California dermatologist pioneers a simple, non-prescription treatment for atopic dermatitis | National Eczema Association

https://nationaleczema.org/orliderm/

While not a cure, Orliderm™ has brought relief to hundreds of children and adults with moderate to severe atopic dermatitis.

Joey's hand after 1 week of Orliderm

Orliderm™ began with an idea.

Ten years ago, Dale Pearlman, MD, a dermatologist who practices in Menlo Park, California, happened to see a TED Talk by a postdoctoral fellow at Princeton University who presented her research on a phenomenon called biofilm.

A slimy matrix of cells and sugars that stick to surfaces, biofilm is produced by many species of bacteria. It's is a "safe haven" that shields bacteria from attack, whether by the immune system or by antibiotics.

Pearlman started to read everything he could get his hands on about biofilm, and eventually, he developed a hypothesis. People with AD have more of a type of harmful bacteria on their skin called Staphylococcus aureus or "staph." And when not kept in check, staph can cause serious infections. That much is obvious, he said.

But if these microbial offenders are foiling our efforts to eliminate them by hiding in slime, they'll never fully disappear, even when treated with the strongest antibiotics. To take them out permanently, he reasoned, you'd need a treatment capable of dissolving the biofilm where bacteria are hiding in plain sight.

Dr. Dale Pearlman decides to put his theory to the test

On the clinical faculty of Stanford University for 25 years, Pearlman was drawn to pediatric dermatology early on. "I've seen lots of kids with eczema over the years, and I had a strong desire to help them," he said.

"I understood the incredible weight of the condition on children and families. No one sleeps. Kids with eczema are constantly itchy and stressed, while their siblings who don't have it may feel neglected by their parents. It's a disease that distorts the family unit."

Determined to make a difference, he started to explore a new approach. He decided to try combining hand sanitizer with a thick steroid ointment. Ethanol—also known as ethyl alcohol—is the ingredient in hand sanitizer responsible for killing bacteria, and the steroid ointment works quickly to cool inflammation. It also prevents the ethanol from stinging.

At first, Pearlman used prescription-strength topical steroid in his formulation but quickly discovered that only a little bit of it was needed to knock out the inflammation.

More fine-tuning led him to experiment with cortisone cream vs. ointment, and ointment won that contest hands down. "The ethanol-cortisone combination only works in the form of an ointment," he explained.

"In ointment, the combined ingredients form hundreds of tiny bubbles – and these bubbles need to be there for the treatment to work. If you mix the ethanol with cream instead of ointment, the bubbles will disappear within 90 minutes after applied to the skin, which isn't long enough for them to penetrate. But in cortisone ointment, the bubbles will stay put long enough to destroy the bacterial biofilm on eczema skin."

Dr. Dale Pearlman

In 2018, Pearlman completed a small, controlled pediatric clinical trial comparing the efficacy of his combination ointment, containing 1% hydrocortisone ointment plus ethanol gel, to 1% hydrocortisone ointment alone.

In one week, the children treated just with hydrocortisone ointment showed a 41% improvement in their SCORAD scores, while those who received Pearlman's combination ointment improved by an average of 74 %.

(SCORAD stands for scoring atopic dermatitis. It is the main tool physicians and researchers use to measure the severity of AD.)

Pearlman's peer-reviewed study was published in the National Society for Cutaneous Medicine's professional journal in January 2019. He is currently seeking support for larger trials that could provide the necessary evidence to confirm his hypothesis and take Orliderm to the next level.

An inexpensive topical with widely available ingredients

"Orliderm seemed almost too simple to be true," said **Carol Roberts, whose 2-year-old son **Joey has severe eczema, "but it has turned out to be a godsend." In May, Roberts found her way to Pearlman, who gave her several jars of Orliderm, and the product relieved her son's symptoms in just one day.

Joey's hand before Orliderm treatment

"Nothing ever worked before," she said, listing all the prescription and over-the-counter (OTC) medications she had used on Joey's skin since his eczema erupted at just 3 months old, from thick moisturizers to topical steroids and moving along to prescription steroids.

She also tried to deal with her toddler's allergies to milk, fish, eggs and nuts in an effort to tame his eczema. Avoiding food triggers proved worthwhile as a way to stave off allergic reactions, but her son's eczema wouldn't budge.

Now that Joey is doing well with Orliderm, Roberts no longer needs to defend herself against well-meaning but baseless accusations that she is somehow responsible for her son's condition.

Joey's hand after 1 week of Orliderm

"Complete strangers would come up to us and ask, 'What happened? Did he fall down?' That hasn't happened for weeks. I'm incredibly grateful to Dr. Pearlman for changing our lives so much for the better."

Orliderm is only one step in a three-part treatment plan

Pearlman goes the extra mile to make his treatment available to parents who tend to be afraid of prescription steroids, immunosuppressants and other strong medications. "They're also busy," he said, "and they're looking for something that's easy to use."

Orliderm fits that bill, he explained. Parents can even learn to mix it themselves by following the instructions on the Orliderm website.

