WCM 2024 Conference Highlights

Kicking off our first day of lectures in Miami, Dr Brad Glick reviewed his tips and tricks for treating challenging psoriasis, including when psoriasis ends up being something else entirely. In this case-based presentation, he reviewed therapies for unresponsive palmoplantar psoriasis, comorbidities that may impact treatment of plaque psoriasis and psoriatic arthritis, and a psoriasis look-a-like presenting as exfoliative dermatitis. In the first case, a 74-yo female with palmoplantar psoriatic disease who failed many biologic therapies including secukinumab, ustekinumab, and risankizumab was started on deucravacitinib with remarkable improvement in palms, soles, and scalp psoriasiform lesions. This novel TYK-2 inhibitor can be considered as an “add-on” therapy due to its complimentary mechanism of action to many other biologics and is a reminder that more challenging cases may require compound treatment regimens. In the second case, a former smoker with severe psoriasis, psoriatic arthritis, and a pertinent medical history of valvular heart disease, cerebral aneurysm, and obesity was walked through a variety of treatments with gradually improving responses. While more targeted therapies may have been partially contributing to this patient’s dramatic reduction in IGA, Dr Glick also proposed the importance of weight loss for obese patients with only moderate responses to treatment. Two articles that were cited examine the impact of bariatric surgery and weight loss in general on psoriatic disease. Another pearl in this case is to consider repeating positive QuantiFERON-TB Gold tests before removing patients from successful treatment regimens, as they may be false positives or laboratory errors.  He ended with a case of severe exfoliative dermatitis unresponsive to many different therapies that, after review of an initial biopsy report by a second pathologist, was more consistent with pityriasis rubra pilaris. Islands of sparing were evident in clinical photos, and the patient responded to risankizumab and acitretin. In patients with exfoliative dermatitis, always test for scabies and take a detailed exposure history. 

JAK inhibitors have exploded in the dermatopharmacologic market over the past few years, with myriad disease indications and formulations available. Raj Chovatiya, MD, PhD, started this vigorous session with multiple cases including atopic dermatitis, alopecia areata, and vitiligo, all well suited to treatment with JAK inhibitors. He postulated that the JAK inhibitors work well for numerous dermatologic conditions as, though they themselves are very targeted, the JAK family of proteins impacts many different downstream cytokines. For example, in alopecia areata, MHC Class I expression is increased through JAK 1 and JAK 2, and the activated CD8+ NKG2D+ cells release IFN-gamma, which binds on follicular epithelial cells leading to transition into the catagen phase. JAK inhibitors are perfectly targeted to interfere with the feedback loop that is perpetuated in this disorder. In addition, because they are small-molecule-based treatments, they do not develop immunologic memory like other biologics or theoretical tachyphylaxis. First-generation JAK inhibitors are ATP competitive, meaning they are less inherently selective and have a higher risk of adverse events while they target the highly conserved JAK H1 domain. First-generation JAK inhibitors include tofacitinib, baricitinib, ruxolitinib, and oclacitinib. Second-generation JAK inhibitors are also ATP competitive but are more selective. Conserved adverse effects include cytopenias, hyperlipidemia, and infections. The shared box warning for this class of medications was derived from a 10-year oral surveillance study of patients with rheumatoid arthritis on tofacitinib compared to those on TNF-alpha inhibitors. All of the patients were on methotrexate and many were over 50 years old with more than one cardiovascular risk factor. There was an increased incidence in opportunistic infections, major cardiac events, and malignancy. While this highly conserved evolutionary pathway is important in many pathways, including many that are not related to dermatology, adverse event rates seem to reflect underlying risk factors of the treated population. Dr Chovatiya emphasized the importance of knowing where the warning comes from and how to educate your patients on their own risk to decide if JAK inhibitors are an appropriate treatment.He finalized his talk by driving home the uses of the various FDA-approved JAK inhibitors. Ruxolitinib 1.5% cream is excellent for atopic dermatitis, simplifying complicated treatment routines, and vitiligo, especially in combination with NB-UVB. Abrocitinib and upadacitinib are approved for atopic dermatitis, while the latter has many clinical trials underway for other indications. Both of these JAK1 selective inhibitors demonstrated remarkable responses within 12 weeks of treatment. Baricitinib, a JAK1 and 2 selective inhibitor, was the first JAK inhibitor approved for alopecia areata in the US and is in studies for juvenile idiopathic arthritis. Ritlecitinib shortly followed baricitinib for alopecia areata. Lastly, deucravacitinib, the TYK-2 inhibitor, may be the superior oral option for patients with psoriasis. 

