Topical Conversations

For Rare Disease Day on February 29, Topical Conversations will be exploring some of the rare diseases seen in dermatology. In this installment, Charlie Dunn, MD, speaks with Brett Kopelan, Executive Director of debra of America, a nonprofit organization dedicated to improving the lives of those impacted by epidermolysis bullosa (EB) and supporting the clinicians who treat this condition. Watch Part 1 to hear Dr Todd Schlesinger discuss SCLE and dermatomyositis.Watch Part 2 to hear Dr Naiem Issa discuss tuberous sclerosis complex and a helpful treatment tip.Watch Part 3 to hear Dr James Del Rosso discuss new and emerging therapies for congenital ichthyoses, EB, and facial angiofibromas.About debra of America Founded in 1980, debra of America emerged from the dire need for institutional and public knowledge about EB. debra, which now comprises over 52 autonomous branches worldwide, works to improve the quality of life for all patients, families, caregivers, and clinicians who manage EB through programs and services, educational resources, and research funding. Resources for patients and clinicians debra of America's mission is to enhance the lives of those living with EB through patient services, industry partnerships, and support for clinicians and researchers engaged in innovative research. Recognizing the challenges faced by medical professionals unfamiliar with treating rare diseases, debra offers programs such as the EN Nurse Educator Program. The EB Nurse Educator serves as a trusted source of accurate information for those living with EB, their families, and the medical community. debra estimates that 20% of the calls the EB Nurse Educator receives come from medical professionals seeking guidance on how to care for patients with EB and resources to support them. The debra website also boasts a robust How To section, which provides resources to guide patients and caregivers in making informed decisions surrounding proper EB care. These guides cover topics such as caring for wounds and blisters, caring for newborns, preparing baths, recognizing infection, choosing products, and more. Physician resources and multidisciplinary approaches In addition to patient-focused resources, debra also collaborates with health care professionals to cowrite clinical best practice guidelines that address anesthesia, pain management, GI issues, social and emotional well-being, and more. The complex nature of EB often necessitates a multidisciplinary approach to care, involving dermatology, gastroenterology, physical therapy, occupational therapy, pain management, psychology, and cardiology, and debra curates services for all aspects of care. Emerging therapeutics Exciting developments in EB therapeutics include the recent approval of the first redosable gene therapy and a topical wound healing agent. Anticipated approval for a second gene therapy, an ex-vivo approach, in May 2024 adds to the optimism. debra of America plays a crucial role in bringing the patient voice into drug development for EB, potentially easing the regulatory pathway and reducing the time it takes for new therapies to get to market. An appeal to the dermatology community EB is traditionally thought of as a pediatric condition within the dermatology community. As emerging therapies extend the lifespan of patients with EB, debra urges dermatology professionals to pay increased attention to adult care and treatment. With only one adult multidisciplinary center in the country, there is a need for the dermatology community to embrace the challenges associated with transitioning from pediatric to adult EB care. Interested in getting involved with debra? Check out opportunities here. Download How To guides for patients and clinicians here.Read about the EB Nurse Educator Program here. Download the Skin and Wound Care in Epidermolysis Bullosa Best Practice Guidelines here.

For Rare Disease Day on February 29, Topical Conversations will be exploring some of the rare diseases seen in dermatology. In this installment, James Q Del Rosso, DO, reviews some new and emerging therapies for congenital ichthyoses, epidermolysis bullosa, and facial angiofibromas related to tuberous sclerosis. Watch Part 1 to hear Dr Todd Schlesinger discuss subacute cutaneous lupus erythematosus and dermatomyositis.Watch Part 2 to hear Dr Naiem Issa discuss tuberous sclerosis complex and a breakthrough new treatment.An emerging therapy for congenital ichthyoses Dr Del Rosso begins by reviewing an emerging treatment for congenital ichthyoses, a group of rare genetic keratinization disorders that leads to dry, thickened, and scaling skin and requires lifelong management. The Phase 3 ASCEND study is currently underway and focusing on 2 moderate-to-severe subtypes, lamellar ichthyosis and X-linked ichthyosis, that affect about 80,000 individuals in the United States. The ASCEND study is investigating the efficacy and safety of a topical isotretinoin, TMB-001, in a patented special delivery system. A topical formulation of isotretinoin may help reduce systemic absorption, potentially allowing for chronic use over larger areas of the body and shows promise for those affected by congenital ichthyoses. A new approval for epidermolysis bullosa Dr Del Rosso also lauds a newly approved therapy for epidermolysis bullosa, a topical gel birch triterpenes for the treatment of partial thickness wounds in patients 6 months and older with junctional epidermolysis bullosa and dystrophic epidermolysis bullosa. As the first FDA-approved treatment for wounds associated with junctional epidermolysis bullosa, topical gel birch triterpenes is a promising development for patients facing daily challenges from open wounds, one of the most visible and difficult-to-manage symptoms of epidermolysis bullosa. A topical option for facial angiofibromas Another recent approval making progress for rare diseases in dermatology is a topical sirolimus gel for the treatment of facial angiofibromas associated with tuberous sclerosis. By inhibiting the mTOR pathway that leads to cellular proliferation, this therapy, approved for 6 years of age and older, is a significant step forward in managing cutaneous manifestations of tuberous sclerosis.