However, the ointment alone isn't enough. On the product's website, Pearlman spells out a three-part treatment, insisting that parents as well as teenage and adult patients follow it to a tee:

• Use Orliderm as specified on the website.

Pearlman provides clear instructions for buying his product's ingredients and mixing them appropriately, along with a link to Amazon.com that offers a complete Orliderm "package," including hand sanitizer, 1% hydrocortisone ointment, mixing sticks and specimen cups.

Dosage is also critically important. Orliderm needs to be applied three times in a row to work properly. Per Pearlman's instructions, rub it in until it penetrates the skin and disappears. Then, repeat. And do it again a third time, after which it will look greasy, and wipe off the excess. Follow this procedure twice a day.

• Bathe the right way. For Pearlman, that means using plain water and keeping soap to a minimum. The water-only approach will help to prevent the irritating and drying effects of soap while preserving the oils in the skin. Of course, soap can be used when necessary—just not all over the body or on inflamed skin.

• Dress the right way. Avoid wearing too many layers of clothing. That will prevent the body from overheating. This arm of Pearlman's treatment is especially important for children, whose ability to regulate their own body temperature is not fully developed. Increased body heat means increased blood flow to the skin, which aggravates eczema.

For the treatment to be effective, Pearlman emphasized, parents should make sure not to skip any aspect of the program. "If it [doesn't work], it will be because a parent substituted cream for ointment," he said, "or because of over-bathing their child with soap.

"Overdressing is the third no-no," he continued. "Whatever you're wearing, dress your child with one fewer layer."

Remember, Orliderm is a treatment – not a cure

Pearlman is the first to insist that Orliderm is not a cure for eczema. In his experience, most children eventually outgrow the condition's worst symptoms, but in the meantime, it typically comes and goes unpredictably. No matter which treatment you use, he said, when you stop using it, eczema's maddening rash and itch will inevitably return.

That's a good argument for giving Orliderm a try, Pearlman added. It's safe and inexpensive, plus it appears to ease the symptoms of eczema that keep families up at night. Joey's parents couldn't agree more. "Sometimes, the simplest treatment turns out to be the best one of all," Roberts said.

** Names have been changed at the request of the interviewee.

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Son necesarios los tónicos Faciales?

Es una pregunta frecuente y la Dra. Zoe Diana Draelos nos comenta:

Are facial toners necessary?

Toners are present in most commercial skin care regimens and are either sold through cosmetic counters or dermatologist dispensed. I am frequently asked whether toning is necessary for skin health. No, toning is not necessary for skin health.

Toners were originally developed to remove soap scum from the face when lye-based soaps combined with hard water left a sticky residue post cleansing. The alcohol-based toner removed the soap scum eliminating irritation and contributing to cleanser mildness.

Today, few people use lye-based soaps and hard well water, so the original use for toners is gone, but the product persists. Toners, also known as astringents, are liquid cosmeceuticals with tremendous formulation diversity. As mentioned previously, an alcohol-based astringent can be used post-cleansing to remove any persisting waterproof makeup residue.

Some may use the toner alone in place of a cleanser. Others may use an oily skin toner to remove any sebum left behind following cleansing to produce a clean, tight feeling many patients find desirable.

Medicated astringents are popular with acne patients based on salicylic acid and may contain sensates, such as menthol or camphor, to create a tingling feeling when applied to the skin.

Dry skin formulations largely contain propylene glycol and water to act as a humectant moisturizer attracting water to the skin, which can be trapped in place by a subsequently applied moisturizer.

Toners can be designed for special use purposes. For example, in an anti-aging routine, a toner may contain an alpha hydroxy acid to induce exfoliation. Glycolic acid is most commonly used because it can be inexpensively synthesized by combining chloroacetic acid with sodium hydroxide followed by re-acidification.

Another cosmeceutical toner variant is a two-phase toner which consists of a solvent and an immiscible oil without an emulsifier. In order for the water-soluble and oil-soluble phases to mix, the product is shaken immediately prior to use. This creates a temporary emulsion prior to facial application.

The water-soluble solvent dissolves the skin soils while the oil leaves behind a moisturizing film for amelioration of dry skin. Glitter can be added into the phases creating interesting optical effects when shaken which adds to the market appeal.

https://www.nature.com/articles/d41586-019-02295-z?utm_source=Nature+Briefing&utm_campaign=5e2fd2a973-briefing-dy-20190729&utm_medium=email&utm_term=0_c9dfd39373-5e2fd2a973-43330245

The 11-step guide to running effective meetings

The quality and outcomes of meetings can improve drastically with a few simple steps.

29 July 2019

CAREER COLUMN

Nadine Sinclair

Credit: Getty

We all know what a bad meeting looks like.

You are on your way to the meeting room, but you have no idea what the meeting is about.

You are in the meeting asking yourself, "Why am I here?"

The conversation gets hung up on details or gets sidetracked entirely.

People are looking at their phones or working on their laptops during the meeting.