Ruth Ann Vleugels, MD, took us through a review of rarer dermatologic conditions and new therapeutics to be aware of when treating these patients. Starting with DLE, Dr Vleugels reviewed 2 cases that had exhausted the typical treatment ladder from photoprotection through antimalarials and oral steroids and finally to IVIG or rituximab. She presented a promising new drug, anifrolumab, an anti-type I IFN receptor monoclonal antibody, which has recently garnered approval for SLE. However, in the TULIP-2 trial, it showed promising results for CLE as well in patients who had tried and failed many other systemic medications, indicating this may play a role earlier in the treatment algorithm than systemics with more side effects like rituximab. Not only did mucocutaneous lesions show vast improvement, but almost half of patients had more than a 50% reduction in CLASI score, a measurement of cutaneous lupus activity, compared to 25% on placebo (total n=89). Dosing is 300-mg IV every 4 weeks, which has also been successfully used in adolescent studies. She then moved on to reviewing a few different options for dermatomyositis, including IVIG, which demonstrates superiority from placebo within 4 weeks and is now FDA approved for the condition, and tofacitinib, a JAK inhibitor. Larger randomized controlled trials are required to demonstrate efficacy of JAK inhibitors for dermatomyositis, but open-label pilot studies and retrospective studies have shown promising results. Given the strong type 1 interferon signature in dermatomyositis, JAK inhibitors may be a viable option to interrupt this pathway. Dazukibart, a monoclonal antibody directed against IFN-beta, is currently undergoing phase 3 trials for dermatomyositis. Anifrolumab also demonstrates evidence in the treatment of this disease. Lastly, Dr Vleugels reviewed the use of tofacitinib for cutaneous sarcoidosis. JAK inhibitors may be especially useful in treating overlapping autoimmune conditions. 

Rounding out our first day in Miami was a favorite multispeaker session on the newest technologies in aesthetics and regenerative dermatology. Mark Nestor, MD, PhD, started this session with an overview of how he runs a successful dermatology practice by bridging clinical patients into aesthetic referrals and retaining patients. Dr Glaser also encouraged us to use complications from outside providers as opportunities to retain new patients and demonstrate a collaborative clinical manner. She later covered a trending area for cosmetic products and procedures, the neck, which can have a higher risk of complications with energy-based devices. She recommended hyaluronic acid diluted with 0.4 cc of 1% lidocaine for horizontal lines, though bruising can occur, and high-intensity focused ultrasound, which has no downtime. Dr Weinkle demonstrated an injection technique using a cannula for this area as well as the central face. Dr Goldenberg encouraged us to use devices to their fullest potential in our clinical practice, including for diverse indications like acne. Dr Katz also emphasized the importance of reviewing data on devices before incorporating them into clinical practice. His go-to devices are fractional CO2 and erbium lasers, pulsed dye lasers, radiofrequency microneedling, and picosecond lasers. Dr Goldenberg underscored the importance of anxiolytics and cooling devices or NSAIDs in a device-heavy practice to help retain patients. New aesthetic treatments reviewed included a new injectable polypeptide nanoparticle that delivers siRNA to target TGF-B1 and COX-2, leading to apoptosis of adipocytes in novel fat remodeling technology which is now in Phase 1 trials. Dr Katz also showed the mechanism of the new microcoring energy-based device for skin laxity. Another novel device is a bilayer patch with alkali metals to reduce sweat and inhibitor bacteria in the axilla by generating heat when in contact with sweat, thereby inactivating the sweat gland. Dr Glaser showed us how this novel process of alkali thermolysis works with application of under 3 minutes and a peak temperature equivalent to that of a hot tub. Diosmin, a medical food, is a flavonoid covered by Dr Nestor that may be able to improve progressive pigmentary dermatosis, or Schamberg disease, senile purpura, and rosacea by impacting capillaries and vascular wall permeability. Curcumin, a derivative of turmeric that requires specific complexes and processing to become bioavailable, may also help with pigmentation, premature aging, and dark circles by suppressing melanogenesis and tyrosinase activity. Another medical food covered was genistein, which works at the estrogen-beta receptor and is cancer protective, unlike its alpha-type counterpart. It may play a role in improving skin hydration, increasing collagen synthesis, and decreasing bruising and has a small (n=26) RCT that indicated significant improvement in fine wrinkles and elasticity. Lastly, Dr Weinkle covered some practical injection tips like dropping injections of the procerus to be in line with the medial canthus and similarly lowering corrugator injections to avoid frontalis fibers. She cautioned us to avoid zygomaticus major, levator labii alaeque nasi, and the depressor labii inferioris when injecting the masseter, platysma, or orbicularis oris to avoid impacting facial expression. 

