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Background: Evidence-based guidelines for the treatment of vascular malformations (VMs) are not readily available, possibly due to the diversity in methods used to evaluate treatment efficacy in clinical research, complicating the aggregation and comparison of study results. The Outcome measures for VAscular MAlformations (OVAMA) questionnaire was developed to measure uniformly symptoms and appearance (i.e. condition-specific core outcome domains) in patients with VMs. However, the OVAMA questionnaire needs to be responsive to changes in these constructs in order to assess whether disease status has changed since treatment., Objectives: To assess the responsiveness of the OVAMA questionnaire in patients with VMs., Methods: In a prospective longitudinal study, patients completed the OVAMA questionnaire at baseline and at 8 weeks after treatment or a watchful waiting policy. Additionally, patients completed global rating of change (GRC) scales at follow-up. Responsiveness was evaluated following the criterion approach of testing predefined hypotheses about expected relationships between the OVAMA questionnaire and GRC scales measuring the same constructs. The OVAMA questionnaire was considered responsive if ≥ 75% of the hypotheses were confirmed., Results: Between July 2020 and September 2022, 89 patients were recruited in a vascular anomaly centre in the Netherlands; 63 patients completed the questionnaires at baseline and follow-up. In total, 15 constructs of the OVAMA questionnaire were assessed for 5 hypotheses. Of these 75 hypotheses, 63 (84%) were confirmed, providing evidence that the OVAMA questionnaire is responsive to change., Conclusion: Our study found convincing evidence that the OVAMA questionnaire is responsive to changes in symptoms and appearance in patients with VMs. In addition to determining a baseline for symptoms and appearance, the OVAMA questionnaire can now be used to evaluate the effect of treatment from a patient's perspective. The responsive OVAMA questionnaire allows for uniform evaluation and comparison of the effects of treatment on the condition-specific core outcome domains, tackling heterogeneity in outcome measurement and improving the clinical research of VMs., Competing Interests: Conflicts of interest P.I.S. has received departmental independent research grants for the TREAT NL registry from pharma since December 2019; is involved in performing clinical trials with many pharmaceutical industries that manufacture drugs used for the treatment of, for example, psoriasis and atopic dermatitis, for which financial compensation is paid to the department/hospital; and is Chief Investigator of the systemic and phototherapy atopic eczema registry (TREAT NL) for adults and children. P.I.S. was involved in the development of one of the Harmonizing Outcome Measures for Eczema (HOME) core outcome instruments [Recap of atopic eczema (RECAP)] and in the development of the Outcome measures for VAscular MAlformations (OVAMA) questionnaire for vascular malformations., (© The Author(s) 2024. Published by Oxford University Press on behalf of British Association of Dermatologists.)

Vascular malformations (VMs) are clinically diverse with regard to the vessel type, anatomical location, tissue involvement and size. Consequently, symptoms and disease impact differ significantly. Diverse causative mutations in more and more genes are discovered and play a major role in the development of VMs. However, the relationship between the underlying causative mutations and the highly variable phenotype of VMs is not yet fully understood. In this systematic review, we aimed to provide an overview of known causative mutations in genes in VMs and discuss associations between the causative mutations and clinical phenotypes. PubMed and EMBASE libraries were systematically searched on November 9th, 2022 for randomized controlled trials and observational studies reporting causative mutations in at least five patients with peripheral venous, lymphatic, arteriovenous and combined malformations. Study quality was assessed with the Newcastle-Ottawa Scale. Data were extracted on patient and VM characteristics, molecular sequencing method and results of molecular analysis. In total, 5667 articles were found of which 69 studies were included, reporting molecular analysis in a total of 4261 patients and 1686 (40%) patients with peripheral VMs a causative mutation was detected. In conclusion, this systematic review provides a comprehensive overview of causative germline and somatic mutations in various genes and associated phenotypes in peripheral VMs. With these findings, we attempt to better understand how the underlying causative mutations in various genes contribute to the highly variable clinical characteristics of VMs. Our study shows that some causative mutations lead to a uniform phenotype, while other causal variants lead to more varying phenotypes. By contrast, distinct causative mutations may lead to similar phenotypes and result in almost indistinguishable VMs. VMs are currently classified based on clinical and histopathology features, however, the findings of this systematic review suggest a larger role for genotype in current diagnostics and classification., (© 2023 The Authors. Journal of the European Academy of Dermatology and Venereology published by John Wiley & Sons Ltd on behalf of European Academy of Dermatology and Venereology.)

