Precision Dermatology: A Review of Molecular Biomarkers and Personalized Therapies.

The evolution of personalized medicine in dermatology signifies a transformative shift towards individualized treatments, driven by the integration of biomarkers. These molecular indicators serve beyond diagnostics, offering insights into disease staging, prognosis, and therapeutic monitoring. Specific criteria guide biomarker selection, ensuring attributes like specificity, sensitivity, cost feasibility, stability, rapid detection, and reproducibility. This literature review, based on data from PubMed, SCOPUS, and Web of Science, explores biomarkers in Hidradenitis Suppurativa (HS), Psoriasis, Atopic Dermatitis (AD), Alopecia Areata (AA), Vitiligo, and Chronic Spontaneous Urticaria (CSU). In HS, TNF-α, IL-1ß, and MMPs serve as biomarkers, influencing targeted therapies like adalimumab and anakinra. Psoriasis involves biomarkers such as TNF-α, IL-23, and HLA genes, shaping treatments like IL23 and IL17 inhibitors. AD biomarkers include ECP, IL-4, IL-13, guiding therapies like dupilumab and tralokinumab. For AA, lipocalin-2, cytokines, and genetic polymorphisms inform JAK inhibitors' use. Vitiligo biomarkers range from cytokines to genetic markers like TYR, TYRP1, guiding treatments like JAK inhibitors. CSU biomarkers encompass IgE, cytokines, and autologous serum tests, influencing therapies like omalizumab and cyclosporine. Comparing conditions, common proinflammatory markers reveal limited specificity. While some biomarkers aid diagnosis and standard treatments, others hold more scientific than clinical value. Precision medicine, driven by biomarkers, has shown success in skin malignancies. Future directions involve AI-powered algorithms, nanotechnology, and multi-omics integration for personalized dermatological care.

From Tugs to Treatments: A Systematic Review on Pharmacological Interventions for Trichotillomania.

Trichotillomania (TTM) is a psychiatric disorder with dermatologic consequences, characterized by recurrent hair-pulling. It affects 1-3% of the population, and often coexists with other psychiatric disorders, leading to emotional distress. Effective management of TTM can be challenging due to underdiagnosis, symptom heterogeneity, and stigma. Pharmacological interventions, including SSRIs and NAC are commonly utilized. The objective of this review is to assess the existing literature on pharmacotherapy for trichotillomania and identify potential avenues for future research and treatment advancements. A systematic review of the literature was performed using PubMed and Scopus databases within the last 10 years. Included studies assessed pharmacotherapy for trichotillomania and provided insights into current evidence and potential directions for future research and treatment advancements. In total, 23 articles were identified that met inclusion criteria. The most successful interventions were NAC, aripiprazole, and monoamine oxidase inhibitors. NAC was identified as the most impressive adjunctive therapy in treatment through its mechanism of decreased glutamate-induced excitatory neuronal damage, with adjunctive antioxidant properties. Most of the other therapeutics that were identified require further research and controlled trials to validate their findings. Even if successful therapeutic outcomes are achieved, it is important to consider the patient's comorbidities and to combine pharmacologic interventions with behavioral therapy interventions to comprehensively manage TTM.

The Pathophysiology, Prognosis and Treatment of Hypertension in Females from Pregnancy to Post-menopause: A Review.

PURPOSE OF REVIEW: We summarise the physiological changes and risk factors for hypertension in females, potential sex-specific management approaches, and long-term prognosis. KEY FINDINGS: Pregnancy and menopause are two key phases of the life cycle where females undergo significant biological and physical changes, making them more prone to developing hypertension. Gestational hypertension occurs from changes in maternal cardiac output, kidney function, metabolism, or placental vasculature, with one in ten experiencing pregnancy complications such as intrauterine growth restriction and delivery complications such as premature birth. Post-menopausal hypertension occurs as the protective effects of oestrogen are reduced and the sympathetic nervous system becomes over-activated with ageing. Increasing evidence suggests that post-menopausal females with high blood pressure (BP) experience greater risk of cardiovascular events at lower BP thresholds, and greater vulnerability to treatment-related adverse effects. Hypertension is a key risk factor for cardiovascular disease in females. Current BP treatment guidelines and recommendations are similar for both sexes, without addressing sex-specific factors. Future investigations into ideal diagnostic thresholds, BP control targets and treatment regimens in females are needed.