The meeting seems to drag on and on although it was supposed to end 20 minutes ago.

There are plenty of people in the room, but not the decision makers.

After the meeting, you feel no closer to the answers you were seeking.

You leave the meeting unsure of whether anything was decided.

Collection: Research leadership

There are ways to combat these problems. Running effective meetings is a skill that can serve you throughout your career. Here is an 11-step guide to doing just that.

1. Do you need a meeting?

Before you move ahead with an in-person meeting, ask yourself if your goals can be accomplished more easily with an e-mail or a phone call. If so, avoid organizing a meeting — be protective of your own and others' time.

Before the meeting: set expectations

2. Define the objective

The first step to a good meeting is defining the meeting objective — the 'why'. This will aid in keeping the discussion focused and will help to measure the success of your meeting.

If you're certain a meeting is necessary, determine its aim. Most meetings belong to one of four categories, each of which has a distinct objective:

Decision-making: the aim is for decision makers to come to a conclusion that leads to action, such as deciding to change an experimental set-up.

Information sharing: the objective is to spread awareness to a broader team, for example by sharing your latest experimental data.

Problem-solving: the goal is to crowdsource advice and build a plan based on that knowledge, such as by discussing ways to optimize an experimental set-up.

Discussion: the purpose is to exchange perspectives on a topic, such as by discussing the implications of a recently published paper.

3. Set an agenda

Vague discussions on a topic rarely achieve anything, and an agenda will ensure that you cover the specific aspects needed to reach your meeting objective. At the same time, it will inform and set expectations with attendees. It is the 'what' of your meeting.

Your agenda might have only a few items. That's perfectly fine as long as it is clear how each agenda item relates to your desired objective; keep your goals specific and declarative.

4. Keep it short

Your meetings should be as long as necessary but as brief as possible. Reserve five minutes at the end to summarize the discussions and agree on any next steps.

5. Get the right people in the room

Before sending out an invitation, take some time to consider who should attend the meeting. It is tempting to be inclusive, but sometimes having more people in the room makes meetings harder. Think of the minimum number of people that you need to achieve the meeting objective. Make sure that the people who are essential to your meeting are aware of their roles.

6. Circulate materials

In addition to sending an invitation stating the objective and the agenda for the meeting, circulate relevant materials at least one day before. Receiving materials in advance allows attendees to prepare for the discussion and is an opportunity to remind them of the meeting and its objectives.

Careers toolkit

During the meeting: keep the focus

7. Start on time, end on time

Time management is an essential aspect of running productive meetings. Start and finish your meeting on time, and keep an eye on the agenda and the clock.

8. Guide the discussion and manage disruptions

Guiding the discussion and managing disruptions are probably the most challenging parts of running a meeting, especially if you are not the most senior person in the room. Your role is to keep the discussion focused so that you can meet your objectives.

A helpful technique for guiding a discussion is to capture important points on a board and mark them as subsequent agenda points or flag them for a follow-up meeting. You might say, "This is beyond what we are here to discuss today. Let me capture it on the board for our next meeting." This way, your attendees feel acknowledged, but you do not let them sidetrack or disrupt your meeting.

9. Summarize decisions and next steps

Make sure you take notes throughout the meeting. It can help to have a printout of your presentation so that you can capture the main discussion points as they come up. Wrap up at the end by summarizing the main points and decisions as well as any next steps you agreed on.

After the meeting: manage the follow-up

10. Circulate the meeting debrief

Your meeting notes will be the basis for a debrief to be circulated among attendees, summarizing the discussion points, decisions made, next steps and topics earmarked for future discussions. For the next steps, make sure that you include the responsible person as well as the agreed deadline. A best practice is to circulate the debrief within 24 hours of the meeting to keep the momentum going. If there's nothing written down, then the results of a meeting can fade into nothing.

11. Follow up on action items

Last but not least, follow up individually on the action items if needed.

Even if you are not in charge of running meetings, sharing some of the above points with your colleagues or using these guidelines to initiate a discussion can be the first step to making meetings more effective in your research group.

doi: 10.1038/d41586-019-02295-z

This is an article from the Nature Careers Community, a place for Nature readers to share their professional experiences and advice. Guest posts are encouraged. You can get in touch with the editor at naturecareerseditor@nature.com.

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WCD 2019: Two-Year Study Confirms Long-Term Benefits of Risankizumab in Psoriasis | PracticeUpdate

WCD 2019: Two-Year Study Confirms Long-Term Benefits of Risankizumab in Psoriasis

June 14, 2019—Milan, Italy—Risankizumab provides a durable response for psoriasis in a trial that followed patients on continuous therapy for up to 104 weeks. The findings were presented here at the 24th World Congress of Dermatology, which took place from June 10 to 15.

Risankizumab is a humanized IgG1 monoclonal antibody that selectively inhibits interleukin (IL)-23 through binding p19. It was recently FDA-approved in the United States for use in psoriasis. It is also approved by the European Medicines Agency for this indication.