The incidence of invasive melanoma is rising, and Dr Darrell Rigel gave us the data we need to contextualize risk for our patients and ensure they receive the most up-to-date treatments. Importantly, in a pooled analysis with data from 2013-2019, 5-year survival rates were significantly worse for African-American patients with localized, regional, and distant melanoma diagnoses giving melanoma the largest racial disparity in survival difference. This trend is reflected in racial and ethnic minorities across other skin cancers and deserves clinical attention.  However, the past decade has also seen advances in targeted therapies and immune checkpoint inhibitors, which likely account for demonstrated improvement in malignant melanoma survival in Italy between 2003 and 2017. Dr Rigel covered who is at risk, especially those subjected to childhood sunburns and frequent sunburns. A less obvious connection was found between those with a family history of melanoma and Parkinson’s disease after following 131,342 patients for many decades. Alcohol consumption also may be a risk factor. While risk factors may provide clinical indication that more information about a lesion is required, the diagnosis of malignant melanoma is not always straightforward and has been quoted to be as low as 65% accurate. Genomics has become an increasingly important tool alongside pathologic findings as atypical genomic data in markers such as PRAME and TERT reflect cellular atypia. Genomic data can further be harnessed to identify patients who are at a higher risk for developing metastatic disease and would benefit from sentinel lymph node biopsies. Dr Rigel walked us through how to understand results from DecisionDx and emphasized the importance of using genomics to optimize clinical care. The last portion of the presentation focused on what happens after diagnosis. In one study, over 3500 patients with sentinel lymph node metastases were randomized to get either immediate dissection or nodal observation with ultrasonography, and melanoma-specific survival at 3 years was similar between groups. Histopathologic regression in patients with metastatic melanoma getting sentinel lymph node biopsies or with metastases on immune checkpoint inhibitors was associated with better survival as was treatment with 2 complimentary immune checkpoint inhibitors, specifically adding relatlimab, a lymphocyte-activation gene 3 inhibitor, to nivolumab, the PD-1 inhibitor. One RCT comparing neoadjuvant-adjuvant and adjuvant-only pembrolizumab in advanced-stage metastatic melanoma demonstrated significantly longer overall survival in those who were treated with the PD1 inhibitor before and after surgery. Other factors that may impact survival are beta-blocker use, statin use, and estrogen levels. He concluded by discussing some exciting innovations like an mRNA vaccine for melanoma for those at high risk of recurrence, which was studied in a Phase 2b trial. 

