Highlights From the 2020 Winter Clinical Dermatology Conference

For the 17th year, the annual 2020 Winter Clinical Dermatology Conference brought clinicians to Hawaii for an immersive multiday learning experience on medical, surgical, and cosmetic dermatology. From January 17 to January 22, attendees gleaned tips from experts in hot topics in dermatology, mingled with industry professionals in exhibits and at industry expert sessions, and enjoyed networking events with peers Other highlights include:

JAK Inhibitors: An Innovation in Treatment
Seemal R. Desai, MD, discussed the latest breakthroughs in janus kinase (JAK) inhibitors and described the potential therapeutic effects of each product.¹

The therapeutic pathway of JAK inhibitors seeks to stop inflammation before it starts. “When you have your cytokine mediator, for example IL-6 or IL-31 in atopic dermatitis or it’s IL-1 alpha or IL-3 in vitiligo, whatever your cytokine is ends up binding to that cellular receptor,” explained Dr Desai. “That subsequently is what turns on that phosphorylation in bringing these two JAK molecules together, which releases the safety signals. Ultimately, when the cytokine binds, bringing these JAK molecules together, that subsequently turns on the recruitment of [signal transducer and activator of transcription proteins], which go into the nucleus and turn on the inflammatory cascade.” JAK inhibitors, however, bind to the kinase domain of JAK to prevent additional inflammation.

The current players include tofacitinib (Xeljanz), indicated for rheumatoid arthritis (RA), psoriatic arthritis (PsA), and ulcerative colitis; ruxolitinib (Jakafi), approved for polycythemia vera and myelofibrosis; and upadacitinib (Rinvoq), which can be used to treat RA. There are several other JAK inhibitors under study:

• Oclacitinib (approved for veterinary use for atopic dermatitis [AD] in dogs);
• BMS-986165 (being studied in phase 2 trials for the treatment of psoriasis and PsA);
• Abrocitinib (phase 3 study on AD just completed);
• Baricitinib (Olumiant; approved in Europe for RA);
• Fedratinib (Inrebic; approved for myelofibrosis);
• Momelotinib (FDA fast-track designation for myelofibrosis); and
• Decernotinib (in phase 2/3 studies for the treatment of RA).

Dr Desai noted that knowing which JAKs are being inhibited by a drug is incredibly important to understanding the safety profile of the drug. “For example, we typically end up seeing more systemic lab abnormalities and issues with blood counts with ruxolitinib than with tofacitinib, and that’s because ruxolitinib blocks JAK2 whereas tofacitinib does not,” said Dr Desai. He suggested performing a blood count, lipid panel, and comprehensive metabolic panel to monitor the patient’s response to a JAK inhibitor. “Generally, if you monitor monthly for the first one to three months, and you don’t see any abnormalities and you’ve kept [the patient] on the same dose, the data is pretty good and you’re likely not to see a major drop in white blood cell count.”

Alopecia areata also can be treated with JAK inhibitors. Dr Desai recommended using topical tofacitinib 2%. Some recent studies, he continued, have shown patients getting on a JAK inhibitor therapy sooner may help with downregulation of transforming growth factor beta and possibly reduce scarring of the hair follicles.

In vitiligo, a lower dose of tofacitinib can be successful. Ruxolitinib cream 1.5% is also effective, but it can cause some adverse events.

Psoriasis has also been studied as a possible target for JAK inhibitor therapy. Most notably, BMS-986165 has been shown to reduce the pathologic hallmarks of psoriasis.

The Rise and Return of Infectious Diseases
Theodore Rosen, MD, reminded attendees to be mindful of infectious diseases in their practice.² As Dr Rosen noted, a number of infections, from sexually transmitted diseases (STDs) to insect-borne diseases, are on the rise at local, national, and global levels.

The session first detailed the resurgence of STDs. For the fifth straight year, the number of STDs has increased in the United States, including a 19% increase in chlamydia, 63% increase in gonorrhea, and 71% increase in syphilis between 2014 and 2018. European countries, such as Iceland, Ireland, the United Kingdom, and Germany, have seen significant increases in syphilis from 2007 to 2017 (876%, 224%, 153%, and 144% increases, respectively).

These stark numbers may be due to the ease of online “hook-up culture” (as Dr Rosen noted, “We can go online and get a sex partner faster than getting a pizza delivered”). However, data from two studies published in JAMA and Sexually Transmitted Diseases found that persons who participate in online dating tend to be better informed through reading crowd-sourced information on STDs and were tested more frequently for STDs.