"Targeting p19 has shown higher levels of efficacy [in psoriasis], as high or higher than biologics that have already been on the market," study coauthor Melinda Gooderham, MD, of Queen's University School of Medicine in Kingston, Canada, told Elsevier's PracticeUpdate. "The nice thing is that, with the higher levels of efficacy, you don't compromise safety. You have a clean safety profile. There are no new concerns. If anything, there are fewer safety concerns than we see with the current biologics on the market."

IMMhance was a two-part, phase III, multinational, double-blind study in patients with moderate-to-severe plaque psoriasis. In the first part of the study, after 16 weeks of treatment, a greater proportion of the 407 patients treated with 150 mg of risankizumab met the coprimary endpoints of Psoriasis Area and Severity Index (PASI) 90 and static Physician's Global Assessment (sPGA) 0/1, compared with the 100 patients on placebo (P < .001).

In the second part of the trial, led by Andrew Blauvelt, MD, of the Oregon Medical Research Center in Portland, responders to initial risankizumab treatment (defined as an sPGA 0/1) at week 28 were stratified by weight and prior TNF inhibitor exposure and then re-randomized in a 1:2 fashion to continuous risankizumab every 12 weeks (n = 111) or to placebo (n = 225). After week 32, patients who relapsed, as defined by an sPGA ≥ 3, were re-treated with open-label risankizumab 150 mg. The primary and ranked secondary efficacy endpoints were the proportion of patients who maintained sPGA 0/1 at weeks 52 and 104, respectively, using non-responder imputation. Safety was also assessed in all patients.

At week 52, 87.4% of patients re-randomized to continuous risankizumab maintained sPGA 0/1, and 81.1% maintained it at week 104. In contrast, sPGA 0/1 was maintained in 61.3% of placebo at 52 weeks and 7.1% at 104 weeks (P< .001 for both time comparisons).

By week 94, 73% of patients receiving continuous risankizumab had completely clear skin, defined as an sPGA 0. "That's the highest level of sPGA 0 we have seen with any biologic," said Dr. Gooderham. "Usually, we see a bit of a drop-off as you lose efficacy in some patients over time, but we did not see that with this medication. We saw the levels increasing, with more patients becoming clear the longer they were being treated. … [And] we know from many other studies that patients with [completely] clear skin have a better quality of life."

Overall, 153 of the 225 responders at week 28 who were re-randomized to placebo experienced relapse (68%). After 16 weeks of risankizumab re-treatment, 83.7% of these patients regained sPGA 0/1.

Risankizumab was well-tolerated. Safety was generally comparable in the continuous-therapy and the placebo groups.

"This is a chronic condition, … a disease that people suffer with for decades," said Dr. Gooderham. "If week 16 results look great, but in 2 years they are losing response, that is not helping us out in the long run. So, with therapy where we see patients staying clear and more patients becoming clear over time, we can be sure their chronic disease will be controlled chronically. … We shouldn't have any tolerance for psoriasis hanging around [anymore] now that we know we can clear it with such high levels."

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Psychiatric Adverse Events in Patients Taking Isotretinoin | PracticeUpdate

Published in Dermatology

Journal Scan / Research · July 23, 2019

Psychiatric Adverse Events in Patients Taking Isotretinoin

JAMA Dermatology

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• In this review of 17,829 psychiatric adverse event associated with isotretinoin use reported to the US FDA between 1997 and 2017, depressive disorders (42.3%), emotional lability (16.6%), and anxiety disorders (13.5%) were most common. These adverse events occurred most often in the 10- to 19-year-old age group (52.5%).

• In 2009 and 2010, the rate of completed suicides in patients taking isotretinoin was 8.4 and 5.6 per 100,000 patients, respectively, which was lower than that for the general US population during those years (11.8 and 12.1 per 100,000 individuals in 2009 and 2010, respectively). Other reported events included insomnia, self-injurious behavior, and psychotic disorders. The authors suggest a screening tool such as the Patient Health Questionnaire-2 to screen for depression at each monthly visit for all patients on isotretinoin therapy.

– Caitlyn Reed, MD

http://www.practiceupdate.com/content/psychiatric-adverse-events-in-patients-taking-isotretinoin/86229

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Distribution of high-risk α-genus human papillomavirus genotypes impacts cutaneous neoplasms | DocGuide

Source: J Eur Acad Dermatol Venereol  |  Posted 5 days ago

Distribution of high-risk α-genus human papillomavirus genotypes impacts cutaneous neoplasms; Aoki R, Clanner-Engelshofen B, Charnowski S, Ruzicka T, Reinholz M; Journal of the European Academy of Dermatology and Venereology 33 (7), 1304-1311 (Jul 2019)

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BACKGROUND High-risk α-genus human papillomaviruses (α-HPVs) are linked to cervical and genital carcinomas; however, their correlation with cutaneous squamous cell carcinoma (cuSCC) or premalignant skin lesions remains controversial.