Dermatology is entering what may be considered a golden age for alopecia areata (AA) with many new treatments available for adolescents and adults alike. While both genders are equally impacted by the condition, it appears that non-White individuals have a higher odds of developing the condition. The prevalence of AA has been increasing for the past 2 decades, and, while genetic predisposition cannot be discounted, Dr Mesinkovska indicated various triggers play a role in the initial loss of immune privilege of the hair follicle leading to destruction by cytotoxic T cells. She launched into the proliferation of treatments for AA, starting with JAK inhibitors bariticinib and ritlecitinib, both of which are approved for the condition. After a review of the JAK/STAT pathway, she covered the real-world application of JAK inhibitors in her practice, indicating the goal is 80% regrowth or a SALT20 in patients who started with complete loss. On baricitinib 4 mg daily, 1 in 3 patients achieve this goal by 36 weeks. Ritlecitinib targets JAK3, which has been shown to be present in skin and lymphoid organs and the TEC kinase family, which consists of 5 members that are involved in intracellular signaling downstream of surface receptors. Regardless, ritlecitinib shows similar results with 43% of patients achieving SALT20 by week 48. Eyebrow and eyelash growth, which for some patients can be more anticipated than scalp hair growth, is slightly higher in ritlecitinib than baricitinib between 40% to 44% compared to 31% to 34%, respectively. The last JAK inhibitor to be aware of is deuruxolitinib which has not yet achieved FDA approval. When discussing JAK inhibitors with her patients, Dr Mesinkovska does not hide the fact that treatment will need to be continued once hair growth is obtained, as stopping or skipping medication can lead to relapse of disease. Those with a disease duration of less than 4 years have the best chance of responding to treatment. The boxed warning for infections, mostly URIs, HSV, and VZV, as well as malignancy and cardiac events, though seen initially in an alternate population using tofacitinib, should be discussed. The hazard ratio for thrombosis is small but should be evaluated in patients with risk factors or those taking OCPs. Other medications to be on the lookout for are probenecid, or other OAT3 transporters, with baricitinib, and CYP1A2/CYP3A inhibitors with ritlecitinib. Isotretinoin and doxycycline can be administered concurrently, especially for those suffering from JAK-inhibitor-induced acne, which is fairly common. She concluded her presentation by presenting a few medication alternatives, including antihistamines, especially in those with atopic background, dupilumab for children or those who are JAK reluctant, and minoxidil in almost all patients to bolster results. 

Dr Lebwohl expounded upon a common clinical question: how to choose a treatment regimen for patients with psoriasis in a world with dozens of biologics and small-molecule inhibitors. In addition to considering pertinent medical history like inflammatory bowel disease or concomitant autoimmune disorders, Dr Lebwohl looks for biologic medications with evidence to mitigate or prevent psoriatic arthritis. He presented data from numerous randomized trials that showed promising results from various TNF-alpha inhibitors and biologics alike. Etanercept inhibited structural damage of joints compared to placebo based on no change from baseline of the Sharp, or van der Heijde, score in one trial, and 45% to 58% of those on secukinumab demonstrated a 20% improvement in ACR, depending on previous TNF-inhibitor exposure, compared to 15% who were on placebo. Ustekinumab, ixekizumab, and bimekizumab demonstrated similar, if not superior, responses, suggesting that IL-17, IL-23, and IL-12/23 inhibitors share this effect. Bimekizumab in particular achieved an ACR20 in 62% of people compared to 68% on adalimumab at week 24. Guselkumab dosed every 4 weeks demonstrated significant improvement in Sharp, or van der Heijde, score, though every 8 weeks did not reach significance. Dr Lebwohl then examined multiple trials looking at the other small-molecule inhibitors’ impact on psoriatic arthritis. He started with apremilast, the oral PDE4-inhibitor, which also showed moderate improvement in ACR scores at both doses at week 16. Known for their quick onset of action, the JAK inhibitor class also has shown benefit for psoriatic arthritis with 70% of upadacitinib users achieving ACR20 at week 12. Deucravacitinib, the TYK2 inhibitor, similarly decreased ACR scores in multiple RCTs. On the other hand, methotrexate has not been shown to prevent joint damage on x-ray. Dr Lebwohl also reported cyclosporine and acitretin as not effective in preventing joint disease. Another variable to consider in some patients, Dr Lebwohl showed us, is weight in obese patients who haven’t achieved adequate response to medications. One trial showed that response to ixekizumab was modified by weight with 75% of those <80 kg achieving a PASI90 compared to 61% of those >100 kg achieving the same response. The difference was even greater for those receiving every-4-week dosing. Response to adalimumab can also be stratified by body weight, interestingly including the placebo group in the CHAMPION trial. For both ixekizumab and secukinumab, the higher doses were more efficacious for patients >90 kg. It appears that almost all of the biologics have evidence for weight-stratified responses. More evidence is required to determine if the same is true for the JAK inhibitor class. 

