Growth Factors to Enhance Nerve Regeneration: Approaching Clinical Translation.

Following nerve injury, growth factors (GFs) are transiently upregulated in injured neurons, proliferating Schwann cells, and denervated muscle and skin. They act on these same cells and tissues to promote nerve regeneration and end-organ reinnervation. Consequently, much attention has been focused on developing GF-based therapeutics. A major barrier to clinical translation of GFs is their short half-life. To provide sustained GF treatment to the affected nerve, muscle, and skin in a safe and practical manner, engineered drug delivery systems are needed. This review highlights recent advancements in GF-based therapeutics and discusses the remaining hurdles for clinical translation.

The diagnostic difficulties of juvenile vulvar pemphigoid.

Mucous membrane pemphigoid is a rare autoimmune disease affecting mucosal surfaces. Pediatric cases are exceptionally rare, one subtype being vulvar pemphigoid. Juvenile vulvar pemphigoid can be challenging to diagnose due to its rarity and subtle initial symptoms. We present a case of an 8-year-old girl successfully diagnosed early in the disease course via histopathology, and immunofluorescence. Detecting MMP can be complex due to variations in epitope binding typically not included in commercial ELISA assays, necessitating comprehensive workup. Missed diagnosis may lead to progression to systemic involvement with severe consequences; thus, timely diagnosis and treatment are crucial.

Dupilumab-induced psoriasiform dermatitis in two pediatric cardiac transplant patients.

Dupilumab is an interleukin-4 receptor antagonist important in the treatment of refractory atopic dermatitis (AD), particularly among pediatric patients. Two boys with a history of AD and cardiac transplant who developed psoriasiform dermatitis in response to dupilumab therapy are reported. These patients paradoxically developed an immune-mediated adverse drug reaction despite taking systemic immunosuppressive agents. While the literature suggests possible pathomechanisms for psoriasiform dermatitis despite immunosuppression, further research is necessary to better characterize this unique and unexpected phenomenon.

The Effects of Growth Hormone on Nerve Regeneration and Alloimmunity in Vascularized Composite Allotransplantation.

BACKGROUND: Poor outcomes in functional recovery following upper extremity transplantation are largely due to denervation-induced muscle atrophy that occurs during the prolonged period of nerve regeneration. Growth hormone (GH) has well-established trophic effects on neurons, myocytes, and Schwann cells and represents a promising therapeutic approach to address this challenge. This study sought to confirm the positive effects of GH treatment on nerve regeneration and functional recovery and to evaluate the effects of GH treatment on the immune response in the setting of vascularized composite allotransplantation. METHODS: Rats underwent orthotopic forelimb transplantation across a full MHC-mismatch and received either porcine-derived growth hormone or no treatment (n=18 per group). Functional recovery was measured using electrically-stimulated grip strength testing. Animals were monitored for clinical and subclinical signs of rejection. RESULTS: Neuromuscular junction reinnervation and grip strength were improved in GH-treated animals (p=0.005; p=0.08). No statistically significant differences were seen in muscle atrophy, degree of myelination, axon diameter, and axon counts between groups. The rates of clinical and histological rejection did not significantly differ among groups. CONCLUSIONS: Our findings alleviate concern for increased risk of transplant rejection during GH therapy and therefore support the translation of growth hormone as a therapeutic method to promote improved functional recovery in upper extremity transplantation.

Generalized Pustular Psoriasis: A Review of the Pathophysiology, Clinical Manifestations, Diagnosis, and Treatment.

Generalized pustular psoriasis (GPP) is a rare severe variant of psoriasis that is characterized by the abrupt widespread onset of small pustules accompanied by systemic manifestations of inflammation. It can arise in patients with a history of psoriasis as well as in those without, sometimes due to medication initiation or withdrawal, pregnancy, or infection. Generalized pustular psoriasis is thought to be driven primarily by innate immunity and unrestrained IL-36 cytokine activity. Recent genetic analyses have identified 3 genetic mutations that are associated with GPP-IL36RN, CARD14, and AP1S3-though these mutations only account for a minority of cases. There are many cutaneous pustular diseases that must be ruled out in the evaluation of a patient with suspected GPP, especially acute generalized exanthematous pustulosis (AGEP), and histologic analysis is the cornerstone of diagnosis. Although the quality of evidence to generate treatment recommendations for GPP is limited, management often includes utilization of systemic agents and/or biologics, usually with adjunctive topical treatment. Accumulating evidence suggests that biologic agents, especially infliximab, may be considered as first-line treatment of GPP, especially in severe acute cases, due to their abrupt onset of action and favorable side-effect profiles compared with oral systemic agents.