Biologics for Treatment of Pityriasis Rubra Pilaris: A Literature Review.

OBJECTIVE: To describe the published efficacy and adverse event rates associated with existing biologics for the treatment of pityriasis rubra pilaris (PRP). DATA SOURCES: A literature review using the PubMed database (January 1990-July 2023) was conducted. Multiple search combinations were conducted using "pityriasis rubra pilaris" and various biologics as keywords to identify relevant articles. STUDY SELECTION AND DATA EXTRACTION: Inclusion criteria included all study types that were published within the past 30 years in English and mentioned at least one biologic and PRP. A preliminary search yielded a total of 499 results. After screening using inclusion and exclusion criteria, 77 relevant articles (69 case reports, 5 case series, 2 clinical trials, and 1 retrospective analysis) were analyzed. DATA SYNTHESIS: TNF-α inhibitors have been evaluated and are effective in treating PRP. However, recent treatment with anti-interleukin (IL)-17 and anti-IL-23 therapies such as ustekinumab, secukinumab, and ixekizumab are emerging as new treatment options with a mean improvement in PRP Area and Severity Index scores, change in severity of erythema, scaling, and thickness of PRP lesions. From initial clinical trials, secukinumab and ixekizumab are promising treatment options for achieving remission. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review compares the efficacy for numerous biologics and a discussion to guide clinicians on benefits and risks in choosing a biologic for PRP patients. CONCLUSIONS: Biologics may be a favourable treatment option leading to greater patient adherence due to reduced dosing frequencies, improvement in quality of life, and reduction in frequency and severity of flares.

Transforming blood pressure control in primary care through a novel remote decision support strategy based on wearable blood pressure monitoring: The NEXTGEN-BP randomized trial protocol.

BACKGROUND: Despite high blood pressure being the leading preventable risk factor for death, only 1 in 3 patients achieve target blood pressure control. Key contributors to this problem are clinical inertia and uncertainties in relying on clinic blood pressure measurements to make treatment decisions. METHODS: The NEXTGEN-BP open-label, multicenter, randomized controlled trial will investigate the efficacy, safety, acceptability and cost-effectiveness of a wearable blood pressure monitor-based care strategy for the treatment of hypertension, compared to usual care, in lowering clinic blood pressure over 12 months. NEXTGEN-BP will enroll 600 adults with high blood pressure, treated with 0 to 2 antihypertensive medications. Participants attending primary care practices in Australia will be randomized 1:1 to the intervention of a wearable-based remote care strategy or to usual care. Participants in the intervention arm will undergo continuous blood pressure monitoring using a wrist-wearable cuffless device (Aktiia, Switzerland) and participate in 2 telehealth consultations with their primary care practitioner (general practitioner [GP]) at months 1 and 2. Antihypertensive medication will be up-titrated by the primary care practitioner at the time of telehealth consults should the percentage of daytime blood pressure at target over the past week be <90%, if clinically tolerated. Participants in the usual care arm will have primary care consultations according to usual practice. The primary outcome is the difference between intervention and control in change in clinic systolic blood pressure from baseline to 12 months. Secondary outcomes will be assessed at month 3 and month 12, and include acceptability to patients and practitioners, cost-effectiveness, safety, medication adherence and patient engagement. CONCLUSIONS: NEXTGEN-BP will provide evidence for the effectiveness and safety of a new paradigm of wearable cuffless monitoring in the management of high blood pressure in primary care. TRIAL REGISTRATION: ACTRN12622001583730.