Background: Discrepancies have been noted between the clinical and histologic diagnosis of vascular malformations., Objective: To evaluate the effectiveness of the International Society for Study of Vascular Anomalies (ISSVA) classification in diagnosing benign vascular anomalies based on clinical and (immuno) histologic parameters, focusing on lymphatic differentiation and vascular proliferation., Method: A retrospective study of 121 consecutive patients with benign skin and soft-tissue vascular anomalies located in the head and neck region (pyogenic granulomas and angioma senilis were excluded) by applying multiplex immunohistochemistry staining for lymph vessels (D2-40), endothelial blood vessels, and proliferating cells (Ki67). Clinical and histologic diagnosis was revised after the ISSVA classification., Results: Initially, 64 lesions were diagnosed as tumors and 57 as malformations. Revision diagnosis following the ISSVA classification revealed 27 tumors, 90 malformations (22.2% lymphatic), and 4 non-ISSVA. Immunostaining showed lymphatic differentiation in 24 (19.8%) of 121 cases, of which 20 were malformations. Proliferative activity (Ki67+) was found in 41 (33.8%) of 121 cases, of which 8 were arteriovenous malformations., Limitation: Quality and size of materials (biopsies vs resections) and clinical information., Conclusion: The diagnostic accuracy of combined histologic and clinical approaches for identifying vascular anomalies following the ISSVA classification can be substantially enhanced by incorporating additional immunostaining techniques to evaluate lymphatic differentiation and proliferative activity, particularly in identifying the occurrence of vascular malformations., Competing Interests: None disclosed., (© 2023 by the American Academy of Dermatology, Inc. Published by Elsevier Inc.)

Background: Madelung deformity is a rare congenital hand difference with little known regarding the patient perspective. In this cross-sectional survey study, we harnessed the global reach of social media to understand the clinical spectrum of Madelung deformity and its impact on physical, mental, and social health., Methods: A survey was developed based on a previously published protocol and multiple Patient-Reported Outcomes Measurement Information System (PROMIS) short forms. The survey was distributed on several Madelung deformity communities on Facebook and Instagram. T -scores were calculated, interpreted, and compared between patients who underwent surgery and those who did not. Correlations between scores were calculated using the Spearman rank correlation coefficient., Results: Mean PROMIS scores for adults were as follows: pain intensity, 4.9 ± 2.8; pain interference, 57.6 ± 10.0; upper extremity, 35.2 ± 8.1; depression, 53.8 ± 11.1; anxiety, 55.4 ± 11.4; and ability to participate in social roles and activities, 42.5 ± 7.7. Mean scores for children were as follows: pain intensity, 5.0 ± 2.8; pain interference, 55.7 ± 11.3; upper extremity function, 24.6 ± 10.4; depressive symptoms, 57.7 ± 11.3; anxiety, 57.3 ± 11.9; and peer relationships, 42.2 ± 10.3., Conclusions: Madelung deformity has significant effects on patients' physical, mental, and social well-being, even after surgical treatment. Using social media, we were able to compensate for Madelung deformity's rarity by engaging an international audience, demonstrating the feasibility to conduct research through it, and providing a global perspective of the disease entity.