For Rare Disease Day on February 29, Topical Conversations will be exploring some of the rare diseases seen in dermatology. In this installment, Naiem Issa, MD, PhD, gives his perspective on tuberous sclerosis complex (TSC) along with a helpful treatment tip. Watch Part 1 to hear Dr Todd Schlesinger discuss subacute cutaneous lupus erythematosus and dermatomyositis.Understanding tuberous sclerosis complex Tuberous sclerosis complex (TSC) is a rare genetic disorder resulting from mutations in the TSC1 and TSC2 genes. It follows an autosomal dominant pattern and affects approximately 50,000 individuals in the United States. TSC is difficult to treat and requires a multidisciplinary, multimodal treatment paradigm. TSC presents with multiple comorbidities, including central nervous system abnormalities, brain tumors causing seizures or developmental delays, angiomyolipoma and kidney cysts, cardiac rhabdomyelomas, pulmonary cysts, and lymphangioleiomyomatosis. Cutaneous manifestations include periungual fibromas, typically developing around the feet, and facial angiofibromas. Dermatologists play a crucial role in addressing patients' concerns related to facial angiofibromas, one of the most visible manifestations of TSC. Challenges with traditional treatments Facial angiofibromas are often a primary concern for patients with TSC, as they can present with hundreds of lesions. Traditionally, treatment options have been limited to destructive modalities such as curettage, laser therapy, and excisions, all of which come with side effects. Role of mTOR signaling in TSC The pathogenesis of TSC involves the dysregulation of the mammalian target of rapamycin (mTOR) signaling pathway. Inhibition of mTOR has shown promise in addressing both cutaneous and systemic effects of TSC. Oral sirolimus has been a standard therapeutic approach, but recent advancements have introduced a topical sirolimus 0.2% gel approved for ages 6 and above. Topical sirolimus gel for facial angiofibromas The approval of topical sirolimus gel is a significant advancement in TSC treatment. As a nondestructive alternative that inhibits mTOR locally, it provides a targeted treatment that minimizes side effects associated with systemic administration. Dr Issa encourages dermatologists to consider incorporating topical sirolimus gel into their treatment armamentarium for patients with TSC who present with multiple facial angiofibromas. This novel approach not only enhances the management of the cutaneous manifestations of TSC but also aligns with a patient-centered approach by minimizing the impact of side effects associated with traditional therapies.

For Rare Disease Day on February 29, Topical Conversations will be exploring some of the rare diseases seen in dermatology. In this installment, Todd Schlesinger, MD, FAAD, FASMS, gives his perspective on subacute cutaneous lupus erythematosus (SCLE) and dermatomyositis. Watch Part 2 to hear Dr Naiem Issa discuss tuberous sclerosis complex and a breakthrough new treatment.Subacute cutaneous lupus erythematosus SCLE is a condition linked to systemic lupus erythematosus in 50% of patients; it may also be associated with Sjögren’s syndrome. SCLE manifests as a small, red, scaly papular eruption in sun-exposed areas, progressing to a psoriasiform or annular lesion. This photosensitive dermatosis is nonscarring and nonatrophic, with lesions healing without scarring but potentially leaving some dyspigmentation. Commonly affected regions include the shoulders, forearms, neck, and upper torso. Around 50% of patients with SCLE patients experience joint involvement, with often symmetrical arthralgias usually affecting small joints like wrists and hands. Dr Schlesinger notes that SCLE is a notably challenging condition in dermatology but expresses hope for new treatments in the pipeline, potentially ones that leverage existing medications used for psoriasis and atopic dermatitis. Dermatomyositis Dermatomyositis is a rare, idiopathic inflammatory disorder primarily affecting the skin and muscles but sometimes also affecting the joints, esophagus, lungs, and heart. It falls within the category of myositis, a rare group of diseases characterized by inflamed muscles, and poses challenges for dermatologists due to its complexity in both diagnosis and treatment. The condition is characterized by distinctive skin findings, including a heliotrope rash around the eyes, Gottron papules over the joints, and facial erythema over the cheeks and nasal bridge. Muscular involvement often leads to weakness, particularly in the proximal muscles. Treating patients with dermatomyositis and related myositic disorders poses diagnostic and therapeutic challenges, and Dr Schlesinger comments that this condition, along with the broader category of myositic disorders, has not received sufficient attention. He looks forward to innovation in this area to improve approaches to diagnosis and treatment. Overlapping pathways Dr Schlesinger also emphasizes the overlapping inflammatory pathways that SCLE and dermatomyositis share with the more common dermatologic conditions, especially alopecia areata, atopic dermatitis, and psoriasis. With a focus on research, innovation, and collaborative efforts, dermatologists can work to address the diagnostic and therapeutic challenges associated with these rare diseases in dermatology.