The prevalence and impact of orthostatic intolerance in young women across the hypermobility spectrum.

Orthostatic intolerance (OI) is frequently reported in young women with generalized hypermobility spectrum disorder (G-HSD) and hypermobile EDS (hEDS). However, it remains currently unclear whether OI is a comorbidity or fundamental part of the pathophysiology of G-HSD or hEDS. This study investigated the prevalence and impact of OI in young women across the hypermobility spectrum. Forty-five women (14-30 years, 15 controls, 15 G-HSD, and 15 hEDS) undertook a head-up tilt (HUT) and active stand test. Postural Orthostatic Tachycardia Syndrome (POTS) and Orthostatic Hypotension (OH) were assessed using age-related criteria. Autonomic dysfunction and quality-of-life questionnaires were also completed. The prevalence of POTS was higher in women with G-HSD than hEDS and control groups during HUT (43% vs. 7% and 7%, respectively, p < 0.05), but similar between groups during the active stand (47%, 27%, and 13% for G-HSD, hEDS, and control, respectively). No participants had OH. hEDS and G-HSD participants reported more severe orthostatic symptoms and poorer quality of life than controls. Although POTS was observed in hypermobile participants, there is no conclusive evidence that its prevalence differed between groups due to differences between the HUT and active stand assessments. Nevertheless, OI and broader autonomic dysfunction impacted on their quality of life.

Don't Turn Off the Tap! The Importance of Discovery Science to the Australian Cardiovascular Sector and Improving Clinical Outcomes Into the Future.

Despite significant advances in interventional and therapeutic approaches, cardiovascular disease (CVD) remains the leading cause of death and mortality. To lower this health burden, cardiovascular discovery scientists need to play an integral part in the solution. Successful clinical translation is achieved when built upon a strong foundational understanding of the disease mechanisms involved. Changes in the Australian funding landscape, to place greater emphasis on translation, however, have increased job insecurity for discovery science researchers and especially early-mid career researchers. To highlight the importance of discovery science in cardiovascular research, this review compiles six science stories in which fundamental discoveries, often involving Australian researchers, has led to or is advancing to clinical translation. These stories demonstrate the importance of the role of discovery scientists and the need for their work to be prioritised now and in the future. Australia needs to keep discovery scientists supported and fully engaged within the broader cardiovascular research ecosystem so they can help realise the next game-changing therapy or diagnostic approach that diminishes the burden of CVD on society.

Measuring Arterial Stiffness in Animal Experimental Studies.

The arterial wall is a composite material of elastin, collagen, and extracellular matrix with acutely modifiable material properties through the action of smooth muscle cells. Therefore, arterial stiffness is a complex parameter that changes not only with long-term remodeling of the wall constituents but also with acute contraction or relaxation of smooth muscle or with changes in the acute distending pressure to which the artery is exposed. It is not possible to test all these aspects using noninvasive or even invasive techniques in humans. Full characterization of the mechanical properties of the artery and the specific arterial factors causing changes to stiffness with disease or modified lifestyle currently require animal studies. This article summarizes the major in vivo and ex vivo techniques to measure the different aspects of arterial stiffness in animal studies.

May Measurement Month 2019: an analysis of blood pressure screening results from Australia.

