Ajay Kailas

Suggestions for Increasing Diversity in Clinical Trials

Suggestions for Increasing Diversity in Clinical Trials To the Editor The article by Charrow et al1 discusses the gap in proportional racial representation in clinical trials. We applaud the authors for bringing this topic to the forefront. One shortcoming of the article, however, is that it does not discuss measures for correcting this gap. Therefore, the purpose of this letter is to provide suggestions derived from clinical trial literature to improve minority participation. One of the most substantial barriers in recruiting minority participants in clinical trials is lack of education regarding clinical trials.2 Hence, educating minority communities regarding clinical trials through in-person or virtual information sessions may prove useful. Prior to the initiation of a specific clinical trial, community information sessions may be scheduled for potentially interested participants so that they can learn about trials in general as well as the specific trial to be conducted. Minority groups often harbor a lack of trust rooted in historical mistreatment in trials, and it is critical to overcome this issue to engage participants. This type of forum will also allow community members to meet the research team they could potentially be working with and begin developing a relationship of mutual respect and trust. Lack of awareness by various racial groups that clinical trials are being conducted is another reason for low participation.2 Therefore, it is critical to inform minority participants that a trial is being conducted by going into their communities, including black and Hispanic churches, Hindu and Buddhist temples, and community cultural events. Advertising in local black and Hispanic newspapers and on Facebook groups will also likely yield diverse participants. Social media may be especially helpful for clinical trials that focus on rarer diseases; there are large numbers of Facebook groups with active members who welcome such posts. The third major issue discussed in the literature inhibiting minority enrollment relates to language barriers.3 This may be particularly prevalent among Hispanic populations who may not speak or read English at a level required to understand an informed consent. Diverse and bilingual medical staff and researchers who speak Spanish can ameliorate this problem. Translation of all trial materials is another mechanism for including diverse populations. For studies being conducted in academic centers, medical students and residents who speak Spanish may be a particularly good resource. We thank Charrow et al1 for furthering the dialogue regarding this important topic and hope that our recommendations will assist researchers in reducing the numerous barriers to minority representation in clinical trials.

Crisaborole: A new and effective nonsteroidal topical drug for atopic dermatitis

Atopic dermatitis (AD) is a chronic, intermittent, and pruritic disease that commonly begins in childhood. The disease is disabling primarily because of excessive pruritus. Topic corticosteroids are the mainstay therapy for this condition, with topical calcineurin inhibitors used as second line. Corticosteroids however, tend to result in negative side effects when used long-term such as skin atrophy, telangiectasias, and striae formation. Topical calcineurin inhibitors (such as tacrolimus or picrolimus) are often associated with burning or stinging upon application. More seriously, they carry a black box warning for lymphoma. A new nonsteroidal drug called Crisaborole (Eucrisa) has been investigated for potential long-term use in AD. It was FDA approved in December 2016. Crisaborole contains a boron atom, which allows for better skin penetration. It works by blocking PDE4, a key regulator in the inflammatory cytokine cascade that degrades cAMP. The new drug has been tested in two double-blind, vehicle controlled randomized clinical trials in which a 2% topical ointment was used twice daily for 28 days in patients aged 2 and older with moderate to severe AD. The results were promising, with patients achieving Investigator’s Static Global Assessment score success (clear/almost clear with secondgrade improvement; AD-301: 32.8 vs. 25.4%, p5 .038; AD-302: 31.4 vs. 18.0%, p< .001), and with more patients reporting clear/almost clear results (51.7 vs. 40.6%, p5 .005; 48.5 vs. 29.7%, p< .001) for each of the two trials respectively (Paller et al., 2016). Of note, no patients reported skin atrophy or telangiectasias. Side effects of the medication were rare and were limited primarily to application site pain (occurred in 4.4% of patients compared to 20– 58% of tacrolimus). Crisaborole is an exciting new nonsteroidal drug that offers a better safety profile, while also being effective. CONFLICT OF INTEREST

Gaps in the understanding and treatment of skin cancer in people of color

People of color are at significantly higher risk in mortality from skin cancers, such as melanoma, than Caucasians. Around 4,500,000 people of color are affected by skin cancer The five-year survival rates from melanoma are 81.1% for Hispanics, 80.2% for Asians, 72.2% for African- Americans, and 89.6% for Caucasians. For this reason, it is important to ensure the scientific literature reflects the most up to date recommendations and treatment for blacks regarding skin cancer. Therefore the authors conducted a “gap analysis” on the current treatment of skin cancer in people of color. Three major areas of deficiency were identified. The first major gap identified is the lack of a clear definition of people of color in the literature. The vast majority of current studies utilize the terms Hispanic, Asian, and African-American as if they were all-inclusive, homogenous groups. The second gap identified is the widespread false assumption among dermatologists that people of color do not participate in tanning activities or at risk for UV induced skin cancer. The third gap identified is the false belief among people of color that darker pigmentation confers a “total immunity” against skin cancer. Hopefully raising awareness for these issues will eventually lead to appropriate research and solutions from the medical community as well as the population at risk to lead to the closure of these gaps.

