Therapeutic Strategies for Untreated Capillary Malformations of the Head and Neck Region: A Systematic Review and Meta-Analyses

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.

A core outcome domain set for clinical research on capillary malformations (the COSCAM project): an e-Delphi process and consensus meeting

“…However, in our CDS no adverse events (AEs) are included. This may be due to the fact that AEs are not that common post (laser) therapy and were possibly not found important enough to be measured in all future clinical trials on CMs 13 . Yet, our core outcome subdomains are the minimum set that should be measured in clinical trials on therapies.…”

“…This may be due to the fact that adverse events are not that common after (laser) therapy and were possibly not deemed important enough to be measured in all future clinical trials on CMs. 13 Yet, our core outcome subdomains are the minimum set that should be measured in clinical trials on therapies. Researchers are free to measure additional outcomes, such as adverse events, that may be important depending on the study objective and type of treatment.…”

“…Currently, there is no consensus on which outcomes should be measured when evaluating treatment results 20 . This hampers the evaluation and comparison of treatment modalities and, as a result, there is limited evidence available on the best treatment options 13 . A core outcome set (COS) facilitates standard reporting of trial outcomes and, by including patients in the development process, incorporates patient‐relevant outcomes.…”

“… 20 This hampers the evaluation and comparison of treatment modalities and, as a result, there is limited evidence available on the best treatment options. 13 A core outcome set (COS) facilitates standard reporting of trial outcomes and, by including patients in the development process, incorporates patient‐relevant outcomes. A COS, containing a core outcome domain set (CDS) and a core outcome measurement set, includes a minimum set of outcomes that should be measured and reported in clinical research when studying a specific health condition.…”

“…Multiple therapeutic strategies are available, including cosmetic camouflage, medical tattooing, surgical excision, and laser and light therapies 13 . Even though pulsed‐dye laser is still the treatment of choice, its effectiveness in terms of clearance rate has barely improved over the last three decades 14 .…”