Viral STDs are still relevant to the dermatologist. For external genital warts, there is no best treatment. “Three papers, looking at meta-analysis of all the common treatments for external genital warts, intended to show the best treatment. They came to different conclusions using the same data,” said Dr Rosen. Considering these three papers along with guidelines released by the European Union, Dr Rosen suggested using a destructive therapy (eg, cryosurgery, carbon dioxide [CO₂] laser ablation) followed by a secondary therapy a week to two weeks later.

Dr Rosen covered HIV, noting two new vaccines: emtricitabine and tenofovir alafenamide (Descovy), and emtricitabine and tenofovir disoproxil fumarate (Truvada). A 2019 study in The Lancet conclusively supported the theory of “undetectable = untransmittable” by demonstrating zero HIV transmissions over a 2-year period when an HIV+ partner reliably took antiretroviral therapy.

The measles outbreak, a hot topic in media, has spread globally. Statistics from the World Health Organization have shown a 300% increase in the first half of 2019 compared with the same period in 2018. This outbreak coincides with the anti-vaccination movement, which stems from religious and personal exemptions. Vaccination laws, which vary by state, often allow these exemptions; Maine, New York, West Virginia, Mississippi, and California currently allow medical exemptions only.

Mosquito-borne infectious diseases are also increasingly relevant to the dermatologist. While dengue, zika, and chikungunya are all well-known, two new viruses are becoming more common. Mayaro virus (of the Caribbean, Central America, and South America) can cause a nonspecific rash along with high fever, pain behind the eyes, arthralgia, myalgia, and more. Parechovirus (found in Japan and Australia) causes a nonspecific or “mittens and booties” rash commonly seen in children less than 5 years of age.

Approaching Abnormal, Inflamed, and Infected Nails
Boni E. Elewski, MD, shared practical tips for dermatologists looking to approach a variety of nail presentations.³

In her first tip, Dr Elewski discussed how diagnosing the solitary abnormal nail can be a relatively easy process. When the patient presents with a solitary abnormal nail, the dermatologist should take steps to determine the differential diagnosis, including biopsy, x-ray, and culture. However, if malignancy is suspected, x-ray should be used first to note of soft tissue growth. Dermoscopy can be especially useful tool for differential diagnosis.

Dermatologists should also pay attention to longitudinal erythronychia. When multiple nails present with longitudinal erythronychia, the underlying cause is an inflammatory process (eg, lichen planus, graft vs host disease, related to a medication). When longitudinal erythronychia is localized to one nail, it is commonly a sign of onychopapilloma, but it can also be glomus tumor, verrucae, warty dyskeratoma, or isolated lichen planus. Cancerous causes include basal cell carcinoma, Bowen’s disease, and amelanotic melanoma.

In short, Dr Elewski said, if only one nail is involved, the abnormal nail is likely to be caused by a tumor.

Dr Elewski’s second tip regarded inflammatory nail disorders. For example, nail psoriasis occurs in up to 78% of patients with psoriasis and is common in patients with PsA and genital psoriasis. It usually involves several nails and both hands.

When dermatologists consider the nail-joint relationship, particularly the distal and proximal interphalangeal (DIP, PIP) joints, the relationship between nail psoriasis and PsA should be no surprise. “It’s helpful, in my experience, when you have an abnormal nail to feel the DIP and PIP joints,” explained Dr Elewski, “and talk to the patient about pain, difficulty moving, morning stiffness, and so forth, to help nail the diagnosis.”

Three additional features to consider in diagnosing nail psoriasis are irregular pitting of the nail plate, salmon-colored patches or oil spots on the nail bed, and onycholysis with erythematous borders.

Lichen planus can occur in the nail bed as well. This often presents with longitudinal nail plate fissures, nail plate thinning, longitudinal erythronychia, angel wing deformity, dorsal pterygium, and anonychia. Treatment of nail lichen planus is paramount and should be considered a nail emergency. Treatment options include intralesional steroids to the nail matrix at the proximal nail fold, intramuscular or oral steroids, and topical treatments with potent corticosteroids and tazarotene. However, when the nail presents with dorsal pterygium, the nail matrix is dead, so no treatment is going to be effective. Notably, one-third of nail lichen planus presentations progress despite treatment.

