Four decades of dermatology advances

Dermatology Times has helped to document some of the specialty’s biggest breakthroughs in the last 40 years. We asked the very dermatologist experts who often help us to report on dermatology milestones to weigh in on what they think made the most difference in theirs and their patients’ lives.

TO TREAT NODULAR ACNE

Isotretinoin (13-cis-retinoic acid), which was approved by the U.S. Food and Drug Administration (FDA) as an oral capsule formulation in 1982 to treat severe recalcitrant nodular acne, has proven to be a major pharmacological breakthrough for acne patients. That’s despite being challenged for its teratogenicity, according to a paper published in 2014 in theJournal of Clinical and Aesthetic Dermatology.¹

“In my view, the most significant advance in dermatology has been the development and use of isotretinoin in patients with severe and recalcitrant acne,” according to Tucson, Ariz., dermatologist Norman Levine, M.D. “This one drug has improved the lives of millions of young people. No other drug or device has come close to matching this success in such a prevalent and potentially devastating skin condition.”

Dermatologists have likely felt the greatest impact among medical specialties from isotretinoin, given acne is one of the most common conditions they treat. Acne ranked first among the top 20 conditions seen by dermatologists from 2001 to 2010, according to an article published in 2014 in Cutis.²

RELATED: New topical retinoid for acne achieves efficacy endpoints

Acne has far-reaching effects on patients’ physical and psychological wellbeing. Isotretinoin enabled dermatologists to prescribe a drug that offered some of the hardest-to-treat acne patients complete clearance, says Miami, Fla., dermatologist Jill Waibel, M.D. “This is a type of result that is unheard of in any medical treatment. Isotretinoin has undergone unwarranted demonization in years past and is finally emerging to its rightful role as ‘the drug that got bullied.’ I encourage all of my severe acne patients to try isotretinoin as long as they are not pregnant or breast feeding, as it is the only current way to achieve not only complete but permanent clearance,” she says. 

AN AESTHETIC GAMECHANGER FOR SKIN: TRETINOIN

While dermatologists have used tretinoin since the 1960s, dermatologists and others didn’t realize the true potential of the retinoid’s impact on aging skin until the 1980s, researchers reported in paper published 2006 in Clinical Interventions in Aging.³

Old Metairie, La., dermatologist Patricia Farris, M.D., says the discovery that tretinoin could be used to treat wrinkles and improve the appearance of aging skin was big news for dermatologists and patients.

“I remember being in the back of the room when they were presenting some of the first studies confirming efficacy and thinking, wow, this is a real gamechanger,” Dr. Farris says. “Up until then, we didn’t really consider topical skincare of value for much beyond moisturization. All of a sudden, we had a cream that patients could apply at home that could actually make them look younger. This really changed the way we thought about skincare and gave way to the development of cosmeceutical products for treating a variety of cosmetic concerns.”

LIGHT ON LASERS

New York City dermatologist Roy G. Geronemus, M.D., says the most significant gamechanger for his practice happened around 1983, when Rox Anderson, M.D., and John Parrish, M.D., published “Mechanisms of Selective Vascular Changes Caused by Dye Lasers”⁴ - the first article on the use of the pulsed-dye laser’s selective photothermolysis.

“This theory of selective injury of vascular targets in the skin has led to transformative treatments for not only vascular conditions, but also for pigmented lesions, tattoos, hair removal, fractional resurfacing for rejuvenation, scar management and laser assisted drug delivery,” Dr. Geronemus says. “The safety profiles of the technologies developed based on this theory have been extraordinary, leading to widespread acceptance. Selective photothermolysis will likely have an increasing impact on a number of medical conditions in the near future.”

The pulsed-dye laser was an evolution for not only adults but also children, according to Tucson, Ariz., dermatologist Ronald G. Wheeland, M.D. “The pulsed-dye laser allowed the treatment of port-wine stains or other vascular lesions in children, even babies, without a risk of scarring or pigmentary changes unlike all previous devices or treatments,” Dr. Wheeland says. “This was revolutionary in that children could start school without any disfigurement - a real gamechanger.”

RELATED: Silicone gel for skin healing

Laser techniques in dermatology have been expanded and optimized to allow rapid, low downtime treatment options for the most stubborn of skin pathologies, with constant progression still underway, according to Dr. Waibel.