May Measurement Month (MMM) is an annual global blood pressure (BP) screening campaign aimed at obtaining standardized BP measurements and other relevant health information from members of the community to increase awareness of elevated BP and the associated risks. Adults (≥18 years) were recruited through opportunistic sampling across the various Australian states during May 2019. Three BP readings were recorded in a standardized manner for each participant, and data on lifestyle factors and comorbidities were collected. Hypertension was defined as a systolic BP ≥140 mmHg, or a diastolic BP ≥90 mmHg (according to the MMM protocol) or taking antihypertensive medication. Multiple imputation was used to estimate participants' mean BP where three readings were not available. Of the 2877 participants, 901 (31.3%) had hypertension of whom 455 (50.5%) were aware of their condition, and 366 (40.6%) were on antihypertensive medication. Of those taking antihypertensive medication, 54.3% were controlled to <140/90 mmHg with the remaining 45.7% of participants inadequately treated. Approximately 74% of treated patients were on a single antihypertensive medication. The MMM campaign provides an important platform for standardized compilation of BP data and creation of BP awareness in Australia and other nations worldwide. Data from the 2019 MMM campaign highlight that BP control rates in Australia remain unacceptably low.

May Measurement Month 2018: an analysis of blood pressure screening results from Australia.

May Measurement Month (MMM), originally initiated as a temporary solution to address the lack of blood pressure (BP) screening programs worldwide, emerged as an effective annual campaign to increase the awareness of hypertension. MMM18, a cross-sectional survey of volunteers aged ≥18 years was carried out during May 2018 predominantly in capital cities across Australia following the standard MMM protocol. Blood pressure screening along with additional information including anthropometric data and responses to questionnaires on demographic, lifestyle, and environmental factors were collected from 3 352 individuals across Australia. After multiple imputation, 1 026 (30.6%) adult Australians had hypertension. Of the 2 936 individuals not on antihypertensive treatment, 610 (20.8%) were hypertensive, and 237 (57.1%) of the 416 individuals receiving antihypertensive treatment had uncontrolled BP. In line with MMM17 results and other previous surveys, MMM18 revealed that close to one-third of the screened population (30.6%) had hypertension, 57.1% of individuals treated with BP-lowering medication remained uncontrolled indicating suboptimal management of the condition in the majority of patients. Most importantly, only 49.0% of those with hypertension were aware of their elevated BP, highlighting lack of awareness of elevated BP in nearly half of the affected population. Elevated BP was directly associated with alcohol consumption, overweight, and obesity. Our findings demonstrate the need for (i) continued efforts to increase BP awareness in the population, (ii) optimization of BP management strategies, and (iii) tackling some of the major contributors to BP elevation, including alcohol consumption and obesity.

Central aortic pressure improves prediction of cardiovascular events compared to peripheral blood pressure in short-term follow-up of a hypertensive cohort.

Objective: The aim of this study was to assess indices of a comprehensive panel of central aortic pressure and arterial stiffness for prediction of cardiovascular events in a hypertensive cohort.Methods: Noninvasive measurements of central aortic blood pressure, brachial pressure, wave reflection augmentation index, pressure amplification, pulse wave velocity (PWV) and carotid intima-media thickness (IMT) were obtained in 675 hypertensive patients (age 61 ± 9 years, 425 males) for a mean follow-up period 25 ± 4 months. The primary endpoints were defined as cardiovascular disease (CVD) events or death from CVD.Results: After adjusting for confounding factors, central systolic (cSBP) and pulse pressure (cPP) showed higher hazard ratios (HR/10 mmHg) for cardiovascular events (CV) compared to peripheral pressure indices (pSBP, pPP) at age >60 years (cSBP: HR = 1.18, pSBP: HR = 1.17, p = 0.034; cPP: HR = 1.28, pPP: HR = 1.2, p = 0.019). Each SD increase in IMT and in central augmented pressure (cAP) entailed a 1.4 times higher risk of increased total events in elderly patients (age >60 years). For males, each SD increase in cAP was associated with 1.36 times higher risk of increased total events. For females, each SD increase in cAIx and cAP was associated with 0.4 and 0.5 times lower risk of increased total and major CV, respectively. This sex difference is most likely due to lack of age-related increase of cAIx in females after age >60 years compared to males.Conclusions: Central pressure improved prediction of CVD compared to peripheral pressure during a relatively short-term follow up of approximately 2 years at age >60 years.

Mechanism underlying the heart rate dependency of wave reflection in the aorta: a numerical simulation.