Effects of Blue Light on the Skin and Its Therapeutic Uses: Photodynamic Therapy and Beyond.

BACKGROUND: Blue light is the most energetic portion of the visible light spectrum. Recent awareness of its ubiquity and potential has led to greater developments in therapeutic uses. OBJECTIVE: Provide up-to-date information on the effects of blue light on the skin, with a focus on the benefits and its place in therapeutic modalities within dermatology. MATERIALS AND METHODS: A systematic review was performed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for articles related to blue light's effect on the skin and therapeutic modalities using blue light. This search resulted in 223 unique results with 60 articles selected for review. RESULTS: Therapeutic modalities using blue light have been proven to be effective as a monotherapy or component of a comprehensive treatment plan for common dermatologic diseases such as actinic keratosis, acne, cutaneous infections, and psoriasis, and early reports support its use in disseminated superficial actinic porokeratosis and actinic cheilitis. CONCLUSION: The benefits and treatment applications of blue light have proven effective in multiple forms and uses. In the correct setting, blue light can be a useful tool to the practicing dermatologist for many common and sometimes refractory skin diseases while remaining low-risk and convenient. Further standardization and monitoring should be pursued to determine the most appropriate use.

A case of annular erythema of infancy accompanied by elevated tryptase.

Annular erythema of infancy (AEI) is characterized by self-limited eruptions of erythematous, annular to polycyclic patches and plaques, the etiology of which is thought to involve a hypersensitivity reaction to an unknown antigen. We present a case of AEI mistaken for systemic mastocytosis due to elevated serum tryptase. We were unable to find prior reports of an association between AEI and elevated tryptase in the literature.

Rare Cutaneous Malignancies in Skin of Color.

BACKGROUND: There is a scarcity of information regarding the clinical characteristics of rare cutaneous malignancies in skin of color that has yet to be comprehensively explored. OBJECTIVE: To review and compile the racial differences in epidemiology, clinical presentation, histology, treatments, and outcomes of 3 rare skin cancers: dermatofibrosarcoma protuberans (DFSP), Merkel cell carcinoma (MCC), and sebaceous carcinoma (SC). METHODS: Several searches with keywords denoting specific skin cancer type and race were conducted on PubMed to complete this narrative review. RESULTS: We analyzed 50 sources that were relevant to the initial objective. CONCLUSION: The literature demonstrates that there are nuances in DFSP, MCC, and SC unique to African Americans, Asians/Pacific Islanders, and Hispanics that may differ significantly from Caucasian counterparts. African Americans consistently suffer from the worst clinical outcomes in all 3 rare cutaneous malignancies reviewed. Greater physician awareness and knowledge of the discussed racial differences is the preliminary step to address these disparities.

Patient Outcomes and Satisfaction After Mohs Micrographic Surgery in Patients With Nonmelanoma Skin Cancer.

BACKGROUND: Quality in medicine is increasingly being measured through patient-reported outcome measures. Given the rising incidence and costs for nonmelanoma skin cancer (NMSC) treatment, it is imperative to define quality measures specific to dermatologic surgery. OBJECTIVE: This study aims to evaluate patient-reported outcomes and satisfaction with Mohs micrographic surgery (MMS) together with patient and tumor factors to better define their use in developing treatment strategies and quality measures. METHODS AND MATERIALS: A prospective study was conducted among 226 patients undergoing MMS for treatment of NMSC. Patient demographics, quality of life, functional status, satisfaction, and prognostic factors were gathered. Postoperative outcomes were measured at 1 month and included patient-reported problems and provider-reported complications. Relationships between patient factors and outcomes were evaluated through statistical analysis. RESULTS: Average patient satisfaction in the domain of general satisfaction of the Patient Satisfaction Questionnaire-18 was 4.34 of 5. General patient satisfaction did not differ across age, final defect size, sex, or prognostic scores. At 1-month postoperatively, 97 percent of patients expressed willingness to undergo future MMS if indicated. CONCLUSION: Patients are generally satisfied with MMS for treatment of NMSC. Specific patient factors that may affect satisfaction include smoking status and anticoagulation use.