Sunscreen is a product almost all dermatologists recommend on a daily basis in clinic, and Roger Ceilley, MD, presented what’s going on behind the scenes in this industry as the United States lags behind other countries in available protective UV filters. Currently, the FDA is requiring additional data on a dozen different chemicals to prove them generally safe and effective. More studies are required to determine the quantity of detectable filters in the blood after application before the FDA will give the official approval on many ingredients already approved in Europe, though companies are not required to remove products from the market until the FDA has given their final word on the ingredients within. Of the 17 filters currently approved in the US, 5 are not commonly used, leaving us with 12 compared to almost 30 in the EU. A primary difference between the chemicals available in the US compared to the EU is that we have fewer ingredients that provide protection against UVA1 (340-400 nm), which plays a large role in photoaging, and these include zinc oxide, titanium dioxide, and avobenzone, the last of which still awaits the FDA’s final verdict. It is not uncommon for patients to look for sunscreen abroad where they have access to more filters such as Mexoryl SL/XL/400, Tinosorb S/M, and TriAsorB.  However, Dr Ceilley assured us that new filters in the US are on the way, such as bemotrizinol (BEMT), which is currently undergoing FDA approval and would be the first in over 2 decades. He also presented absorption graphs for TriAsorB, Mexoryl 400, and another novel filter for the EU, BDBP. Moving on to more clinical implications of the sunscreen industry, Dr Ceilley discussed melasma and the importance of photoprotection beyond just sunscreen like photoprotective clothing. The photobiologic impact of visible light has also been a hot topic within the past year, and it, along with UVA1, may aggravate conditions driven by sun exposure like melasma and postinflammatory hyperpigmentation. Tinted sunscreens and oral agents are the best tools against these longer light wavelengths, especially before new filters come to the market. However, tinted sunscreens aren’t as inclusive for all skin types as they should be, especially since Fitzpatrick types IV-VI may benefit more from protection against UVA and visible light, compared to Fitzpatrick types I-III which require UVB protection as well, broadly speaking. An extract from a fern plant native to Central America, Polypodium leucotomos, has been shown to downregulate visible light and UVA1-induced pigmentation and can be recommended as an important adjunct treatment. 

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A much-anticipated session with Drs Del Rosso, Lebwohl, and Zeichner reviewed the hottest new trends and therapeutics for multiple common dermatoses. Starting with acne, results from a clinical trial with the triple-combination gel with clindamycin, adapalene, and benzoyl peroxide were shown, touting a dramatic reduction in inflammatory and noninflammatory lesions by week 4.  For psoriasis, 3-year safety data has been published on bimekizumab, noting 18.5 events per 100 person years in the first year on the IL-17A and F inhibitor. Spesolimab has been shown to decrease flares in generalized pustular psoriasis with those who were started on high-dose spesolimab with a GPPGA score of 0 or 1 remaining flare-free for 48 weeks after week 4 of dosing. Deucravacitinib also has long-term efficacy data from clinical trials, with patients who achieved a PASI75 and PASI90 generally maintaining response for 3 years. The speakers moved on to discuss updates in atopic dermatitis including delgocitinib cream for chronic hand eczema, which tripled those obtaining IGA treatment success by week 8 when compared to placebo. For standard atopic dermatitis, response to abrocitinib may be predicted by week 4, and, for those who don’t achieve an EASI-50 reduction by this time point, dose-escalation to 200 mg should be considered. Tapinarof 1% cream has significant efficacy in children 2 years and up all the way to adults in atopic dermatitis. In a review of novel medications for a few other conditions, the efficacy of roflumilast foam for seborrheic dermatitis, which allowed 79% to obtain IGA success by week 8 compared to 48% using vehicle alone, was covered, along with the improvements of eyelash and eyebrow growth in patients with severe alopecia areata on baricitinib. Deuruxolitinib is another JAK inhibitor undergoing clinical trials for this condition. For chronic spontaneous urticaria, dupilumab improves itch and omalizumab improves sleep. Other advances in dermatology that were covered in this presentation centered around the improvements in gene expression tests. This may lead to advances in difficult-to-diagnose conditions like mycosis fungoides. The 2-GEP assay has a negative predictive value of 99.7%, indicating it can be used to rule out melanoma.  