OBJECTIVE We evaluated the contribution of high-risk α-HPV to the occurrence of cuSCC, Bowen's disease and actinic keratosis (AK), and the distribution of high-risk α-HPV genotypes in these cutaneous tumours.

METHODS HPV genotypes were determined using a commercial PCR-based microarray on skin tissue samples collected from 76 [38 young (<60 years) and 38 elderly (>60 years)] cuSCC, 34 Bowen's disease, 48 AK patients and 10 young controls. Associations between α-HPV prevalence and relevant risk factors were analysed.

RESULTS High-risk α-HPV was more frequently detected in cuSCC patients (57.9%) than in the patients with Bowen's disease (38.2%), AK (0.0%) and control patients (10.0%). The high-risk α-HPV prevalence was higher in young than in elderly cuSCC patients (65.8% vs. 50.0%, P = 0.031). The most common HPV type was 16, present in 90.9% of all HPV-carrying cuSCC patients. Multiple infections with different high-risk α-HPV types were found in 20.5% of HPV-related cuSCC, whereas only single infection with type 16 was found in Bowen's disease. Although sun exposure is known as a major risk factor for cuSCC, high-risk α-HPVs were more frequently found in non-exposed sites rather than in sun-exposed sites of cuSCC.

CONCLUSION Multiple infections, as well as single infection with high-risk α-HPV may link to cuSCC. In spite of the involvement of high-risk α-HPV at high levels in cuSCC and Bowen's disease, no high-risk α-HPV was detected in AK patients, suggesting that Bowen's disease rather than AK might be involved in the development of HPV-related cuSCC as a precursor.

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Cox2 y Paqudermoperiostosis

The pachydermoperiostosis prostaglandin paradigm 

By Warren R. Heymann, MD
July 10, 2019
Vol. 1, No. 18

Prostaglandins were the rage when I started medical school in 1975; their role in inflammatory dermatoses was considered of paramount importance throughout my residency in the early 1980s. Hours were spent studying the transformation of arachidoinic acid to prostaglandins and leukotrienes, via the respective cyclo-oxygenase and lipoxygenase pathways. In his 1982 Ingram Lecture, Malcom Greaves stated: "The story of prostaglandins (PGs) is in itself a remarkable one, beginning in 1935 with semen and arriving in 1982 in the skin, with a long way to go yet." (1)

This commentary was inspired by a case report with an impressive result, based on understanding molecular mechanisms, leading to treatment modifying of an "old" pathway — the rapid improvement of pachydermoperiostosis (PDP) with etoricoxib (a COX-2 inhibitor). (2)

PDP (aka primary hypertrophic osteoarthropathy or Touraine‐Solente‐Gole syndrome) is a rare genetic disease, with a reported prevalence of 0.16%. Primary clinical features include pachydermia (thickening of skin), clubbing of the digits, and periostosis (new bone formation). In 1935, three French dermatologists, Touraine et al, classified the entity as a familial disorder with three forms: complete (periostosis and pachyderma), incomplete (without pachyderma), and the forme fruste (pachydermia with minimal skeletal changes). Primary PDP usually manifests in adolescence, occurring almost exclusively in males, with a male: female ratio of 7:1. Other features that may accompany PDP are considered minor criteria: cutis verticis gyrata, hyperhidrosis, seborrhea, acne, flushing, arthralgia, joint effusion, and column-like legs. (3,4)

Secondary PDP is far more common that the familial disorder; it occurs as a secondary manifestation of pulmonary or extrapulmonary (cardiac, gastrointestinal, hepatobiliary, hematological) chronic diseases and malignancies. Hypertrophic osteoarthropathy associated with pulmonary pathology is also known as hypertrophic pulmonary osteoarthropathy (HPOA). The common age of presentation is 55 to 75 years, without racial or gender predominance. Ninety percent of reported HPOA is associated with malignancy. Non-small cell lung cancer is the most common cause of secondary hypertrophic osteoarthropathy. (5)

Primary PDP is inherited as an autosomal recessive disorder, although autosomal dominant transmission has been described in some families with incomplete penetrance. Recent molecular studies identified a mutation in the hydroxyl‐prostaglandin dehydrogenase (HPGD) gene, encoding a prostaglandin E2 (PGE2) catabolizing enzyme. Another mutation has been found in the SLCO2A1 gene (solute carrier organic anion transporter family member 2A1), which encodes a prostaglandin transporter responsible for uptake of PGE2. Mutations in these two genes result in higher levels of PGE2 when compared to healthy controls. (6) Pachydermia severity and the associated histological changes are correlated with serum PGE2 levels. Elevated PGE2 levels are hypothesized to induce cytokine-mediated tissue remodeling and vascular stimulation, by platelet-derived growth factor (PDGF) and vascular endothelial growth factor, respectively. (2,4) 