Arterial wave reflection has been shown to have a significant dependence on heart rate (HR). However, the underlying mechanisms inherent in the HR dependency of wave reflection have not been well established. This study aimed to investigate the potential mechanisms and role of arterial viscoelasticity using a 55-segment transmission line model of the human arterial tree combined with a fractional viscoelastic model. At varying degrees of viscoelasticity modeled as fractional order parameter α, reflection magnitude (RM), reflection index (RI), augmentation index (AIx), and a proposed novel normalized reflection coefficient (Γnorm) were estimated at different HRs from 60 to 100 beats/min with a constant mean flow of 70 ml/s. RM, RI, AIx, and Γnorm at the ascending aorta decreased linearly with increasing HR at all degrees of viscoelasticity. The means ± SD of the HR dependencies of RM, RI, AIx, and Γnorm were -0.042 ± 0.004, -0.018 ± 0.001, -1.93 ± 0.55%, and -0.037 ± 0.002 per 10 beats/min, respectively. There was a significant and nonlinear reduction in RM, RI, and Γnorm with increasing α at all HRs. In addition, HR and α have a more pronounced effect on wave reflection at the aorta than at peripheral arteries. The potential mechanism of the HR dependency of wave reflection was explained by the inverse dependency of the reflection coefficient on frequency, with the harmonics of the pulse waveform moving toward higher frequencies with increasing HR. This HR dependency can be modulated by arterial viscoelasticity. NEW & NOTEWORTHY This in silico study addressed the underlying mechanisms of how heart rate influences arterial wave reflection based on a transmission line model and elucidated the role of arterial viscoelasticity in the dependency of arterial wave reflection on heart rate. This study provides insights into wave reflection as a frequency-dependent phenomenon and demonstrates the validity of using reflection magnitude and reflection index as wave reflection indexes.

Cerebral Haemodynamics: Effects of Systemic Arterial Pulsatile Function and Hypertension.

PURPOSE OF REVIEW: Concepts of pulsatile arterial haemodynamics, including relationships between oscillatory blood pressure and flow in systemic arteries, arterial stiffness and wave propagation phenomena have provided basic understanding of underlying haemodynamic mechanisms associated with elevated arterial blood pressure as a major factor of cardiovascular risk, particularly the deleterious effects of isolated systolic hypertension in the elderly. This topical review assesses the effects of pulsatility of blood pressure and flow in the systemic arteries on the brain. The review builds on the emerging notion of the "pulsating brain", taking into account the high throughput of blood flow in the cerebral circulation in the presence of mechanisms involved in ensuring efficient and regulated cerebral perfusion. RECENT FINDINGS: Recent studies have provided evidence of the relevance of pulsatility and hypertension in the following areas: (i) pressure and flow pulsatility and regulation of cerebral blood flow, (ii) cerebral and systemic haemodynamics, hypertension and brain pathologies (cognitive impairment, dementia, Alzheimer's disease), (iii) stroke and cerebral small vessel disease, (iv) cerebral haemodynamics and noninvasive estimation of cerebral vascular impedance, (v) cerebral and systemic pulsatile haemodynamics and intracranial pressure, (iv) response of brain endothelial cells to cyclic mechanical stretch and increase in amyloid burden. Studies to date, producing increasing epidemiological, clinical and experimental evidence, suggest a potentially significant role of systemic haemodynamic pulsatility on structure and function of the brain.

Arterial viscoelasticity: role in the dependency of pulse wave velocity on heart rate in conduit arteries.

