Secukinumab for the treatment of adult-onset pityriasis rubra pilaris: a single-arm clinical trial with transcriptomic analysis.

BACKGROUND: The pathogenesis of pityriasis rubra pilaris (PRP) is not completely understood, but interleukin (IL)-17 has been shown to play a critical role. There are no reliable immunomodulatory agents to treat PRP. We conducted an open-label, single-arm clinical trial of secukinumab, a monoclonal antibody that inhibits IL-17A, for the treatment of PRP. OBJECTIVES: To evaluate the clinical efficacy of secukinumab and define the transcriptomic landscape of PRP and its response to IL-17A blockade. METHODS: Twelve patients with PRP were recruited for an open-label trial of secukinumab. Patients received a 24-week course of secukinumab. The primary endpoint was a ≥ 75% reduction in Psoriasis Area and Severity Index (PASI 75) from baseline to week 28. Secondary endpoints included PASI 90, change in Physician's Global Assessment (PGA), and change in Dermatology Life Quality Index (DLQI). RNA sequencing was performed on lesional and nonlesional skin biopsies obtained at baseline and week 2. Sample groups were compared to identify differential gene expression and pathway enrichment. This trial was registered with ClinicalTrials.gov: 'Cosentyx (secukinumab) for the treatment of adult onset pityriasis rubra pilaris' - NCT03342573. RESULTS: At week 28, six of 11 patients (55%) achieved PASI 75, and three patients (27%) achieved PASI 90. PGA (P = 0.008) and DLQI scores (P = 0.010) showed significant improvement with treatment. No serious treatment-related adverse events were encountered. Treatment with secukinumab normalized transcriptional differences between lesional and nonlesional skin. Transcriptomic data from nonresponsive patients suggest that overactivity of innate immune pathways may be driving resistance to secukinumab. CONCLUSIONS: Secukinumab appears to be an effective treatment for PRP and warrants further investigation. PRP is a transcriptionally heterogeneous disease, reflecting its variable response to therapy. Agents targeting other IL-17 isoforms and innate immune mediators should be considered for future clinical trials. What is already known about this topic? The pathogenesis of pityriasis rubra pilaris is incompletely understood. Successful treatment has been reported with a variety of immunomodulatory agents, but disease is often refractory to therapy. Interleukin (IL)-17 is thought to drive keratinocyte proliferation and vascular dysfunction in this disease. A previous trial demonstrated efficacy of the anti-IL-17A drug ixekizumab for pityriasis rubra pilaris. What does this study add? Herein we describe the findings of a clinical trial of secukinumab, an anti-IL-17A monoclonal antibody, for the treatment of pityriasis rubra pilaris. Secukinumab was effective in treating pityriasis rubra pilaris. Our transcriptomic data give new insight into the expressional changes that occur in response to secukinumab and suggest mechanisms of treatment resistance.

From dermatological conditions to COVID-19: Reasoning for anticoagulation, suppression of inflammation, and hyperbaric oxygen therapy.

COVID-19 generates a complex systemic inflammatory response that can lead to death due to wide macrophage activation, endothelial damage, and coagulation in critically ill patients. SARS-CoV-2-induced lung injury due to inflammatory mediated thrombosis could be similar to the livedoid vasculopathy in the skin, supporting a translational comparison of these clinical settings. In this article, we discuss anticoagulation, suppression of inflammatory response, and hyperbaric oxygen therapy in the context of severe COVID-19 and livedoid vasculopathy.

Livedoid vasculopathy in 75 Brazilian patients in a single-center institution: Clinical, histopathological and therapy evaluation.

This study presents a single center experience with livedoid vasculopathy (LV). A rare disease that can lead to severe quality of life impairment. Characterize clinical data of LV patients at the Dermatology Division at the University of São Paulo. A retrospective and transversal study was conducted, from 1 January 2005 to 31 December 2019. About 75 patients diagnosed as LV and confirmed by skin biopsy were included. Epidemiology, clinical appearance, histopathology data, and treatment history were observed. There were 78.66% Caucasian women, with a mean age of 39.9 years. Frequent cutaneous manifestations were ulcers, atrophic blanche-like scars, hyperpigmentation, purpuras, telangiectasias, and livedo racemosa. Pain, pruritus, and hypoesthesia were the main symptoms. After treatment, almost 40% of cases relapsed during spring and summer months. About 66% of cases had thrombophilia factors associated, such as high levels of lipoprotein(a). Frequent treatments included acetylsalicylic acid, pentoxifylline, and diosmin with hesperidin. Not being a prospective study. This research provides useful data on Latin American LV patients, indicating multifactorial conditions involved in LV pathogenesis. An extensive work-up including autoimmune laboratory tests, thrombophilia factors, and other conditions associated with venous stasis should be part of LV investigation and controlled to improve treatment response.

