr Portela: Skin Conditions with PCOS

In this week’s Pointers with Dr Portela, the 208SkinDoc discusses common skin conditions related to polycystic ovary syndrome.

Expert dermatologists discuss challenges in diagnosing a patient with PsA.

FDA Approves Dupliumab for Prurigo Nodularis

Sanofi and Regeneron’s dupliumab will provide relief to patients with extreme itch and skin lesions.

Thorough history taking is essential during the consultation and can help clinicians rule out other potential differential diagnoses.

Expert dermatologists discuss future directions for the management of basal cell carcinoma.

Patient Case: 49-Year-Old Caucasian Woman With Neglected Large BCC

Sherrif F. Ibrahim, MD, PhD, presents the case of a 49-year-old White woman with neglected large basal cell carcinoma.

Sherrif F. Ibrahim, MD, PhD, and Vishal Patel, MD, FAAD, FACMS, provide initial impressions of the case and discuss the use of immune checkpoint inhibitors.

What's Trending in Skin Care: September 2022

Each month, Dermatology Times® features a roundup of products trending in skin care. Find out what products are trending for the month of September.

ICYMI, this week we had stories about new study data on roflumilast foam for scalp and body psoriasis, dupilumab's FDA approval, the future of basal cell carcinoma treatment, and more. 

The Weekly Roundup: September 26-30

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Each month, Dermatology Times® features a roundup of products trending in skin care. Find out what products are trending for the month of September. 

What's Trending in Skin Care: September 2022 

 Right away, I felt that she had a couple options here. We could potentially do surgery, which would be very invasive. Imaging showed that this was very deep into the subscapularis muscle. It would have been very extensive, debilitating surgery. We talked to her about systemic treatment with hedgehog inhibitors. But to get your high-level overview, how would you characterize this patient’s risk for potential metastatic disease or adverse outcome from surgery or other systemic treatments? What are your initial thoughts when you see something of this magnitude?

 As we mentioned earlier, this is clearly a locally advanced basal cell carcinoma. If you utilize staging risks, this has at least 2 of the high-risk features of being greater than 4 cm and invading deeply beyond the fat. We’re getting into the group of tumors with a high risk of poor outcomes, recurrence, and metastases. If you aren’t used to the European guidelines for staging, assessment scores go from 1 through 5, easy vs hard to treat. Five is giant, [a] deeply invasive clinical disaster. Clearly, when this case walks in the door, you’re first thinking that this is a 5-type case and a multidisciplinary case, where you need to discuss to figure out the [best] option and what the patient wants.

 When surgical oncology met with her and saw the imaging, they said, “Let’s start hedgehog therapy and see how she does.” Her biggest concern was hair loss. She did very well on the hedgehog therapy. She kept her hair. She didn’t get any alopecia. She tolerated it well, with only nuisance adverse effects.

Suppose this patient didn’t respond. Let’s say you’re on maybe a month, 2 months, or 3 months of oral hedgehog inhibitor therapy, or they had progression of disease. What would you consider next as far as systemic treatments?

Starting a patient on hedgehog inhibitor therapy would likely be my first choice as well in this case. It’s first-line treatment for locally advanced [basal cell carcinoma] when surgery is going to be quite extensive. I’d also be worried about potentially some metastatic focus that hasn’t been picked up and being able to get that under control. In this patient, I’d expect to see response, and I believe we have some pictures of how her response occurred. But if that response stopped and she developed other lesions, then the discussion is around whether surgery at this point makes sense or whether we move to immunotherapy.

Cemiplimab therapy makes a lot of sense, depending on how much of a response you’ve seen and if you have small foci to act, add another mechanism to get clearance here. That would definitely enter into our discussion, but then the discussion would become length of treatment and what the risks and adverse effects are. I tell patients with new checkpoint inhibitor therapy that most patients tolerate it really well, but about 10% of patients will have some life-altering adverse effect. They may have to take medication or temporarily be hospitalized and then their dosing is modified. One percent have died from treatment with immune checkpoint inhibitor. That’s a much lower risk than patients who don’t have optimal treatment of their metastatic tumor, but it’s important to think about. Or maybe surgery makes sense in this patient. I’m curious to know exactly what happened with her response and what path you went down.

 First, she had a very rapid initial response to oral hedgehog therapy that lasted on the order of about 3 months. She tolerated it well, but then we noted some progression in the form of regrowth of her tumor. At that point, the areas of regrowth were small enough that they were amenable to Mohs surgery in the office, which we did, and she’s done well now.…

 Just of small foci of tumor. But certainly, if we had done scouting biopsies and saw substantial residual basal cell, in our practice this would be an ideal candidate to start considering systemic immune checkpoint inhibitor treatment with cemiplimab, because this is exactly the type of patient that was enrolled in the trial, that did well in the trial, that failed hedgehog therapy. And now we have this other option, which is fantastic and exciting.