Experimental investigations have established that the stiffness of large arteries has a dependency on acute heart rate (HR) changes. However, the possible underlying mechanisms inherent in this HR dependency have not been well established. This study aimed to explore a plausible viscoelastic mechanism by which HR exerts an influence on arterial stiffness. A multisegment transmission line model of the human arterial tree incorporating fractional viscoelastic components in each segment was used to investigate the effect of varying fractional order parameter (α) of viscoelasticity on the dependence of aortic arch to femoral artery pulse wave velocity (afPWV) on HR. HR was varied from 60 to 100 beats/min at a fixed mean flow of 100 ml/s. PWV was calculated by intersecting tangent method (afPWVTan) and by phase velocity from the transfer function (afPWVTF) in the time and frequency domain, respectively. PWV was significantly and positively associated with HR for α ≥ 0.6; for α = 0.6, 0.8, and 1, HR-dependent changes in afPWVTan were 0.01 ± 0.02, 0.07 ± 0.04, and 0.22 ± 0.09 m/s per 5 beats/min; HR-dependent changes in afPWVTF were 0.02 ± 0.01, 0.12 ± 0.00, and 0.34 ± 0.01 m/s per 5 beats/min, respectively. This crosses the range of previous physiological studies where the dependence of PWV on HR was found to be between 0.08 and 0.10 m/s per 5 beats/min. Therefore, viscoelasticity of the arterial wall could contribute to mechanisms through which large artery stiffness changes with changing HR. Physiological studies are required to confirm this mechanism.NEW & NOTEWORTHY This study used a transmission line model to elucidate the role of arterial viscoelasticity in the dependency of pulse wave velocity on heart rate. The model uses fractional viscoelasticity concepts, which provided novel insights into arterial hemodynamics. This study also provides a means of assessing the clinical manifestation of the association of pulse wave velocity and heart rate.

Unraveling the mirage of fairness cream commercials: A cross-sectional analysis of commercials from South Asia.

BACKGROUND: Fairness products are an essential component of daily beauty routines for many individuals in subcontinental Asia. However, it is important to be aware that these products often contain ingredients that can be detrimental to the skin and are banned in several developed countries. OBJECTIVE: Our study aims to analyze the content of fairness cream commercials in order to gain a deeper understanding of the information used to persuade and influence consumers to use these products. METHODS: Fairness cream commercials originating from countries in subcontinental Asia, including India, Pakistan, Bangladesh, Sri Lanka, and Nepal, were specifically searched and analyzed on the YouTube platform. RESULTS: An analysis of 152 fairness cream commercials on YouTube identified 84.21% of commercials targeted female consumers, while only 15.79% targeted male consumers. 77.63% of commercials used celebrities in their commercials and 47.37% of commercials mentioned specific ingredients. CONCLUSIONS: Based on our findings, it is crucial for dermatologists to take an active role in educating patients and consumers about the potential risks associated with certain ingredients found in fairness creams. Dermatologists should emphasize the importance of prioritizing overall skin health rather than solely focusing on skin lightening.

Blood pressure time at target and its prognostic value for cardiovascular outcomes: a scoping review.

The proportion of time that blood pressure (BP) readings are at treatment target levels, commonly referred to as time at target or time in therapeutic range (BP-TTR), is emerging as a useful measure for evaluating hypertension management effectiveness and assessing longitudinal BP control. However, method of determination for BP-TTR differs across studies. This review identifies variations in BP-TTR determination methodologies and its potential prognostic value for cardiovascular outcomes. Following PRISMA extension for scoping reviews guidelines, literature was systematically searched in Embase, PubMed, Scopus, Web of Science, and CINAHL. Relevant clinical trials, observational studies, cohort studies, cross-sectional studies, and systematic reviews published in English were screened. Of 369 articles identified, 17 articles were included. Studies differed in the BP targets used (e.g., BP < 140/90 mmHg or 130/80 mmHg; systolic BP within 110-130 mmHg or 120-140 mmHg), BP-TTR measurement duration (range 24 h to 15 years), and calculation method (linear interpolation method, n = 12 [71%]; proportion of BP readings at target, n = 5 [29%]). Regardless of method, studies consistently demonstrated that higher BP-TTR was associated with reduced risk of cardiovascular outcomes. Six of eight studies found the association was independent of mean achieved BP or last measured BP. Despite variation in methods of BP-TTR determination, these studies demonstrated the potential prognostic value of BP-TTR for cardiovascular outcomes beyond current BP control measures. We recommend standardization of BP-TTR methodology, with preference for linear interpolation method when BP measurements are few or less frequent, and proportion of BP readings method when large number of BP readings are available.