Joslyn Kirby, MD, walked us through how to manage patient expectations and social perceptions when “prescribing” over-the-counter products in practice. She started with evidence-based treatments for itch, specifically the use of second-generation antihistamines for chronic spontaneous urticaria. While hydroxyzine and lorazepam require prescriptions prior to procedures, diphenhydramine can be kept in the office and used 30 minutes prior at 25-mg to 50-mg dosages for anxiety. She also gave us the recipe for orange juice mixed with 10 x 50 mg naltrexone tablets, which can be dosed in 1-tsp (5-mL) quantities for various pruritus-inducing dermatoses, though patients should be counseled on vivid dreams and headaches.  Dr Kirby had even more hacks for our patients as she presented a study from JAAD that demonstrated that salicylic acid improves the penetration of topical steroids. N-acetyl cysteine functions as a glutamate modulator and antioxidant but has demonstrated efficacy for treatment of picking disorders at 600 mg to 2400 mg daily. If picking becomes pimples, an alternative to antibiotics is zinc gluconate at 90 mg daily for more conservative patients with acne. Pimple patches are also remarkable at keeping hands away from these lesions. Her last pearls are to try out adapalene for acanthosis nigricans, which has more evidence than calcipotriol, and don’t forget to recommend compression stockings, which can be layered at lower strengths for ease of application. 

While many medications exist for the treatment of psoriasis, Dr Armstrong focused this lecture on the new and emerging therapies for this condition. She started with newly approved nonsteroidal topical medications, tapinarof and roflumilast. Interestingly, the former is derived from a species of bacteria within a roundworm with prominent anti-inflammatory properties, and patients treated with the cream demonstrated marked response that was even maintained for 24 weeks after stopping application. Dr Armstrong next reviewed the mechanism of action of deucravacitinib, the TYK2 inhibitor, which modulates the IL-23/IL-17 axis by binding to the more unique regulatory domain of the TYK2 molecule. Patients who obtained PASI75 or PASI90 by week 52 maintained response through an extension study of 3 years, and patients don’t require laboratory monitoring unless they have known liver or lipid disease. Novel IL-23 and IL-17 inhibitors are also under investigation.  Bimekizumab is the newest approved biologic for psoriasis and has demonstrated fast onset and high efficacy with almost 70% of patients achieving a PASI100 by week 16 with noted improvement by week 4. Oral candidiasis is a known adverse event to be prepared for in patients on bimekizumab. She concluded by reviewing generalized pustular psoriasis, which has its first approved treatment with spesolimab. However, another important discussion launched by Dr Armstrong in the discussion of biologic medications is the clarification of biosimilars. They are defined as having identical therapeutic amino acid sequences relative to the reference product and must demonstrate biosimilarity in 3 features: pharmacokinetics, pharmacodynamics, and immunogenicity. She noted, however, that creating consistent identical copies of a biologic is nearly impossible, and dissimilarities exist even from batch to batch within the same manufacturer. Differences in biosimilars may be accounted for in delivery device, product concentration, or citrate content. 