 The other thought process that is important to bring up is that we’ve talked about overall response rate, but with skin cancers, sometimes it’s the durable response and control of tumor growth that can be a more important measure. Because if patients are under control and have quality-of-life improvement, then that may check off the boxes that they need to be functional and to manage with this.

It’s interesting to have surgery around those foci to know whether the hedgehog inhibitor treatment is pushing the tumor to a more squamous potential, and whether that will respond to immune checkpoint inhibitor even higher than those clinical trials for basal cell. These are areas that we’re trying to figure out as more data in these patients are followed out. Or how can we predict whether they will respond to help us move toward surgery or toward immune checkpoint inhibitor at that progression standpoint?

I should also make a plug that at that 3-month mark, the magic number when the adverse effects for hedgehog inhibitor therapy start to rear their ugly heads, there are alternate dosing regimens that have been evaluated in a randomized clinical trial fashion. The…trial that was done mainly in Europe looked at alternate dosing and showed [that] the group that was on treatment for 12 weeks and then had 8 weeks of placebo off treatment essentially had fewer adverse effects and improved response rates compared with patients who were treated for a longer period and then stopped. There are other potential options, but I agree with you. I’d certainly consider moving to immunotherapy with cemiplimab for a patient who progressed after 3 months of hedgehog inhibitor therapy.

 It’s true to say that we’ve barely scratched the surface on understanding where the immune checkpoint inhibitors fit into our management plan. We’re all very excited to have the option, and it’ll be interesting to see how the data unfold over time as more of us refer these patients for this class of treatment.

With that, I’d like to wrap up. I want to thank you again, Dr Patel, for joining us. Thank you for watching this 

 presentation. I hope you found it rich and informative and took away some learning points. Thanks again.

BCC Patient Case Impressions

 Dr Patel, I want to present a case that I recently saw in my practice. It’s a 49-year-old woman. She was referred to me for a neglected large basal cell cancer. We had a long consultation. We talked about the potential for surgery. We talked [about] the potential for systemic hedgehog inhibitor treatment. I made a referral to surgical oncology for her to meet with our local provider. We did some imaging. First, we ordered an MRI, and we revealed that the deep margin of the tumor invaded all the way through the subscapularis muscle. This would make surgery very challenging and difficult.

All of us together, in conjunction with the multidisciplinary tumor board, opted to start systemic hedgehog inhibitor therapy. As is the case with many of these patients, we saw an incredibly rapid response to treatment. The tumor shrank extremely quickly, over just a few weeks, and surprisingly, she tolerated it well. She was very hesitant because of [potential] hair loss and people at work asking questions and so forth, but well into treatment, she didn’t have anything beyond what you would consider nuisance adverse effects.

Interestingly, at about the 4- to 5-month mark, she had progression of the tumor while she was on the drug in the form of small nodules that started showing up within the treatment field. She and I then discussed that there could be tumor everywhere or it could be isolated lesions. I said we’d be able to discover that with Mohs surgery, certainly if we could get around these lesions. She was amenable to proceeding with surgery, so we resected these 2 small nodules with Mohs surgery. They cleared in 2 stages. They were closed primarily, and she did well. A couple of months later, she said, “I’m getting tired of being on oral hedgehog treatment,” and she stopped. Now, many months after any kind of treatment, she has done well, with no clinical evidence of disease.

 Maybe you can sum up in a few sentences where the field has been in the last few years and where it’s going, and then we can finish by talking about one of the cases that I’ve seen in my practice before we wrap it up.

 It’s exciting that we’re seeing the change of focus to harnessing our immune system, at least for the advanced and metastatic cases. We know from what happens to patients who have suppression of the immune system or organ transplants how much skin cancer can wreak havoc on their lives. Now we have 2 options for those patients when surgery can be debilitating or they aren’t able to tolerate surgery.

[We can use] hedgehog inhibitors, the tolerability of which still remains an issue. The main 3 adverse effects—hair loss, muscle pains or taste loss—appear in most patients around the 3-month mark, and there are ways to mitigate that with alternate dosing strategies that may help the patient tolerate that. But when they don’t, immune checkpoint inhibitors are game changers. They are the holy grail to oncology. We’re seeing that across cancer types. We saw that in squamous cell carcinoma at a much higher rate than in basal cell carcinoma. We can discuss why that is. But now we have an option for patients who had nothing. Chemotherapy and radiation aren’t great for this nonresponsive tumor type. We’re excited to see what will come down the pipeline with dual combinations. Checkpoint inhibitor therapy is going to be investigated next, and even potentially intralesional chemotherapy into those tumors instead of systemic infusion.

 It’s exciting to see so many things coming down the pike that work and that will put control in the hands of the dermatologists. The best is yet to come. It’ll be interesting to have this.

 Intralesional is going to be interesting if it comes to fruition. It’s being investigated now. We’re the experts with procedural treatment of skin cancer, so it’s important to get to know this because it may be down the pipeline in the near future.

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