In recognition of World Leprosy, join Charlie Dunn, MD, for this episode of Topical Conversations to hear a dermatologist’s overview of leprosy, shedding light on the progress made, emerging insights, and the vital role dermatologists play in recognizing, treating, and caring for patients affected by this rare disease. Reviewing the basics Leprosy, also known as Hansen's disease, is caused by the slow-growing mycobacterium leprae complex, which tends to involve the skin and peripheral nerves. The global health perspective Despite tremendous advancements in recognition and treatment, leprosy remains a significant global health concern. Annually, approximately 200,000 cases are diagnosed worldwide. The United States, while experiencing relatively low case counts, has seen a notable geographical incidence shift, particularly in the southeast. In 2020, more than one-fifth of cases were identified in Florida, with 80% of those cases occurring in eastern Florida. The reasons behind the increase in geographic incidences are not yet identified but may be related to a shift in disease transmission. Disease transmission Due to the slow-growing nature of the bacteria, transmission is not fully understood. Transmission of leprosy is historically linked to genetic susceptibility and prolonged exposure to someone with untreated disease via respiratory droplets. However, there are an increasing number of cases in the US where close contact cannot be established. In these cases, transmission is thought to occur either through prolonged travel within countries with high rates of the disease or through zoonotic exposure. Zoonotic exposure is thought to be key to the increased prevalence of leprosy in the southeastern United States particularly via nine-banded armadillos, which are known reservoirs for mycobacterium leprae strains known to infect humans. Clinical presentation Leprosy manifests in diverse ways, largely depending on the bacteria burden and the infected person’s immune response. Clinical manifestations can be considered across 2 ends of a spectrum. One end is tuberculoid leprosy, where there is a robust immune response to the disease. These patients tend to have a small number of well-demarcated patches or plaques that are lightly pigmented, may be red or rust-colored in the center, and have a degree of sensation abnormalities. Patients may also present with poor hair growth or abnormal sweating. On the other end is lepromatous leprosy, where there is no apparent resistance to mycobacterium leprae. Patients present with poorly demarcated, nodular lesions on all parts of the body. With nerve involvement, patients may present with numbness or tingling of the hands and feet, tender, enlarged peripheral nerves, and lumps or swelling of the earlobes or face. If these nerve findings progress, they can lead to hand and foot weakness, facial paralysis, loss of eyelashes or eyebrows, and leonine facies. Diagnosing leprosy Diagnosis is established via a skin biopsy, ideally from the leading edge of a lesion that demonstrates the bacterial within a cutaneous nerve. In tuberculoid, or paucibacillary, leprosy, this can be challenging; multiple biopsies may be needed, and diagnosis may need to be inferred from clinical or histopathologic clues. One vital aspect of diagnosis to remember is that leprosy is a reportable condition at both the state and federal level. The National Hansen’s Disease Program (NHDP), once notified, provides telemedicine visits and medications for patients and professional consultation for clinicians, all at no cost. Treating leprosyContrary to popular misconceptions, leprosy is highly treatable, with patients becoming noninfectious within days after starting antibiotics. Monthly directly observed therapy (DOT) is recommended by the NHDP, consisting of treatment with rifampin, moxifloxacin or ofloxacin, and minocycline. A key unique component to treating leprosy is screening all patients, at the time of diagnosis, regularly during treatment, and after treatment, for immunologic reactions. These reactions can result in severe nerve injury if not treated promptly. Addressing the stigma Leprosy continues to carry societal stigma. Dermatologists play a crucial role in dispelling misconceptions, advocating against stigma, and promoting awareness at both individual and community levels. Key points Increasing rates of leprosy have presented in the southeast US, particularly Florida, in recent years Transmission is linked to close contact and zoonotic exposure Diagnosis can be made via biopsy or inferred from clinical or histopathologic clues Leprosy must be reported at the state and federal levelsDirectly observed therapy with rifampin, moxifloxacin or ofloxacin, and minocycline is recommended Patients should be screened on an ongoing basis for immunologic reactions Dermatologists play a crucial role in dispelling stigmas around leprosy