What Is New in Occupational Allergic Contact Dermatitis in the Year of the COVID Pandemic?

PURPOSE OF REVIEW: This article aims to summarize some recent trends in occupational allergic contact dermatitis (ACD), including dermatitis related to pandemic-level personal protective equipment in healthcare workers, hazards patients may experience when working from home, and occupational perspectives on the recent American Contact Dermatitis Society (ACDS) allergens of the year and ACDS Core Allergen Series updates. RECENT FINDINGS: Recent ACDS Allergens of the Year may be particularly relevant to healthcare workers, including isobornyl acrylate, which is present in glucose sensors and propylene glycol present in hand cleansers and disinfectants. Lavender, limonene, and linalool, all of which are new additions to the ACDS Core Allergen Series, have been reported as causes for occupational ACD in massage therapists and aromatherapists. Isothiazolinone allergy continues to rise in both consumer and occupational settings. Finally, the COVID-19 pandemic has resulted in a wave of occupational ACD in healthcare workers to personal protective equipment, and revealed new potential allergens for individuals working from home. Occupational allergic contact dermatitis continues to exert a significant occupational disease burden. Remaining aware of the current trends in allergens may allow for earlier recognition, diagnosis, and treatment, subsequently helping our patients to work in healthier and safer environments.

Gianotti-crosti syndrome in the setting of recent coronavirus disease-19 infection.

Since the onset of the COVID-19 pandemic, the growing body of literature has largely focused on the adult population. Reported symptoms among children appear to be consistent with those in adults, including fever, respiratory symptoms, and gastrointestinal symptoms, though children may experience an overall milder disease course. Viral exanthems with possible association to COVID-19 have been reported in pediatric patients. We describe a 10-month-old boy with Gianotti-Crosti syndrome in the setting of recent SARS-CoV-2 RT-PCR positive testing to increase physician awareness and add to the collection of cutaneous manifestations of COVID-19.

A systematic review of treatment strategies for erythrodermic psoriasis.

Background: Erythrodermic psoriasis (EP) is a severe, rare form of psoriasis that can be life threatening. Treatment of EP is usually based on anecdotal evidence or past clinical experience, which is in part due to the rarity and often emergent nature of this psoriasis subtype.Methods: In December 2018, a keyword search for 'erythrodermic psoriasis' and 'treatment' was conducted. All studies investigating treatment strategies for EP in at least 2 patients were included in this review.Results: The database search yielded 921 results, and 23 studies comprising over 200 patients with EP were included in the final analysis. Biologics including tumor necrosis factor inhibitors (infliximab [n = 4], etanercept [n = 2], and adalimumab [n = 1]), interleukin-17 inhibitors (secukinumab [n = 3], ixekizumab [n = 2], and brodalumab [n = 1]), ustekinumab (n = 4), and guselkumab (n = 1) have been shown to rapidly achieve clinical improvement in patients with EP. The included studies also demonstrated efficacy of systemic agents cyclosporine (n = 4), etretinate (n = 3), and methotrexate (n = 1).Conclusions: A fair number of poor-quality studies support the use of various biologic and systemic therapies in the treatment of EP. Treatment of EP should be based on the severity of the clinical scenario as well as patient comorbidities.

Risk for deep fungal infections during IL-17 and IL-23 inhibitor therapy for psoriasis.

Psoriasis is an inflammatory disease with both skin and joint manifestations. Focused biologics have been developed to target specific cytokines implicated in psoriasis and are becoming increasingly utilized. Recently, the advent of newer biologics, including IL-17, IL-12/IL-23, and IL-23 inhibitors, have garnered interest as promising treatments for psoriasis and other inflammatory conditions. Although IL-17 and IL-23 have been studied in the pathophysiology of psoriasis, they also play a central role in immunologic defenses, including those against fungi. Therefore, use of these interleukin inhibitors may theoretically impair the immune system against deep fungal infections. We reviewed the available literature investigating the risk for invasive fungal infections in patients treated with IL-17 and IL-23 inhibitors for psoriasis or other inflammatory conditions. Randomized controlled trials (RCTs), including extended trials and clinical trials, were reviewed, and we found that although there was a small number of patients who developed superficial candidiasis, there were no reports of invasive fungal disease. Although these results support the safety and the low risk for deep fungal infection with these biologics, caution is still warranted, as these medications are relatively new. Appropriate screening and management of fungal disease should still be practiced when utilizing these medications in the treatment of psoriasis and other inflammatory conditions.

