DAY 2 - DAILY SUMMARY
June 12, 2021

JAAD Highlights from the Last 12 Months

Dirk Elston, M.D.

In this “Best of JAAD” discussion lead by Dr. Elston, we gained numerous clinical pearls. We learned that we do not need to do lab monitoring in healthy adults on terbinafine. Also, we should not to tell our patients to stop anticoagulant therapy prior to dermatologic surgery, but it may be safe for select patients to stop perioperative direct oral anticoagulants.
 
Recent studies on psoriasis showed a reduced mortality of psoriasis patients on systemic treatment. Systemic therapy does not increase risk of hospitalization or death from COVID-19 infection. We also learned that if a patient fails one IL-17 inhibitor, switching to a different IL-17 inhibitor may still be effective.
 
Dr. Elston also gave a shout out to our friend dupilumab: it may be used for prurigo nodularis, bullous pemphigoid, and dyshidrotic eczema. However, we need to carefully follow our patients for the development of CTCL, as few patients have developed or worsened CTCL while on this medication. 
 
Other scary conditions: spironolactone is okay for breast cancer survivors, spouses can help detect melanomas in their partner, and topical calcineurin inhibitors don’t seem to cause cancer. We also learned that blue light from our cell phones doesn’t worsen melasma. There are also emerging treatments for hidradenitis suppurativa, including IL-17 inhibitors, but we should be extremely cautious of the increased risk of inflammatory bowel disease associated with both hidradenitis suppurativa and IL-17 inhibitors.  

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Rosacea and Microbiome of the Skin

Tissa Hata, M.D.

Dr. Hata blew us away with key facts on the skin’s microbiome and its role in rosacea, acne, and atopic dermatitis. 
 
There are several pathways in the pathophysiology of rosacea, including the antimicrobial peptide cathelicidin that converts to LL37, which drives inflammation and angiogenesis. Other key players are demodex, UV radiation, stress, exercise, and heat which stimulate toll-like receptors and neuropeptide release. Many current rosacea medications target these pathways, including the newly investigated metronidazole gel and foam.
 
Regarding the microbiome, those with small intestinal bacterial overgrowth syndrome may be more prone to rosacea. Oral rifaximin, a derivative of rifampin, may help to improve rosacea. We still don’t fully understand the unique microbiome of the skin when it comes to rosacea. We do know that in atopic dermatitis, lesional and nonlesional skin has commensal bacteria with decreased ability to fight S. aureus when compared to controls. In acne, C. acnes appears to be a key culprit in the pathogenesis. This is also the predominant bacteria in sebaceous-laden skin. Certain phylotypes of this bacteria have been implicated in generating reactive oxygen species and inflammation in acne, deep tissue infections, and even medical device infections. Maybe there is role for a vaccine against C. acnes in the future(?!).

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Hyperpigmentation

Pearl Grimes, M.D.

Dr. Grimes gave a wonderful update in hyperpigmentation, which can significantly impact quality of life in patients. 

Melasma has many factors involved in pathogenesis, including increased melanogenesis, solar elastosis,  dermal blood vessels, VEGF expression, mast cells, fibroblast senescence with may upregulate melanogenesis, oxidative stress, and estrogen/progesterone receptors. Patients with melasma have altered barrier function and basal membrane damage leading to melanocyte dropout into the dermis. Thus, melasma is overall thought to represent a phenotype of photodamage.

Post-inflammatory hyperpigmentation (PIH) likely has a genetic predisposition and patients with skin types 4-6 are thought to have more labile melanocytes. Inflammation leads to release of arachidonic acid metabolites and activation of phospholipase A2, prostaglandin E2, thromboxane, leukotrienes C4 and D4, histamine, fibroblast and epidermal growth factors, nitric oxide, interleukin 1 alpha, and endothelin 1, which all lead to melanocyte proliferation, increased melanogenesis, and pigment incontinence. Thus, the treatment involves a multimodality approach with photoprotection, lighteners, antioxidants, exfoliants, moisturizers, and resurfacing procedures.

Recent data suggests that visible light and infrared light may be damaging the skin in addition to ultraviolet light, by causing erythema, free radicals/oxidative stress, mast cell-mediated inflammation, angiogenesis, and hyperpigmentation. Visible light activates the OPN3 receptor on melanocytes which then upregulates MITF and tyrosinase/tyrosinase-related enzymes. Blue light specifically induces formation of a protein complex in dark-skinned melanocytes that upregulates melanogenesis. Iron-oxide containing formulations block more visible light in contrast to other mineral sunscreen ingredients.

Finally, promising non-hydroquinone lightening agents include cysteamine cream, tranexamic acid (oral, topical, intradermal), and Polypodium Leucotomas. Studies on laser/light sources for PIH have found Q-switched Nd:YAG lasers to be most extensively studied with promising results. Low-fluence Q-switched Nd:YAG seems to be the best option for refractory melasma, although IPL also has efficacy, and the fractional 1550/1540 non-ablative laser is approved by the FDA for melasma.

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IL-17 Inhibitors and IL-23 Inhibitors

Jashin J. Wu, M.D.

Dr. Jashin Wu reviewed updates in each of the individual IL-17 inhibitors and IL-23 inhibitors and then head-to-head studies.  In the EXCEED study of secukinumab versus adalimumab for psoriatic arthritis, secukinumab was numerically more effective than adalimumab based on ACR20, ACR50, and resolution of enthesitis, but this was not statistically significant. 
 
Brodalumab has a boxed warning about suicide, but it has yet to be shown to occur in the two-year US pharmacovigilance data report.  In this recent publication, 2677 patients in the United States took brodalumab from 8-15-2017 through 8-14-2019, and there were 0 cases of suicide. 
 
Guselkumab was approved on July 14, 2020 for adult patients with active psoriatic arthritis, which made it the first IL-23 inhibitor approved for both psoriasis and psoriatic arthritis. 
Tildrakizumab showed retention of efficacy from the 5-year pooled data from reSURFACE 1 and reSURFACE 2.
 
In the ECLIPSE trial, guselkumab was shown to have higher PASI 90 responses than secukinumab at week 48. In the IMMerge trial, risankizumab was shown to have higher PASI 100 responses than secukinumab at weeks 52.  In the BE RADIANT trial, bimekizumab was shown to have higher PASI 90 responses than secukinumab at weeks 16 and 48.