Despite stabilizing over time, PDP's effect on quality of life may be profound. Unfortunately, no specific therapies for primary PDP exist. Therapeutic options have included NSAIDs, systemic corticosteroids, colchicine, isotretinoin, botulinum toxin, and plastic surgery. (3,7) The main thrust of managing secondary PDP is treating the primary disease process, such as associated malignancies, which, if successful, improve the appearance of PDP. (5)

As stated earlier, the impetus for this commentary was the report of dramatic improvement of PDP in a 26-year-old Chinese man due to a mutation in the SLCO2A1 gene, treated with the COX-2 inhibitor etoricoxib. Improvement started within a week of treatment. (2) This drug is not available in the United States, however, should I see such a patient, or even with a forme fruste of the disorder such as cutis verticis gyrata, I will strongly consider the use of celecoxib. Alesandrella et al reported the case of a 17-year-old man with PDP due to a novel mutation of the SLCO2A1 gene, who demonstrated striking improvement with hydroxychloroquine over 18 months. (6) Hydorxychloroquine has only a mild inhibitory effect on cyclo-oxygenases (8); presumably other anti-inflammatory mechanisms may be responsible for its efficacy. 

Prostaglandins may no longer be in vogue, but their biologic effects are vital nevertheless. Although two case reports may not change the therapeutic paradigm for primary or secondary PDP, they open new vistas for therapy and research for these significant disorders.

Point to remember: Inhibiting prostaglandin E2 (PGE2), either by COX-2 inhibition, or possibly by hydroxychloroquine, may be a valuable therapeutic option for patients with pachydermoperiostosis. 

---

 

Our expert's viewpoint

By Ian Coulson, BSc, MBBS, FRCP

Being of the same vintage as Dr. Heymann, prostaglandins and leukotrienes were the source of considerable research. Indeed, I recall having an intradermal infusion of 5 HETE and a skin biopsy taken 24 hours later — the histologic picture showed features of acute psoriasis. The research was headed by Malcolm Greaves, one of my first teachers in dermatology, who had the enviable talent for seeing the implications of basic science advances in dermatology. It is nice to see further fruits of basic research to the unusual condition of pachydermoperiostosis. For sufferers developing clubbing, hand hyperhidrosis, swollen wrists, etc., hitherto there has been little to offer by way of therapy. A simple safe therapy as discussed will be welcomed if confirmed by other studies.  


1. Greaves MW. Prostaglandins and dermatology. The Ingram lecture 1982. J R Coll Physicians Lond 1982; 16: 219-25. 
2. Li Z, Yang Q, Yang Y, Wang D, Wang S. Successful treatment of pachydermoperiostosis with etoricoxib in a patient with homozygous splice-site mutation in the SLCO2A1 gene. Br J Dermatol 2019; 180: 682-684. 
3. Salah BI, Husari KI, Hassouneh A, Al-Ali Z, Rawashdeh B. Complete primary pachydermoperisotosis: A case report from Jordan and review of the literature. Clin Case Rep 2019; 7: 346-352. 
4. Joshi A, Nepal G, Shing YK, Panthi HP, Baral S. Pachydermoperiostosis (Touraine-Solente-Gole syndrome): A case report. J Med Case Rep 2019; 13: 39. 
5. Chakraborty RK, Sharma S. Secondary hypertrophic osteoarthropathy. StatPearls [Internet]. Treasure Island (FL); StatPearls Publishing 2019-2019 Jan 1. 
6. Alessandrella A, Casa RD, Alessio M, Prieto JP, et al. A novel homozygous mutation in the SLCO2A1 gene causing pachydermoperiostosis: Efficacy of hydroxychloroquine treatment. Am J Med Genet A; 2018: 176: 1253-1257.
7. Taichao D, Fuling L, Hengguang Z. Comprehensive surgical strategies for the management of pachydermoperiostosis. Facial Plast Surg 2018; 34: 330-333
8. Ben-Chetrit E, Fischel R, Hinz B, Levy M. The effects of colchicine and hydroxychloroquine on the cyclo-oxygenases COX-1 and COX-2. Rheum Int 2005; 25: 332-335. 

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Fototerapia Vitiligo

As all patients were of skin type IV and V, the minimal erythema dose (MED) was not calculated and the initial dose of 150 mJ/cm ² was started and the treatment was administered 2 times/week on nonconsecutive days. The irradiation dose was increased by 20% for each subsequent visit till the optimal dose was achieved to obtain minimal erythema in the lesions. If symptomatic erythema, burning pain or blistering developed, the irradiation dose was decreased by 20%. During treatment, the affected parts were only exposed, and the genitalia and other uninvolved areas were protected. Similarly, the eyes were protected by UV-blocking goggles. If significant depigmentation was present on the eyelids and if patients or parents insisted on treating these areas, the patients were advised to keep their eyes closed during treatment. All the patients were asked to use sunscreens during daytime.