The corporatization of dermatopathology.

The corporatization of dermatopathology has long preceded that of dermatology and has been driven by federal legislation and economic influences. Although the Clinical Laboratory Improvement Amendments and the Stark Law limited physician-owned laboratories, loopholes via the Safe Harbor Exemptions outlined in the Anti-Kickback Statute allowed corporate laboratories to flourish through relationships built by health information technology donations. The rise of corporatization has had widespread effects on the fields of dermatopathology and dermatology, resulting in reduced numbers of dermatology-trained dermatopathologists and decreased caseloads in academic institutions, potentially compromising dermatology residency education. Although there have been efforts to counteract these effects, more global changes will be required to alter the direction of this subspecialty.

Are biosimilars approved for use in psoriasis safe enough to replace leading biologic therapies? A review.

Introduction: Many tumor necrosis factor (TNF)-alpha 'biosimilar' agents have been approved for the treatment of psoriasis and other autoinflammatory conditions. These biosimilars have the same structure as the originator biologic and have been shown to be equivalent in terms of safety and efficacy. However, given the method by which biosimilars are manufactured, they are not exact replicas of the originator, unlike generic forms of non-biologic medications. Therefore, there is controversy regarding whether these agents should be considered interchangeable with their originator biologics.Areas covered: The objective of this review is to summarize the safety data for each of the approved TNF-alpha biosimilars to determine whether or not these agents have appropriate safety profiles to replace their originator biologics.Expert opinion: Based on extrapolation of phase III investigations in patients with rheumatologic diseases, each of the approved anti-TNF agents have comparable efficacy, tolerability, and safety profiles to their originators. Studies in patients with psoriasis are more limited. Transitioning from a biologic to its biosimilar has also been shown to be similarly safe and immunogenetic compared to maintenance therapy with the originator. More post-marketing studies are needed to demonstrate the long-term safety in patients with psoriasis.

Safety and Effectiveness of Anti-Tumor Necrosis Factor-Alpha Biosimilar Agents in the Treatment of Psoriasis.

Biologic drugs have revolutionized the treatment of psoriasis and other chronic inflammatory diseases. In recent years, many tumor necrosis factor-alpha 'biosimilar' agents have been developed. These biosimilars are similar in structure and function to their originator molecules, although they are not identical. Given that the safety and efficacy of the original biologic have already been proven, biosimilars are only required to show bioequivalence, or non-inferiority, to the reference biologic to be approved. Based on extrapolation of these non-inferiority data, biosimilars may be subsequently approved for all indications of the originator biologic, even without being directly studied in these various conditions. These biosimilar agents have been purported as a method to reduce the costs of biologic therapies, thereby increasing the accessibility of these medications and subsequently improving the treatment of psoriasis worldwide. The US Food and Drug Administration and/or the European Medicines Agency have approved biosimilars of adalimumab (Amjevita/Amgevita/Solymbic, Cyltezo, Imraldi/Hadlima, Hyrimoz/Hefiya/Halimatoz, Idacio, Hulio, Abrilada), etanercept (Erelzi, Benepali/Eticovo), and infliximab (Inflectra/Remsima, Renflexis/Flixabi, Ixifi/Zessly) for the treatment of psoriasis, and others are under review. There are many phase III data supporting the bioequivalence of these anti-tumor necrosis factor-alpha biosimilar agents in treating psoriasis and rheumatologic disease, which are discussed here. In general, these biosimilar agents have been shown to have equivalent efficacy, tolerability, and immunogenicity profiles compared to their originators in patients with rheumatologic disease, although studies in patients with psoriasis are fairly limited. Additional switching studies and post-marketing safety analyses are needed to assess the interchangeability of biosimilar agents with their reference products.