ADVENT OF TUMESCENT LIPOSUCTION

Dermatologist Jeffrey Klein, M.D., published his landmark studies on tumescent anesthesia in the 1980s paving the way for this breakthrough to advance patient care, according to Indianapolis, Ind., dermatologist C. William Hanke, M.D., M.P.H. “Tumescent anesthesia allowed liposuction and other dermatologic procedures to be performed safely and effectively on awake patients,” Dr. Hanke says.

NEUROTOXINS HIT THE MARKET

Neurotoxins for cosmetic use started with the approval of onabotulinumtoxinA (Botox, Allergan) in 2002 for moderate-to-severe frown lines, according to maker Allergan.

Before that in 1990, dermatologist Alastair Carruthers and ophthalmologist Jean Carruthers published their first report on the cosmetic use of botulinum toxin type A.⁵ San Francisco dermatologist Seth L. Matarasso, M.D., says neurotoxins have been pivotal in dermatology and dermatologic surgery - for aesthetic and therapeutic indications.

“I’ve been in practice for over 25 years, and I think the introduction of neurotoxins has been nothing short of groundbreaking,” Dr. Matarasso says. “In the aesthetic arena, neurotoxins are safe, reliable and so predictable, and patients are universally pleased with the outcomes. These are just some of the therapeutic indications: migraine headaches, temporomandibular joint syndrome with concomitant bruxism. Just yesterday I treated a 19-year-old boy who was socially ostracized because of profound hyperhidrosis. So, from my perspective, this class of products has had a truly dramatic impact on how we can best treat patients.”

Dermatologists and others are just seeing the tip of the iceberg in terms of potential benefit from neurotoxins, according to Dr. Matarasso.

With years of experience in using these products, dermatologists are realizing the power of neurotoxins and that “a little is good and a lot is not better,” Dr. Matarasso says. The problem is there is little regulation of neurotoxins, and that could put a black eye on its potential.

“This is not a product to be underestimated,” he says.

BIOLOGICS FOR PSORIASIS

Finding the best treatment for psoriasis has clearly been top of mind for many dermatologists. One of the most read and cited articles in the Journal of the American Academy of Dermatology in the past decade has been “Psoriasis causes as much disability as other major medical diseases,”⁶ by Rapp et al, according to Dr. Waibel.

RELATED: Apremilast Appears Safe For Children With Psoriasis

And psoriasis is among the top 10 conditions most commonly seen by dermatologists, according to the Cutis article.

“Psoriasis has become an immensely burdensome disease with increasing focus from the best dermatological minds. The emergence of the first class of biologics, TNF inhibitors, began around 2003 and achieved some success. However, the second class, emerging closer to 2009, which includes [interleukin-] IL-23 and IL-17 inhibitors, has been the true revolution of psoriasis treatment,” Dr. Waibel says. “New biologic treatment has allowed for 95% or even full clearance in the most severe full body psoriasis patients with limited-to-no side effects. Compared with traditional approaches for severe patients, such as methotrexate, cyclosporine and other broad scale immunosuppressants, these medications have a substantially higher safety profile with greater efficacy. Additionally, biologics, systemic reduction of psoriasis-induced inflammation, target cardiac comorbidities, which are known to be elevated in patients with inflammatory disorders.”

Biologics literally changed psoriasis treatment, and for the first time, offered hope and clearance for not only the skin but also the joints, says Medina, Ohio, dermatologist Helen M. Torok, M.D.

The introduction of biologics for psoriasis also has revolutionized treatment for many other diseases, according to New York City-based dermatologist Mark Lebwohl, M.D. “We now treat cancers, rheumatoid arthritis, sarcoid, inflammatory bowel disease, and many others with biologic therapies. Now, all we have to do is make them affordable!” Dr. Lebwohl says.

Psoriasis treatment continues to evolve, according to Dr. Torok.

“I’m Looking forward to the advancement of cutaneous diseases with the [Janus kinase] JAK inhibitors,” Dr. Torok says. “We live in an exciting time in dermatology.”

A FIRST FOR PROLIFERATING INFANTILE HEMANGIOMA

The FDA approved propranolol hydrochloride (Hemangeol, Pierre Fabre Pharmaceuticals) on March 14, 2014⁷ for the treatment for proliferating infantile hemangioma requiring systemic therapy. Hemangeol is the only FDA-approved treatment for the indication.