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Benjamin Hidalgo-Matlock

Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054

Momentum Escazu: 2101-9574

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Natural

Spending At Least Two Hours Weekly In Natural Environment May Lead To Better Physical Health, Psychological Well-Being, Research Suggests

The Washington Post (7/5, Searing) reported, "New research finds that people who spend at least two hours a week in a natural environment – like parks, beaches, woodlands or urban green spaces – are more likely to have better physical health and psychological well-being than those who do not venture into the great outdoors." The findings, based on "data from a nationally representative sample of 19,806 British adults," were published in Scientific Reports and "found 59 percent improved odds for overall good health and 23 percent better odds of psychological well-being." The experts "expressed hope that their findings might inspire health guidelines calling for 120 minutes a week of nature exposure, similar to the Physical Activity Guidelines, put out by the U.S. Department of Health and Human Services, that call for 150 minutes a week of moderate physical activity."

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Benjamin Hidalgo-Matlock

Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054

Momentum Escazu: 2101-9574

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Clascoterone Is a Novel Androgen Receptor Antagonist That Inhibits Production of Lipids and Inflammatory Cytokines From Sebocytes in Vitro

Journal of Drugs in Dermatology

TAKE-HOME MESSAGE

• In this in vitro study, cortexolone 17α-propionate (clascoterone) bound to androgen receptors with high affinity, antagonized testosterone-stimulated transcription activity, and inhibited DHT-induced lipid synthesis and inflammatory cytokine pathways in human sebocytes.

• Clascoterone demonstrated strong potential for becoming the first topical anti-androgen in the treatment of acne. Large phase III clinical trials, which are ongoing, may determine its potency in acne therapy.

– Caroline K. Crabtree, MD

Written by

 

 

Jerry K. L. Tan MD, FRCPC

The Advent of a Novel, Topical Acne Therapy Based on Sebocyte Inhibition, Clascoterone

Of the primary pathogenic factors in acne, namely follicular hyperkeratinization, inflammation, Cutibacterium acnes proliferation, and sebum hyperexcretion, topical therapies are available for all except the latter. This paper describes the in vitro effect of an androgen receptor antagonist, clascoterone, in inhibiting testosterone-stimulated production of pro-inflammatory mediators and lipids from human sebocytes.

Although the mechanism of action of drugs in dermatology is important, of primary relevance to patients and clinicians is the question—can it work and if so, how well? The recent history of topical acne drug development has been punctuated by excitement and innovation but fraught with challenges and failure in pivotal trials (eg, olumacostat glasaretil). This has not been the case for clascoterone. Can it work? Two phase III randomized controlled trials of clascoterone 1% cream (Winlevi® 1% cream, Cassiopea) vs vehicle involving just over 1400 patients with moderate to severe acne were completed in 2018. Both trials achieved primary and secondary endpoints of superiority vs vehicle in investigator global assessments (achievement of clear or almost clear and 2 grade reduction) and in reduction of inflammatory and comedonal acne lesion counts at 12 weeks of therapy, with tolerability and safety similar to vehicle.

The advent of a novel, topical agent based on sebocyte inhibition, a mechanism of action not previously addressed by topical acne medications, is finally here. How well does it work? The answer lays in future comparative clinical trials and clinical experience.

Abstract 

Cortexolone 17α-propionate (clascoterone) is a novel topical androgen antagonist that is being analyzed for its ability to treat acne. The pathogenesis of acne is attributed to multiple factors, including altered sebum production, inflammatory processes, dysregulation of the hormone microenvironment, and the proliferation of the skin commensal bacteria, Propionibacterium acnes (P. acnes). Androgens induce the proliferation and differentiation of sebocytes, (cells that comprise the sebaceous gland), help regulate the synthesis of the lipids that are incorporated into sebum and stimulate the production of cytokines that are found in inflammatory acne lesions. Several studies have established that clascoterone is a potent antiandrogen that is well tolerated and has selective topical activity. Its potency as an acne therapeutic is currently being analyzed in a large phase 3 clinical trial. The study described herein elucidates for the first time the mechanism of action of clascoterone. Clascoterone was found to bind the androgen receptor (AR) with high affinity in vitro, inhibit AR-regulated transcription in a reporter cell line, and antagonize androgen-regulated lipid and inflammatory cytokine production in a dose-dependent manner in human primary sebocytes. In particular, when compared to another AR antagonist, spironolactone, clascoterone was significantly better at inhibiting inflammatory cytokine synthesis from sebocytes. Therefore, clascoterone may be an excellent candidate to be the first topical antiandrogen to treat acne.

Journal of Drugs in Dermatology

Cortexolone 17α-Propionate (Clascoterone) Is a Novel Androgen Receptor Antagonist That Inhibits Production of Lipids and Inflammatory Cytokines From Sebocytes In Vitro

J Drugs Dermatol 2019 May 01;18(5)412-418, C Rosette, FJ Agan, A Mazzetti, L Moro, M Gerloni 

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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10 Medical Myths We Should Stop Believing. Doctors, Too. - The New York Times

https://www.nytimes.com/2019/07/01/health/medical-myths-doctors.html?nl=todaysheadlines&emc=edit_th_190702?campaign_id=2&instance_id=10617&segment_id=14842&user_id=0e2e6314f0e5091afc3e332d4b43fd3d&regi_id=550594430702

10 Medical Myths We Should Stop Believing. Doctors, Too.

By Gina Kolata

July 1, 2019

You might assume that standard medical advice was supported by mounds of scientific research. But researchers recently discovered that nearly 400 routine practices were flatly contradicted by studies published in leading journals.