Potential interactions of SARS-CoV-2 with human cell receptors in the skin: Understanding the enigma for a lower frequency of skin lesions compared to other tissues.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) represents a new public health problem, with a total of 10.577.263 documented COVID-19 cases worldwide and 513.441 deaths up to the present date. Few cases of disease-related cutaneous manifestations have been reported in the literature, and such manifestations are scarce. Integumentary manifestations from COVID-19 include exanthemas and papular dermatoses, urticarial eruptions, atopic dermatitis, vesiculobullous lesions and skin signs of hypercoagulable states, such as acral ischaemia, livedo and retiform purpura. Most common extracutaneous manifestations from the disease include headache, cough, anosmia, ageusia, fever, dyspnoea, nausea, diarrhoea and cardiovascular events. The objectives of this review were to discuss the role of human cell receptors described as interaction targets of SARS-CoV-2, as well to understand the current state of knowledge on skin expression of these receptors, in order to substantiate future research. The authors present a thorough literature review on SARS-CoV-2 and its possible interaction with cell receptors and human tissues including the skin. They discuss a molecular hypothesis to explain the lower prevalence of dermatological manifestations from direct SARS-CoV-2 infection. Distinct human cell receptors binding the virus appear to be less expressed in the skin compared to other organs. Additionally, the presence of resolvins and the disintegrin metalloprotease ADAM17 provide a putative protection to the skin, explaining the majority of COVID-19 manifestations to be extracutaneous. This review represents an excellent opportunity for future studies using skin biopsies from COVID-19 patients to investigate molecular expression in the pathophysiology of cutaneous manifestations of the disease.

A rare case of multiple variants of porokeratosis in the same patient: The clue of dermoscopy for diagnosis and therapeutical update.

Porokeratosis (PK) consists of abnormal keratinization of the epidermis of uncertain etiology and was first described by Mibelli in 1893. Multiple clinical variants of porokeratosis are recognized. The following is a case of a young male who presented more than one form of PK simultaneously. The hallmark of PK is the cornoid lamella, which can be identified in histopathology, and sometimes, as in our case, dermoscopy examination is the clue for diagnosis. This condition is often misdiagnosed and, therefore, not appropriately treated. Several treatment options are available and each clinical form may respond better to a specific therapy. However, consistency in treatment guidelines is still lacking.

A Randomized, Controlled Pilot Trial Comparing Platelet-Rich Plasma to Topical Minoxidil Foam for Treatment of Androgenic Alopecia in Women.

BACKGROUND: Androgenic alopecia (AGA) is a common hair loss disorder. Studies have demonstrated successful treatment with platelet-rich plasma (PRP) in men, but studies in women are few. OBJECTIVE: To evaluate PRP in the treatment of AGA in women, compared with topical minoxidil. MATERIALS AND METHODS: Twenty women with AGA received topical minoxidil for 12 weeks and injectable PRP for 12 weeks in a randomized crossover design with an 8-week washout between treatments. Standardized TrichoScan analysis and quality-of-life questionnaires were assessed at baseline and 12-week follow-up for each treatment. RESULTS: After PRP, significant increases from baseline to Week 12 in TrichoScan analysis hair count (p = .002) and vellus hair density (p = .009) occurred. However, minoxidil resulted in significant increases in hair count (p < .001), vellus hair density (p = .03), terminal hair density (p = .004), and cumulative thickness (p = .004). Several quality of life responses improved from baseline to Week 12 after PRP treatment, whereas no improvements were noted after minoxidil. CONCLUSION: Platelet-rich plasma is an effective treatment for hair regrowth in female AGA, although not as effective as minoxidil. However, the improved quality of life responses after PRP, but not minoxidil, suggest a potential overall greater degree of satisfaction with PRP. LEVELS OF EVIDENCE: I. CLINICAL TRIAL REGISTRATION: NCT03488108.

Analysis of serum levels and cutaneous expression of lipoprotein (a) in 38 patients with livedoid vasculopathy.