Infantile hemangiomas are the most common infantile tumor, with a prevalence of infantile hemangioma in mature neonates around 4.5%, according to a recent article in the Pan African Medical Journal.⁸

While most infantile hemangiomas regress spontaneously without therapy, about 10% to 15% of cases have complications.

RELATED: Distribution not random for localized infantile facial hemangiomas

“Therapeutic effect of propranolol over infantile hemangioma was detected incidentally in the year 2008, when regression of facial hemangioma was noted in a child while being treated for hypertrophic cardiomyopathy by this molecule,” the authors write. “Since then, it is being used for infantile hemangioma and currently oral propranolol is the treatment of choice for this condition.”

Hemangeol is among the practice-changers for Saint Louis, Mo., based pediatric dermatologist Elaine C. Siegfried, M.D., whose other picks for biggest dermatology breakthroughs in the last 40 years were isotretinoin, biologics for psoriasis and dupilumab (Dupixent, Sanofi and Regeneron Pharmaceuticals).

“[The advances in dermatology] improve a clinician’s quality of life almost as much as their patients’,” Dr. Siegfried says.

Which brings us to dupilumab for atopic dermatitis.

On March 28, 2017, the FDA approved dupilumab injection to treat adults with moderate-to-severe eczema. FDA later approved dupilumab for patients ages 12 to 17 years.

Dermatology Times recently covered a story about how dupilumab is a game-changer for children, like 13-year-old Benjamin Sun, with moderate-to-severe atopic dermatitis.⁹

Biologic drugs for severe psoriasis, melanoma and non-melanoma skin cancer, and severe atopic dermatitis in the current decade have been among the medical breakthroughs in dermatology, according to Dr. Hanke.

“All of these breakthroughs significantly advanced the care of patients by dermatologists,” Dr. Hanke says.

ACCESS TO INSIGHT

It’s not only the groundbreaking therapies but also the evolution in medical coverage that delivers news about these therapies to dermatologists faster than possible with traditional journals, according to Boston-based dermatologist Ranella Hirsch, M.D., who chose the timely delivery of news as one of the biggest breakthroughs in dermatology in recent decades. “While it is wonderful to read things as they are published in journals, there’s something quite spectacular about getting the scoop on things as they are happening,” Dr. Hirsch says.

References:

1. Leyden JJ, Del Rosso JQ, Baum EW. The use of isotretinoin in the treatment of acne vulgaris: clinical considerations and future directions. J Clin Aesthet Derma- tol. 2014;7(2 Suppl):S3–S21.

2. Wilmer EN, Gustafson CJ, Ahn CS, Davis SA, Feldman SR, Huang WW. Most com- mon dermatologic conditions encountered by dermatologists and nonderma- tologists. Cutis. 2014;94(6): 285-292

3. Mukherjee S, Date A, Patravale V, Korting HC, Roeder A, Weindl G. Retinoids in the treatment of skin aging: an overview of clinical efficacy and safety. Clin Interv Aging. 2006;1(4):327–348.

4. Anderson RR, Jaenicke KF, Parrish JA. Mechanisms of selective vascular changes caused by dye lasers. Lasers Surg Med. 1983;3(3):211-5.

5. Jaspers GW, Pijpe J, Jansma J. The use of botulinum toxin type A in cosmetic facial procedures. Int J Oral Maxillofac Surg. 2011;40(2):127-33.

6. Rapp SR, Feldman SR, Exum ML, Fleischer AB, Reboussin DM. Psoriasis causes as much disability as other major medical diseases. J Am Acad Dermatol. 1999;41(3 Pt 1):401-7.

7. DiscoverHEMANGEOL.PierreFabrePharmaceuticalswebsite: https://www. hemangeol.com/hcp/. Accessed August 2019.

8. Prasad A, Sinha AK, Kumar B, Prasad A, Kumari M. Individualized dosing of oral propranolol for treatment of infantile hemangioma: a prospective study. Pan Afr Med J. 2019;32:155.

9. Hilton L. A game-changer for children with atopic dermatitis. Dermatology Times. 2019;40(5):1, 20-21.