Hidradenitis suppurativa is one of the toughest inflammatory conditions dermatologists treat as it impacts social, psychological, and professional aspects of a patient’s life. Andrea Murina, MD, reviewed oral antibiotics, injectable biologics, and procedures and how to combine them for HS. For long-term maintenance, she recommended spironolactone, metformin, and dapsone. Isotretinoin 20 mg to 60 mg daily is well-suited for patients with evidence of comedones or follicular occlusion phenotypes, while acitretin is good for men and postmenopausal women. Useful additions are zinc 90 mg daily or niacinamide 30 mg daily. Short flares should be managed with oral antibiotics, intralesional steroids, and prednisone if needed. Pain management in HS is another important topic for your patients, and there are a variety of treatment modalities to deploy in treatment. Appropriate wound care, NSAIDs, duloxetine, topical lidocaine, abscess drainage, physical therapy, and even opioids for breakthrough pain may be utilized. Procedural treatments should be considered for both focal and widespread disease in good candidates. Focal disease can be treated with deroofing procedures, Nd:YAG laser, or wide excision, while widespread involvement may benefit from targeting selective areas for excisional surgery in combination with a biologic. Established biologics include adalimumab and secukinumab, which are both FDA approved for HS, and infliximab off-label at 7.5 mg/10 mg per kg every 4 weeks. In 2 RCTs, over 40% of patients on secukinumab achieved at least a 50% reduction in total inflammatory and abscess count by week 16, and over 75% of these patients maintained their response until week 52. However, a few new biologics are on the way including bimekizumab, an IL-17 inhibitor, spesolimab, an IL-36 inhibitor, and various JAK inhibitors. Bimekizumab demonstrated remarkable efficacy with over 50% of patients achieving HiSCR response at week 16 in BE HEARD II at both 2- and 4-week dosing intervals. Draining tunnels improved at week 12 in patients treated with speoslimab, though significant differences were not seen in abscess and inflammatory nodule count. Dr Murina ended her talk with a warning that rising temperatures may increase HS flares. 

Dr Glynis Ablon kicked off our last full day in Miami with an in-depth discussion of 2 popular treatments in hair aesthetics: platelet-rich plasma (PRP) and exosomes. Both PRP and exosomes can act as adjunct treatments to other procedures including with each other. Differentiating between the 2, PRP is an autologous blood component that harnesses the secretory prowess of activated platelets, specifically the alpha-granules they release, which contain growth factors and various other cytokines involved in angiogenesis, remodeling, coagulation, and inflammation. After extraction, PRP remains stable for about 4 hours. Notably, the FDA does not classify PRP as a human cellular/tissue product, and all systems require a 510(k) clearance to be sold. Exosomes, on the other hand, are endogenous nanoparticles released by stem cells to create phenotypic change via growth factors to enhance healing and collagen synthesis, miRNA to regulate gene expression, and cytokine to invigorate cells. Since they include mRNA and miRNA, they have effects long after that of cytokines and growth factors alone.  Exosomes can come purified, which are frozen and contain intact active exosomes, as well as lyophilized in a powder that requires reconstitution, or suspended in a cream. We await studies to demonstrate the integrity of lyophilized exosomes, but they are appealing to consumers in a variety of skin care products. Exosomes also are present in small numbers in PRP and in some plants, though plant-derived exosomes will not bind to human-derived cell receptors and thus efficacy may be limited. Other concerns regarding exosomes include the limited quality control measures, stem-cell sourcing, and the scalability of the extensive and expensive purification process. There also isn’t a set standard for treatment frequency. Unfortunately, as of now, there are few clinical trials involving exosomes related to dermatology, but that may change in 2024. 