The final tip shared recommendations for the treatment of various nail infections. Dr Elewski discussed three major infections:

• Onychomycosis—Trichophyton rubrum is the most common isolate. This infection is treated with terabinafine 250 mg daily for 90 days (though dermatologists should be careful regarding T rubrum’s growing resistance), itraconazole 400 mg daily for 1 week per month for 4 months or 200 mg daily for 3 months, and fluconazole 200 mg to 400 mg once weekly (such as on “Fungal Fridays” or “Toes-day”).
• Pseudomonas—A greenish nail is likely a Pseudomonas infection. An x-ray on the chronic infection or on painful nails should be done to rule out osteomyelitis. Treatment options include vinegar soaks, half white vinegar/half isopropyl alcohol drops placed under the nail, ciprofloxacin otic drops, and oral antibiotics. Most importantly, the affected area should be kept dry.
• Candida—A blackish nail, towards a lateral edge with edema and loss of cuticle, may be caused by Candida infection. Treatment includes oral fluconazole 200 mg daily for one week.

Provide Relief for Patients With Urticaria
Mark Lebwohl, MD, addressed updates in the diagnosis and treatment of chronic urticaria and shared some tips for management.⁴

Distinguishing physical urticaria from urticarial vasculitis can be easy when dermatologists consider the clinical signs. Chronic physical urticaria lasts less than 24 hours in any one place on the body and often itches, whereas urticarial vasculitis is often painful and can last for weeks in a single place. Notably, autoimmune diseases, such as hyperthyroidism and hypothyroidism, Celiac disease, and Sjögren syndrome, are more prevalent in patients with chronic urticaria.

Interestingly, diet plays no role in the management of urticaria. Patients often share anecdotal improvement in their urticaria when certain foods are eliminated from their diets, but the literature has not shown improvement. The only possible dietary change that may occur in the presentation of urticaria angioedema, noted Dr Lebwohl, follows the bite of a Lonestar tick, which can induce a red meat allergy through the transmission of alpha-gal antibodies.

A number of treatment options for chronic urticaria exist, but as Dr Lebwohl noted, many are relatively ineffective or unsupported in the literature, including narrowband UV-B therapy, methotrexate, tacrolimus, warfarin, eradication of Helicobacter, and sulfasalazine.

Dr Lebwohl highlighted several therapies that have found some success in the treatment of chronic urticaria. For example, systemic corticosteroids can be an option, though it carries the associated risks of systemic treatment and should be initiated with extreme caution.

Next, Dr Lebwohl mentioned antihistamine H₁ as an effective option. In one 2010 study from the Journal of Allergy and Clinical Immunology, 75% of refractory patients with urticaria responded to a higher dose of antihistamines. “My favorite, because it doesn’t make you sleepy even if you up the dose dramatically, is fexofendadine, which is Allegra over-the-counter,” continued Dr Lebwohl. He explained that fexofendadine can be used up to four times a day without side effects.

Two other options are cyclosporine and mycophenolate. “Cyclosporine clearly works,” said Dr Lebwohl, and he continued to explain that his usual dosage of mycophenolate is 4000 mg per day, though the literature has shown doses as high as 6000 mg per day.

Omalizumab (Xolair) has demonstrated great success for the various phenotypes of urticaria (autoimmune, non-autoimmune, chronic spontaneous, recalcitrant physical, angioedema, antihistamine-refractory). A 300-mg dose can be administered, but dermatologists should make patients aware that the therapy can take 5 days to take effect. While mild to moderate treatment-emergent adverse effects (eg, headache, arthralgia, and injection site reactions) have been documented, omalizumab is well tolerated and safe.

However, Dr Lebwohl emphasized, many dermatologists seem to fear the black box warning associated with biologics. “The number [for anaphylaxis frequency] is 0.2%, but why is that?” he said. “Well, [omalizumab] is treating the symptoms of anaphylaxis. You’re treating wheezing, urticaria, and angioedema. It doesn’t work for a few days…so patients could blame the injection for the symptoms they’ve had all along.” So, the potential side ffects of omalizuma may not be as stressful as the dermatology field fears.

With use of omalizumab, urticaria can recur after a median of 5 weeks, so Dr Lebwohl has patients come back every 4 weeks for a maintenance dose. After 6 months, he suggested making a quick scratch on the patient’s arm; if the patient does not get dermographism, then the injection can be delayed as spontaneous remission may have occurred.