BACKGROUND: Coagulation disorders contribute to the development of livedoid vasculopathy (LV). Elevated plasma levels of lipoprotein(a) [Lp(a)] are an independent risk factor for the development of cardiovascular disease and associated with hypercoagulable states. Increased serum Lp(a) levels have been reported in patients with LV and may have an important role in the pathogenesis of LV. OBJECTIVES: To investigate Lp(a) expression in skin lesions and circulating serum Lp(a) levels in patients with LV. METHODS: Skin biopsy samples from 38 patients (27 women and 11 men) with active lesions diagnosed as LV and 9 samples of normal skin (5 women and 4 men) from control patients without LV were evaluated for skin expression of Lp(a) by immunohistochemistry. Plasma levels of Lp(a) were analyzed by immunoturbidimetry. RESULTS: We found that lesional skin in patients with LV expressed 10-fold higher Lp(a) immunostaining than controls. High plasma levels of Lp(a) were observed in LV patients. We did not find a correlation (P = .02) between expression of Lp(a) in the skin and plasma levels of Lp(a) in patients with LV. CONCLUSIONS: Increased Lp(a) expression in lesional skin of LV patients suggests the role of Lp(a) in the thrombo-occlusive vasculopathy observed in this disease.

Sudden Sensorineural Hearing Loss in Patient Incidental to Treatment With Hyaluronic Acid Filler.

Hyaluronic acid fillers comprise a major component of aesthetic practice with few serious adverse effects. Hearing loss has not been previously associated with hyaluronic acid filler. The authors describe a case in which a patient developed sudden sensorineural hearing loss 1 day after filler injection into the nasolabial folds. Audiogram showed moderately severe sensorineural loss, and MRI revealed no abnormalities. Despite transtympanic steroid injections and hyperbaric oxygen therapy, the hearing loss persists at the time of writing. Although no causal relationships can be drawn from this case alone, this case serves to reinforce the importance of continued vigilance for future occurrences to minimize the potential risk of this serious adverse event.

High-risk adverse drug reactions: consideration of limited dialysis therapy for toxic epidermal necrolysis (TEN).

Toxic epidermal necrolysis (TEN) is a rare but often lethal drug reaction involving the skin. Treatment is often centered around suppurative care, and the mortality rate remains unacceptably high, although the clinical and epidemiological features of TEN have been well documented for decades. Recent studies have placed an emphasis on certain medications in the pathophysiology of severe TEN, and our colleagues previously reported several cases of clinical improvement in TEN patients following hemodialysis. Here, we discuss the major considerations for initiating dialysis in TEN patients. By doing so, we hope to encourage others to explore this potential avenue for treating TEN, one of the most serious medical emergencies in the field of dermatology.

An Academic Dermatology Center's Structured Platelet-rich Plasma Approach to Patients with Androgenetic Alopecia.

Androgenetic alopecia (AGA) is a prevalent cause of hair loss with complex pathophysiologic mechanisms that pose challenges for effective treatment. Despite various therapeutic approaches yielding only partial results, regenerative treatments, such as platelet-rich plasma (PRP), have gained popularity. However, the lack of standardized PRP practices, encompassing product preparation and application, has been a significant concern. This article aims to contribute to fill this gap by presenting a comprehensive overview of PRP practices at a large academic center. Through detailing our protocols, this work not only contributes to the understanding of AGA treatment but also emphasizes the crucial aspect of treatment standardization in the context of PRP therapy. By providing a practical representation of our institutional PRP practices, we aim to contribute to the ongoing discourse on refining and implementing standardized protocols, fostering reproducibility, and improving clinical outcomes in the management of AGA.

Evaluation of Platelet-rich Plasma and Microneedling for Facial Skin Rejuvenation.

Background: The regenerative properties of platelet growth factors make platelet-rich-plasma (PRP) an attractive modality for treatment of aging skin. The main objective of this study was to determine efficacy and safety of PRP injections and microneedling compared with saline injections in women with aging skin of the face. Methods: In this prospective, randomized clinical trial, 18 women with facial aging were randomized to receive either PRP injections to the unilateral face and saline injections to the contralateral side, or vice versa. Microneedling was performed after injections on the entire face. Physician assessment, photographs, and treatment satisfaction questionnaires were used for outcome assessment at baseline and 16- and 24-week follow-ups. Results: There was no evidence of improvement and suggestion of worsening in skin laxity and rhytides from baseline to weeks 4, 16, and 24 for PRP and saline (all P ≤ 0.004) and no notable difference in skin roughness between baseline and follow-up time points for PRP or saline (all P ≥ 0.19). The degree of change in skin laxity, rhytides, and skin roughness from baseline to follow-up time points was similar for PRP and saline. All patients experienced some degree of pain/discomfort and burning/stinging sensation at treatment weeks 4, 8, and 12 for both saline and PRP. Conclusions: PRP injections did not seem to be effective for treatment of aging skin of the face in women, with no notable macroscopic improvement in appearance when compared with baseline or saline injections. Advanced age of study participants (>45 years) and less-sensitive methods of evaluation may be potential contributing factors to the lack of detected response.

