Summary Peripheral vascular malformations (VMs) are birthmarks or swellings caused by the faulty development of blood vessels in the embryo. Different types are classified according to whether the components are mainly lymph vessels (LMs), veins (VMs) or combined arteries and veins (AVMs). It is hard to assess the various medical and surgical treatments available because there are no agreed methods for measuring the outcome. This international group carried out an on‐line survey of health professionals and patients to decide which factors would be important to record in future clinical trials. First they listed aspects of the condition and its treatment in 36 domains covering 97 specific items. Then they asked 167 doctors and 134 patients and parents of patients to score the domains from 0 (not important) to 4 (crucial). The options were progressively narrowed down over 3 rounds of the survey and a consensus conference. The finally agreed “core outcome set” covered: scan results, doctors’ assessment of problems caused by pressure from the VM, patient or parent's assessments of symptoms, pain and quality of life, and their satisfaction with the treatment, outcome and any adverse effects. Additional specific factors for LMs were infections and lymphatic fluid leakage, for VMs thrombosis and for AVMs heart function and bleeding. Recurrence after treatment and appearance were also recommended for inclusion. This international consensus establishes what factors should be assessed in future trials of treatments for vascular malformations, but further work is required to decide exactly how they should be measured and reported.

For the past two decades much research on selective photothermolysis of port wine stain vasculature has been devoted to optimizing laser parameters. Unfortunately, 60% of patients still respond suboptimally to laser therapy, despite significant innovations in treatment strategies and laser technology. Here we present a novel treatment approach based on combining selective photothermolysis with the administration of prothrombotic and/or anti-fibrinolytic pharmaceutical agents, with the aim of enhancing vaso-occlusion and post-treatment remodelling in difficult-to-target vessels. A hypercoagulable state of blood will instill laser-induced occlusive thrombosis in a wider array of vessel diameters at greater dermal depths, whereby larger vascular segments will ultimately undergo the chronic inflammatory processes that result in blood volume reduction, and thus lesional blanching. With thrombosis as a primary trigger for these inflammatory processes, we have extrapolated the threshold damage profile that is required for clinically relevant thrombus formation. Consequently, a recently proposed model of thrombus organization, in which recanalization is associated with endothelial progenitor cell-mediated neovasculogenesis, is elaborated in the framework of lesional blanching and juxtaposed to angiogenic reconstruction of affected dermal vasculature. Since neovasculogenesis and angiogenesis are regulated by the degree of vaso-occlusion and corollary drop in local oxygen tension, both can be manipulated by the administration of procoagulant pharmaceuticals. Lastly, in an effort to optimally balance selective photothermolysis with pharmacokinetics and clinical safety, the use of a gold nanoshell drug delivery system, in which the procoagulant drugs are encapsulated by a wavelength-modulated, gold-coated polymer matrix, is proposed. We have termed this modality site-specific pharmaco-laser therapy.

No abstract

Background Capillary malformations of the head and neck region often cause psychological and physical burden. As the effectiveness of modern laser and light therapies is still suboptimal, patients often seek different therapeutic strategies. Other recognized, but not routinely proposed therapies include cosmetic camouflage, surgery, and medical tattooing. Information on therapeutic outcomes is currently lacking for patients to adequately participate in the treatment decision-making process. Objective The objective of this systematic review was to review the effectiveness and safety of recognized therapies for untreated capillary malformations of the head and neck: laser and light treatment modalities, photodynamic therapy, cosmetic camouflage, medical tattooing, and surgery. Methods PubMed, Embase, and the Cochrane Central Register of Controlled Trials were searched up to 16 December, 2020 for observational and experimental studies examining recognized therapies for untreated capillary malformations of the head and neck. Two reviewers independently evaluated the risk of bias of included studies. Predefined treatment and safety outcomes of pooled data were scored using the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results We included 48 observational and three randomized studies (totaling 3068 patients), evaluating nine different therapies. No studies on surgery or cosmetic camouflage matched our inclusion criteria. The pooled proportion of patients reaching a ≥75% clearance was 43% (95% confidence interval 24-64%; I 2 = 55%) for the pulsed dye laser after three to eight treatment sessions (GRADE score: very low). Other therapies were less effective. Hyperpigmentation was most frequently described after the pulsed dye laser (incidences up to 40%). Pain was most common after photodynamic therapy, yet the intensity was unreported. Substantial heterogeneity among studies as to patient characteristics and outcomes limited pooling and data comparisons. Conclusions The pulsed dye laser seems preferable for treatment-naive capillary malformations of the head and neck region, yet demonstrates greater hyperpigmentation rates compared with other therapies. Our results are, however, based on lowquality evidence. Future studies using uniform outcome measures and validated metrics are warranted for study comparability. Based on this systematic review, clinicians and patients should be aware of the limited evidence about the available options when making (shared) treatment decisions for capillary malformations. Trial Registration Review registration number PROSPERO database: CRD42020199445. Gonca Cinkara and Ginger Beau Langbroek contributed equally to this review.

No abstract