Of more than 3,000 studies published from 2003 through 2017 in JAMA and the Lancet, and from 2011 through 2017 in the New England Journal of Medicine, more than one of 10 amounted to a "medical reversal": a conclusion opposite of what had been conventional wisdom among doctors.

"You come away with a sense of humility," said Dr. Vinay Prasad of Oregon Health and Science University, who conceived of the study. "Very smart and well-intentioned people came to practice these things for many, many years. But they were wrong."

Some of those ideas have been firmly dislodged, but not all. Now Dr. Prasad and his colleagues are trying to learn how widespread are discredited practices and ideas.

Here are 10 findings that contradict what were once widely held theories.

• Peanut allergies occur whether or not a child is exposed to peanuts before age 3.

Pediatricians have counseled parents to keep babies away from peanuts for the first three years of life. As it turns out, children exposed to peanuts before they were even 1 year old have no greater risk of peanut allergies.

• Fish oil does not reduce the risk of heart disease.

At one point, the notion that fish fats prevented heart trouble did seem logical. People whose diets contain a lot of fatty fish seem to have a lower incidence of heart disease. Fatty fish contains omega-3 fatty acids. Omega-3 supplements lower levels of triglycerides, and high levels of triglycerides are linked to an increased risk of heart disease. Not to mention that omega-3 fatty acids seem to reduce inflammation, a key feature of heart attacks.

But in a trial involving 12,500 people at risk for heart trouble, daily omega-3 supplements did not protect against heart disease.

• A lifelike doll carried around by teenage girls will not deter pregnancies.

These dolls wail and need to be "changed" and "cuddled." The idea was that girls would learn how much work was involved in caring for an infant. But a randomized study found that girls who were told to carry around "infant simulators" actually were slightly more likely to become pregnant than girls who did not get the dolls.

• Ginkgo biloba does not protect against memory loss and dementia.

The supplement, made from the leaves of ginkgo trees, was widely used in ancient Chinese medicine and still is promoted as a way to preserve memory. A large federal study, published in 2008, definitively showed the supplement is useless for this purpose. Yet ginkgo still pulls in $249 million in sales. Did people just not get the message?

• To treat emergency room patients in acute pain, a single dose of oral opioids is no better than drugs like aspirin and ibuprofen.

Yes, opioids are powerful drugs. But a clinical trial showed that much safer alternatives relieve pain just as well among emergency room patients.

• Testosterone treatment does not help older men retain their memory.

Some men have low levels of testosterone and memory problems, and early studies had hinted that middle-aged men with higher testosterone levels seemed to have better preserved tissue in some parts of their brains. Older men with higher testosterone levels also seemed to do better on tests of mental functioning.

But a rigorous clinical trial showed that testosterone was no better than a sugar pill in helping older men avoid memory loss.

• To protect against asthma attacks, it won't help to keep your house free of dust mites, mice and cockroaches.

The advice from leading medical groups has been to rid your home of these pests if you or your child has asthma. The theory was that allergic reactions to them can trigger asthma attacks. But intensive pest management in homes with children sensitized to mouse allergens did nothing to reduce the frequency of their asthma attacks, researchers reported in 2017.

• Step counters and calorie trackers do not help you lose weight.

In fact, the reverse is true. Among 470 dieters followed for two years, those who wore devices tracking the steps they took and calories they burned actually lost less weight than those who just followed standard advice.

• Torn knee meniscus? Try physical therapy first, surgery later.

An estimated 460,000 patients in the United States get surgery each year to fix knee cartilage that tears, often because of osteoarthritis. The tear is painful, and many patients fear that if it is not surgically treated, the pain will linger.

But when patients with a torn meniscus and moderate arthritis were randomized to six months of physical therapy or surgery, both groups improved, and to the same extent.

• If a pregnant woman's water breaks prematurely, the baby does not have to be delivered immediately.

Sometimes, a few weeks before a woman's due date, the membrane surrounding her fetus ruptures and amniotic fluid spills out. Obstetricians worried that bacteria could invade what had been a sterile environment around the fetus, causing infection. Better to deliver the baby immediately, doctors thought.

But a clinical trial found that if obstetricians carefully monitor the fetus while waiting for labor to begin naturally, the fetus is at no greater risk for infection. And newborns left to gestate were healthier, with less respiratory distress and a lower risk of death, than those who were delivered immediately after a break.

An earlier version of this article misstated the annual sales of ginkgo. It is $249 million not billion.

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Benjamin Hidalgo-Matlock
Skin Care Physicians of Costa Rica

Clinica Victoria en San Pedro: 4000-1054
Momentum Escazu: 2101-9574

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