This month’s news from across the specialty

June 1, 2022

In this monthly column, members of the DermWorld Editorial Advisory Workgroup identify exciting news from across the specialty.  

A recent study compared lipidomes and transcriptomes of single cell dermal fibroblasts to explore the determinants of cell fate (Science. 2022. April 15;376(6590): eabh1623).

The study overcomes the central obstacle that single cells are obliterated by the distinct methods of characterizing mRNA and lipid populations — limiting direct comparisons — by quantifying 205 lipids in 257 single cell dermal fibroblasts by vaporizing them by lasers and analyzing the plume mass spectrometry. Lipids segregated in clusters within different cells that suggested four distinct lipid metabolic states for groups of cells referred to as lipotypes. Lipotypes were further confirmed to be self-perpetuating independent of the transcription levels of lipid-regulating genes.

Next, 5,652 dermal fibroblasts were interrogated with single-cell RNA sequencing and organized into six categories: proliferation, fibrogenic, fibrolytic, inflammatory, vascular, and basal. While the four lipotypes are spatially associated with the six categories of transcription, the associations diverge from the lipid profiles expected from the expressed mRNA of lipid modifying enzymes. Further, manipulation of specific lipids in live cells was shown to impact cell states. Everything determines cell fate.

When you add up all we know about anatomic variation of the skin, transcription, and post-transciptional modifications, these results make sense and are what we might have predicted. We know the dermis of the eyelid is distinct from the dermis of the back. The individual fibroblasts incorporate a multitude of signals to collaborate with their neighbors to be anatomically appropriate.

Lipotypes provide legacy information about lineage that can only change slowly over generations of cell divisions. I find comfort in these redundancies of cell fate determination.

The contact allergen of the year is a hot topic for all of those in the world of contact dermatitis. This honor has been given each year for over 20 years to an allergen of new or emerging significance and sometimes — in the case of thimerosal, gold, and parabens — to allergens of non-significance.

The honor for 2022 goes to aluminum (Dermatitis. 2022: 33(1):10-15). Aluminum is a metal that most of us are exposed to routinely. Aluminum salts are present in food, vaccines, antiperspirants, and other consumer products. Contact allergy to aluminum is not felt to be common, though standard patch test trays do not routinely test for aluminum. The modes of sensitization appear to be allergen-specific immunotherapy (ASIT) preparations and vaccines containing aluminum. The main clinical presentation of aluminum reactions from ASIT and vaccination exposure is subcutaneous nodules at the site of vaccination or ASIT sites. These are pruritic nodules that can last for many months and sometimes years. Contact allergy to aluminum can also present with dermatitis from aluminum-containing sunscreen and axillary dermatitis from aluminum-containing deodorants.

Patch testing for aluminum should be done with aluminum chloride hexahydrate (ACH) in petrolatum. It is felt that the ACH 10% concentration detects more aluminum allergy than ACH 2%. A delayed patch test read should also be done at week one, so as to avoid missing 15-20% of aluminum allergy. Patch testing with aluminum can vary over time so if aluminum allergy is strongly suspected and patch testing is negative, retesting over time should be considered.

Editor’s note: Read this issue’s Clinical Applications for more on the 2022 contact allergen of the year.

The insurance transition from employer-sponsored insurance/exchange plans to Medicare for older adults in the United States is not uncommonly fraught with angst for patients. For patients with inflammatory skin disease, including psoriasis, atopic dermatitis, hidradenitis suppurativa, among others, one of the greatest sources of concern we hear from our patients is: how will this transition impact coverage of my most important medications? While almost all outpatient medications used for an FDA-approved indication are included on Medicare Part D formularies, out-of-pocket costs for patients can be astronomical and prohibitively expensive for medications with a high list price. Although low-income beneficiaries can qualify for co-pay subsidies, these subsidies are reserved for individuals with an income less than or equal to 135% of the federal poverty line (or assets up to $9,470) for full subsidy and an income between 135-149% of the federal poverty line (or assets up to $14,790) for partial subsidy.

Overall, most Medicare beneficiaries do not qualify for co-pay subsidies under these guidelines. The sheer magnitude of this problem was captured powerfully in a recent Health Affairs paper that explored “noninitiation” — defined as failure to start treatment with a newly prescribed drug for high-priced specialty Part D drugs in four disease areas: cancer, hepatitis C, immune system disorders, and hypercholesterolemia, across 11 health systems. The study captured 17,076 new prescriptions with 5,286 of these prescriptions being for “immune system conditions” (medications including adalimumab, apremilast, etanercept, guselkumab, ixekizumab, secukinumab, and ustekinumab, among others). Noninitiation among all Medicare beneficiaries was found to be 54.2% for immune system drugs. Noninitiation level was higher for beneficiaries who did not qualify for low-income subsidies. For immune system disorders, noninitiation was 39% less likely for beneficiaries who did not qualify for a subsidy. Legislative fixes to address skyrocketing out-of-pocket outpatient prescription costs for Medicare beneficiaries are crucial to preserve access to life-changing medications and improve outcomes for our elderly population. As dermatologists, our voices are essential in ongoing advocacy efforts in this battle.

I certainly feel like I am dating myself when I tell my residents that upon my own residency graduation, I only had four biologic treatments for psoriasis that I could offer my patients. In stark comparison, our progress in finding novel treatments for alopecia areata (AA) has lagged far behind.

It is with great interest that I read about two phase 3 trials of baricitinib for alopecia areata (BRAVE-AA1 and BRAVE-AA2 trials), together enrolling 1,200 patients. Baricitinib is an oral, selective, and reversible JAK1 and JAK2 inhibitor. These studies enrolled adults with severe AA who had a Severity of Alopecia Tool (SALT) score of 50 or higher (0 = no scalp hair loss, 100 = complete scalp hair loss). The primary outcome was a SALT score of 20 or less at week 36. Patients were randomly assigned to receive baricitinib 4 mg daily, baricitinib 2 mg daily, or placebo. The percentages of patients with a SALT score of 20 or less at week 36 were: 38.8% with 4 mg baricitinib, 22.8% with 2 mg baricitinib, and 6.2% with placebo in BRAVE-AA1, and 35.9%, 19.4%, and 3.3%, in BRAVE-AA2, respectively. Overall, side effects were deemed to be mild or moderate in severity. More common side effects in the baricitinib treatment group included acne, elevated creatine kinase, and increased levels of LDL and HDL.

Current trials are ongoing with the plan to remain randomized and blinded for up to 200 weeks to better assess efficacy and safety. Stay tuned!

Additional DermWorld Resources