Mark Nestor, MD, PhD, took us through a rigorous review of key clinical postulates of botulinum toxin type A to optimize results for our patients and assess properties to discern differences between commercially available products. His first postulate states that all the type A toxins have the same mechanism of action: the heavy chain of the 150kDa active molecule irreversibly binds SV2 receptors on presynaptic cholinergic neurons, leading to cellular uptake, disulfphide bond breakage, and cleavage of the SNAP 25 protein by the light chain to prevent acetylcholine vesicles from fusing with the cell membrane. The rate-limiting step of this cascade of events is the first, SV2 receptor binding. Potency, therefore, is defined by the amount, activity, and affinity of toxin to bind to this SV2 receptor. This is not directly proportional to manufacture units, as lyophilized toxins may vary by 20% within each vial, and daxibotulinumtoxin peptide may prevent aggregation thereby increasing affinity. It follows that increasing the potency may be possible by increasing the number of SV2 receptors, and there is technology looking at additive enhancer toxins for this purpose. The light chain remains active in the cytoplasm for up to 10 months, but the recovery of response leaves many investigators with questions. While muscle mass and age may play a role in differences seen among patients, acetylcholine receptor gene upregulation, proliferation of neuronal axon sprouts, and myogenesis are the least understood parts of toxin response and lifecycle. These myriad factors that influence clinical efficacy are addressed by Postulate II and III, while also bringing in more clinical variables like the distribution of toxin. The efficacy and duration of the effect of botulinum toxin is proportional to the degree of molecular saturation of molecules bound at neuromuscular junctions as well as the time to recovery, but this is difficult to ascertain objectively for commercial products. While each manufacturer uses its own methodology to tout potency results, Dr Nestor recommended comparing independent trial data or results in an individual split-face study. For example, noninferiority trials looking at glabellar lines and the frontalis muscle compare different toxins on contralateral sides of the face. Abobotulinum toxin demonstrated a faster result than onabotulinum toxin for the frontalis, while there was a slight but insignificant preference for prabotulinum toxin compared to onabotulinum toxin for glabellar lines. Postulate V states that increased molecular potency will decrease the time to onset and increase the duration of effect, up until a certain point that is. Diffusion, a passive process that is the same for all toxins, and spread, based on anatomy, technique, and reconstitution, should also be considered when administering toxin. The later postulates consider the impact of diffusion and spread on clinical effect, and while increasing injection sites may allow for optimal spread, the technique comes with more risk of bruising and consumes more time. Looking into 2024, Dr Nestor also mentioned 2 new toxins in the process of garnering FDA approval, letibotulinumtoxin A and relabotulinumtoxin A, the latter of which is derived from clostridium botulinum. Overall, this was a thorough evaluation of one of the most commonly administered injections in the aesthetic domain. 

Gary Goldenberg, MD, focused on regenerative techniques in this up-to-date lecture on nonsurgical treatment of hair loss. He started with platelet-rich plasma (PRP), which harnesses the power of platelet products including growth factors, chemokines, and cytokines to promote cell differentiation and proliferation. Specifically, platelet-derived, vascular endothelial, fibroblast, epidermal, insulin-like, and connective tissue growth factors are responsible for these benefits, which explain this treatment’s usefulness in the treatment of androgenetic alopecia. PRP promotes anagen-associated angiogenesis and neovascularization, dermal papilla cell proliferation, and anti-apoptotic effects. The anagen phase of the hair cycle is extended as dermal papilla cells are protected from premature breakdown. Both dosing at 3 monthly sessions with subsequent injections 3 months later or 2 sessions every 3 months lead to statistically significant increases in hair count, though another trial sponsored by a PRP system manufacturer did show increased hair density with monthly injections compared to quarterly. Further, PRP can be effectively used as an adjunct treatment to many other treatments including microneedling and minoxidil. He moved on to discuss exosomes which are vesicles for intercellular communication, and beyond growth factors, enzymes, and chemokines, also contain mRNA and miRNA. In and of themselves, exosomes could be good or bad, but those used in dermatology are often derived from mesenchymal stem cells, conveying messages to develop into various connective tissues supporting regenerative functions. In hair loss, in addition to the benefits from growth factors and chemokines given by PRP, exosomes also promote hair matrix cell proliferation to revitalize degenerative follicles. Other examples of multipotent stem cells sources are umbilical cord blood and adipose tissue. However, the number of multipotent stem cells present in adipose tissue depends on host factors such as age and general health. Harnessing these cells for hair loss could be in the form of inducing the generation of CK19 positive cells and hairlike structures from mesenchymal stem cells. There are a few small trials that have used adipose-derived stem cells for alopecia, but larger randomized controlled trials are needed.