A Pilot, Randomized, Single-Blind, Controlled Study Evaluating the Use of Platelet Rich Plasma (PRP) for Hand Skin Rejuvenation.

BACKGROUND: The presence of various growth factors in platelets makes platelet rich plasma a powerful tool in the stimulation of collagen regeneration in aging skin. The main objective of this study was to determine efficacy and safety of platelet rich plasma compared to saline solution in women with aging skin of the hands. METHODS: In this prospective, randomized clinical trial, eighteen women with hand aging received PRP injections every 4 weeks into the unilateral dorsal hand for 12 weeks total; with saline injections into the contralateral hand in a randomized, controlled, single-blind fashion. Physician assessment, photographs and quality-of-life questionnaires were used for assessment at baseline; 12- and 24-week follow-up. RESULTS: The majority of patients reported pain and discomfort along with a burning/stinging sensation in both PRP and saline treated hands with no significant differences noted in any patient outcome measures between the two treatments (all P≥0.25). No differences were reliably detected between the treatment hands by a blinded investigator comparing before and after clinical photographs of the hands. CONCLUSION: Three injections of PRP spaced 4 weeks apart did not appear to be effective for treatment of aging skin of the hands in women, with no noted difference as compared with baseline, or saline injection. Although age > 45 years may be a factor accounting for non-response (i.e., subtle skin changes are difficult to appreciate, and possible limited platelet regenerative capacity in advanced age) it appears that PRP is not a reliable cosmetic option for management of hand aging.

Case of vago-glossopharyngeal neuralgia secondary to metastatic oropharyngeal cancer.

Glossopharyngeal neuralgia (GN) is a rare pain syndrome caused by compression of the glossopharyngeal nerve. It is typically idiopathic and often goes misdiagnosed because of its similarities to trigeminal neuralgia. Vago-glossopharyngeal neuralgia, an even rarer subset of GN, occurs when the pain is accompanied by syncope and/or arrhythmia. Here, we present the case of a 54-year-old man with oropharyngeal cancer that metastasised to areas within his left carotid sheath. He presented with numerous intermittent episodes of pain, accompanied by vagal episodes. While this presentation is similarly described in prior case reports, our case is unique in that the syndrome occurred as a direct sequelae of a metastatic tumour completely encasing the left internal carotid artery.

Valchlor® in the Treatment of Lichen Planopilaris and Frontal Fibrosing Alopecia: A Single Arm, Open-label, Exploratory Study.

BACKGROUND: Lichen Planopilaris (LPP) is a lymphocyte-mediated scarring alopecia that frequently is treatment resistance to both topical and systemic therapies. AIMS AND OBJECTIVES: The object of this pilot study was to assess the effectiveness of topical mechlorethamine 0.016% gel (Valchlor®) in decreasing disease activity in LPP and the related clinical variant frontal fibrosing alopecia (FAA). METHODS: Twelve patients with biopsy-proven LPP/FAA who failed prior topical or systemic therapy with active disease were included. Participants applied mechlorethamine 0.016% gel to involved areas daily for 24 weeks. Outcome measures included LPP Activity Index (LPPAI) score, Physician Global Assessment (PGA) score, Dermatology Quality of Life Index (DQLI) score, and phototrichograms assessing follicular counts before and after six months of therapy. RESULTS: LPP Activity Index (LPPAI) before and after treatment was significantly different (5.0 before treatment, 2.0 after treatment; p value=0.006). Mean follicular density and follicular units were unchanged during the treatment period. CONCLUSION: Treatment with mechlorethamine 0.016% gel for 24 weeks resulted in statistically significant improvement of LLP/FFA with no change in phototrichogram parameters. Treatment duration was limited by high rate of contact dermatitis. Further investigation to optimize dosing frequency and to assess the role of combination topical therapy is needed.

Adipose-derived cellular and cell-derived regenerative therapies in dermatology and aesthetic rejuvenation.

Cellular and cell-derived components of adipose-derived tissue for the purposes of dermatologic and aesthetic rejuvenation applications have become increasingly studied and integrated into clinical practice. These components include micro-fragmented fat (nanofat), the stromal vascular fraction (SVF), adipose-derived mesenchymal stem cells (ASC), and extracellular vesicles (EVs), which have all shown capability to repair, regenerate, and rejuvenate surrounding tissue. Various aesthetic applications including hair growth, scar reduction, skin ischemia-reperfusion recovery, and facial rejuvenation are reviewed. In particular, results from preclinical and clinical studies are discussed, with a focus on clarification of nomenclature.