Updates on Topical Dyad and Triple Combination Therapies Approved for Acne Vulgaris.

Acne vulgaris is a multifaceted disease characterized by inflammatory and noninflammatory lesions. Topical combination therapies offer a multifaceted approach to acne treatment, with synergistic effects and a broad spectrum of action against multiple factors in acne pathogenesis in one single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene, a combination therapy consisting of clindamycin phosphate 1.2%, benzoyl peroxide (BPO) 3.1%, and adapalene 0.15%, is a novel treatment, the only FDA-approved triple combination drug that offers effective treatment of acne vulgaris. This review aims to provide information on clindamycin phosphate/benzoyl peroxide/adapalene and review the literature on combination topical acne medications approved in the United States. This search was conducted on topical combination therapies for acne, their efficacy, adverse effects, and impacts on quality of life with a specific focus on the newly approved clindamycin phosphate/benzoyl peroxide/adapalene and its sub-component dyads, along with other combinations. PubMed, SCOPUS, Embase, Cochrane, and Web of Science databases were searched for publications in 2018-2023. Primary sources were given priority, and secondary sources such as other reviews were considered to supplement any missing information. It was found that various topical dyad and triad combinations exist for acne vulgaris, including adapalene/BPO, tazarotene/clindamycin, clindamycin/BPO, adapalene/clindamycin, topical tretinoin/azelaic acid, topical tretinoin/BPO, and clindamycin phosphate/benzoyl peroxide/adapalene. Dyad and triple combinations represent a promising, convenient solution for acne management, potentially improving patient adherence due to its single formulation. Clindamycin phosphate/benzoyl peroxide/adapalene exhibited significantly high efficacy in treating both inflammatory and noninflammatory lesions, a minimal side effect profile, although no significant changes in quality-of-life measures. Further research is indicated to assess its long-term efficacy and impact on other acne metrics such as cost, scarring, psychosocial implications, and impact on diverse patient populations.

Evaluating the clinical efficacy of pulsed dye laser with sirolimus for treatment of capillary malformations: A systematic review.

Port-wine stains (PWS) are capillary vascular anomalies that are often treated with pulsed-dye laser (PDL). Revascularization limits persistent clearance; however, the anti-angiogenic effects of sirolimus (SIRO) may inhibit revascularization. This review aims to determine differences in PWS outcomes when treated with PDL monotherapy or in combination with SIRO. A systematic review was conducted using PubMed, Cochrane, and Embase databases. The following search terms were used: 'port wine stain PDL SIRO', 'port wine stain PDL', and 'port wine stain PDL and topical treatment' with (MeSH) and (Title/Abstract) limits. The search was limited to the English language and human-subject studies conducted between 1 January 2000 and 1 June 2023. Inclusion criteria included studies evaluating SIRO as an adjunct to PDL in patients with PWS. Data extraction and quality assessment were performed by two independent reviewers. A total of nine studies met the inclusion criteria, which included randomized controlled trials (3), case series (2), case reports (3), and a prospective intrapatient study (1), which represented a total of 58 patients. Five studies showed improvement of a measured post-treatment PDL parameter including shortening treatment time and less frequent dosing. A subset of studies (4/9) which did not demonstrate significant clinical improvements exhibited significant photographic evidence of improvement. Heterogeneity among the studies highlights the need for further research and standardization. While adjunctive SIRO shows promise, larger studies and comprehensive evaluation methods are required to establish conclusive safety and efficacy guidelines to shape clinical decision-making.