The Latest on Handling Keloids and Scars
Brian Berman, MD, PhD, updated attendees on the latest in treating keloids and scarring.⁵ His presentation covered therapies with the potential to reduce recurrence rates.

The estimated recurrence rate of keloids is 71%, despite careful suturing techniques following excision. Oftentimes, the keloid will grow back larger than its original pre-excision size. Recurrence can be a frustrating experience for patients as well as dermatologists, and it can affect the patient-provider relationship. Multiple previous trials have attempted to study postexcisional therapies to find the best preventative treatment.

One suggested treatment is imiquimod 5% cream. In two studies published in the early 2000s, imiquimod 5% cream was applied immediately after kelo id excision. The cream was then applied once a day for 2 months following the procedure. These two studies found that zero of 11 and one of 15 keloids recurred; these results need additional long-term testing to confirm efficacy due to only a 6-month follow-up period. Another study, which used imiquimod 5% cream immediately following a shaving procedure of the keloid as well as 24 hours afterward, saw three of 20 ear keloids recurred at 1 year and four of 20 recurred in 5 years.

X-ray radiation therapy may also have benefits. A retrospective chart review of 96 keloidectomy with superficial radiation therapy (SRT) over a 1-year period found that 10.4% of keloids recurred, and five of those were considered clinically significant. Consensus guidelines on SRT for nonmelanoma skin cancers and keloids state:

• Multiple fractions of SRT significantly reduces keloid recurrence after postsugical treatment;
• Hyperpigmentation and other adverse events can be reduced by fractionation of the SRT dose; and
• Exposing the keloid or healthy perikeloid skin to a 3000-cGy dose of SRT does not cause skin cancer.

Dr Berman then discussed a number of new and emerging options for existing keloids and scars. The first was laser treatments, including pulsed-dye, fractional, CO₂ laser ablative fractional resurfacing (AFR). “So, we know that using pulsed-dye does help get rid of the pink blush of keloids and of hypertrophic scars,” explained Dr Berman. “But fractional ablative laser may actually help increase the range of motion of scars, especially when they go over a joint.” AFR laser therapy may also help improve topical absorption; this technique has demonstrated improvement in texture but not much improvement in dyschromia. When it comes to planning to use AFR laser with topical corticosteroids, Dr Berman noted this combination therapy is “not a homerun for using it on keloids.”

Botulinum toxin A is also a possible option for surgical scars. In a split-face surgical scar study, half of a scar was injected with saline and the other half was injected with botulinum toxin. The halves that received the toxin were narrower and had significantly lower height scores on the Vancouver Scale.

In the future, Dr Berman explained, that dermatologists will look to control the profibrotic gene expression and translation. One notably theory is to use a mimic of micro-RNA29, which is reduced in fibrotic disorders, because this gene hits six different stops in the pathway of scar formation. In addition, systemic biologics may be a viable option, including:

• Neutralizing IL-17 (secukinumab [Cosentyx], ixekizumab [Taltz]);
• Antagonizing IL-17 receptor (brodalumab [Siliq]);
• Neutralizing IL-6 (siltuximab [Sylvant]); and
• Antagonizing IL-6 receptor (tocilizumab [Actemra]).

A single case report demonstrated success in reducing
keloid appearance by using dupilumab (Dupixent). This patient with severe eczema also had two keloids; after 7 months of 300-mg doses with dupilumab to treat his AD, the patient’s larger keloid shrunk and his smaller one completely disappeared. Future studies, however, are needed to confirm the results and subsequent benefits.

But, in the meantime, clinicians should give their patients a realistic hope to reducing their appearance of their keloids.

References
1. Desai SR. JAK inhibitors: the new breakthroughs in the treatment of dermatologic disease. Presented at: 2020 Winter Clinical Dermatology Conference; Kohala Coast, HI; January 18, 2020.

2. Rosen T. Infectious disease update. Presented at: 2020 Winter Clinical Dermatology Conference; Kohala Coast, HI; January 18, 2020.

3. Elewaki BE. Nail tips. Presented at: 2020 Winter Clinical Dermatology Conference; Kohala Coast, HI; January 18, 2020.

4. Lebwhol M. Chronic urticaria update. Presented at: 2020 Winter Clinical Dermatology; Kohala Coast, HI; January 19, 2020.

5. Berman B. New and emerging treatments for excessive scarring and keloids. Presented at: 2020 Winter Clinical Dermatology Conference; Kohala Coast, HI; January 20, 2020.