Cutaneous intravascular CD30+ T-cell pseudolymphoma occurring in a regressing keratoacanthoma

Cutaneous intravascular CD30+ pseudolymphoma is an uncommon incidental finding that may mimic intravascular or angiotropic lymphoma. We describe a 78‐year‐old female with a traumatized regressing keratoacanthoma on her left cheek. A shave biopsy revealed intravascular staining of atypical lymphocytes positive for CD45, CD3 and CD30. Clinical exam revealed no other evidence of lymphoma, the patient denied constitutional symptoms, and routine blood work was normal. The patient is healthy and doing well 28 months after her first visit. CD30+ pseudolymphoma should be distinguished from malignant intravascular lymphoproliferative disorders.

Dermatology in Epic Poetry—From Beowulf to The Odyssey

Epic poems have captured the imaginations of readers, listeners, and artists alike for millennia. Michelangelo painted part of the Sistine Chapel after being inspired by Dante’s Divine Comedy. Shakespeare’s 1602 play, Troilus and Cressida, is based on The Iliad, an ancient Greek epic poem attributed to Homer. All told, epic poems are captivating tales full of wonder and adventure. Particularly, they have often integrated dermatology in their unique plots. Beowulf is an Old English poem (written circa AD 700-1000) that tells of the powerful Geat hero Beowulf, who visits the mead hall, Heorot, to kill the evil monster Grendel. Grendel, bothered by the sounds of joy, has gruesomely slaughtered Heorot’s inhabitants for years. Owing to his magical gifts, no one has been able to slay him. Grendel not only possesses incredible strength, but his skin is also impenetrable to any blade: “Every nail, claw-scale, of that heathen brute...was like barbed steel. To pierced him through, no time proofed blade could cut his brutal, blood-caked claw.” Beowulf notably does not use a sword, but rather kills Grendel by directly ripping his arm off, causing him to bleed to death. In the 13th century German epic poem Das Nibelungenlied (The Song of the Nibelungs), the skin of a main character is a weakness rather than a strength. In the beginning of the story, the knight Siegfried is said to have slaughtered a dragon and bathed in his blood—rendering him invulnerable to weaponry. However, a leaf from a linden tree fell between his shoulders during this bath, leaving that area untouched with blood. His wife, Kriemhild, mentions, “There one might stab him, and thence is my care and dole,” indicating that this is his only weakness (similar to Achilles’ heel). Unfortunately, Siegfried is later murdered by Hagen, who spears the unsuspecting knight while he is drinking from a brook. His death inspires Kriemhild’s revenge, which is the focus of the second half of Das Nibelungenlied. The Odyssey, a Greek epic poem by Homer, details the legendary return of Odysseus to his home of Ithaca after the Trojan war. Arriving after 20 years, he discovers that multiple suitors are courting his wife, Penelope, presuming he is dead. Odysseus is then transformed by Athena (the goddess of war) into an old man as a disguise. However, his housekeeper, Eurycleia, identifies him because of a hunting scar on his leg: “She immediately recognized the scar; which once a boar inflicted upon him.” This discovery demonstrates Eurycleia’s loyalty and allows the Odysseus and Penelope to reunite. Together, they plot to kill the suitors and eventually restore peace to Odysseus’ kingdom. Ultimately, epic poems are full of fantastic details and magical characters. Many tales involve the skin, demonstrating dermatology’s unique significance in literature. Hopefully, epic poetry will continue inspiring many more for ages to come.

Why Outcome Measures in Dermatology Are Becoming Patient Centric

Purpose of ReviewMany “validated” treatment outcome assessments in clinical trials fail to include outcomes important to patients. This review will focus on recent efforts to revise and make patient-centric clinical trial outcomes used in psoriasis, acne vulgaris, atopic dermatitis, and hidradenitis suppurativa.Recent FindingsOver recent years, international coalitions have been formed to revise the investigator-oriented “validated” measures (e.g., PASI, IGA) in order to incorporate outcomes important to patients These not only include quality of life (QoL) assessments but also the anatomic location, physical discomfort, and appearance. This review discusses work underway to include patients in formatting revised outcome assessments.SummaryHistorically, outcome measures have been developed by clinicians and pharmaceutical companies for use in clinical trials. Nonetheless, a movement is underway supported by regulatory agencies, government officials, and patient advocacy groups to include patients in the process of redesigning clinical trial outcome measures.