Background: Treatment indications of congenital melanocytic naevi (CMN) have shifted from the prevention of malignant transformation more towards the improvement of appearance and psychosocial health. Surgical excision is often preferred, but its safety and effectiveness remain unclear., Objective: To assess the outcomes of surgical excision of medium-to-giant CMN., Primary Outcome: safety (complications)., Secondary Outcome: effectiveness (satisfaction and CMN core outcomes)., Methods: PubMed, EMBASE, and CENTRAL were searched for studies on the excision of medium-to-giant CMN and/or CMN requiring reconstruction or serial excision. Meta-analyses of safety per patient were conducted, and pooled outcomes of safety and effectiveness were presented in summary-of-findings tables., Results: A total of 1444 studies were found, of which 22 were included, evaluating 643 eligible patients. Study quality varied, and reporting of baseline characteristics and outcomes was heterogeneous. Pooled proportions were overall 9.8% for major wound-related complications, 1.2% for minor wound-related complications, 1.2% for scar-related complications, and 4.3% for anatomical deformities. For large/giant CMN, complication rates were, respectively, 23.1%, 2.9%, 12.9%, and 2.4%; and for CMN with eyelid involvement, 0.5%, 3.3%, 0.4%, and 54.2%. Patients rated their satisfaction with the cosmetic outcome as 24.4% excellent, 71.0% good, and 4.6% poor/moderate. Physicians rated this as 18.3% excellent, 70.1% good, and 11.7% poor/moderate. Thirty-five other outcomes of effectiveness were summarized. However, many were rarely reported., Conclusions: Surgical excision of CMN appears to be safe and effective in many cases, depending on CMN size and location. Major wound-related complications and scar-related complications occurred more frequently with large/giant CMN, whereas anatomical deformities occurred with the majority of CMN with eyelid involvement., Competing Interests: Declaration of Competing Interest None., (Copyright © 2022 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Peripheral vascular malformations (VMs) may lead to disfigurement of the body and face, potentially impairing aesthetic appearance. Yet, data on appearance in this population is limited. This study aimed to examine appearance-related concerns and their impact on health-related quality of life (HR-QoL) in patients with VMs., Methods: In this cross-sectional study, 384 adults and 194 children with VMs were invited to complete the Outcome Measures for VAscular MAlformations (OVAMA) questionnaire to evaluate potential appearance-related concerns on a five-point verbal-rating scale, with higher scores indicating more appearance-related concerns (e.g., colour-difference, facial-distortion, reduced self-esteem, and dissatisfaction with appearance). HR-QoL was evaluated using Patient-Reported Outcome Measurement Information System (PROMIS). Subgroups of patients reporting more appearance-related concerns were identified using univariate analysis. Associations between appearance-related concerns and various HR-QoL domains (e.g., anxiety and social participation) were assessed., Results: A total of 184 patients (32%) completed the questionnaires; 121 patients (66%) reported that one or more appearance outcome was severely affected (i.e., 4-5 out of 5). The following factors statistically significant associated with more appearance-related concerns: capillary/combined origin, facial localization, subcutaneous tissue involvement, larger size, overgrowth, and diagnosis of a syndrome. In adults, dissatisfaction with appearance and reduced self-esteem due to the appearance of the VM correlated with more anxiety and depression symptoms. Reduced self-esteem correlated with less social participation. In children, bodily distortion and being stared at were correlated with less peer relationships., Conclusion: Severe appearance-related concerns were present in two-thirds of patients with VMs, impairing their mental HR-QoL. Clinicians should acknowledge appearance-related aspects, monitor psychological well-being, and offer intervention aimed at improving satisfaction with appearance., Competing Interests: Declaration of Competing Interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Introduction: Vascular malformations of the upper extremity are uncommon, and there is great heterogeneity in their occurrence and appearance. There is no golden standard for the treatment of vascular malformations of the upper extremity and limited evidence on this subject has been published., Objective: This review aims to answer the question whether surgical treatment leads to less recurrence and complications than non-surgical treatment for patients with vascular malformations of the upper extremity., Materials and Methods: A literature search in PubMed was performed up to September 2019 by using the following terms: vascular malformation, upper extremity and surgery. Inclusion criteria were: a mean follow-up duration of at least 12 months [1], outcome measurements including recurrences and/or complications [2] and the involvement of patients with vascular malformations of the upper extremity [3]., Results: In total, 883 articles were found, of which seven were included in this review. A total of 358 patients were included in these studies, including 208 patients with upper extremity vascular malformations. Minor surgical complications were seen in 20% of the cases, and major complications occurred in 6%. Recurrence was reported in 32% of the cases., Conclusion: Surgery for vascular malformations of the upper extremity can be a safe and effective treatment option, although some cases are better off when treated non-surgically. Literature shows various complication rates for non-surgical treatment of upper extremity vascular malformations. To determine in which case surgery is the better option, we should identify factors leading to surgical complications., Competing Interests: None., (© 2022 The Authors.)

Objective: Vascular malformations (VM) can negatively impact the patient's quality of life (QoL). Pain is a common problem in these patients. The aim of this study was to investigate risk factors associated with pain and to assess how pain affects QoL., Methods: This prospective cross-sectional study was conducted in a tertiary vascular anomaly expertise center. Between June and December 2020, all patients from our local database (334 adults and 189 children) with peripheral VMs were invited to complete the Outcome Measures for VAscular MAlformations questionnaire to evaluate the presence, frequency, and intensity of pain. Additionally, patients were asked to complete several Patient-Reported Outcome Measurement Information System scales to evaluate their QoL. Risk factors associated with pain were identified in bivariate analysis and multivariable logistic regression. QoL domains were compared between patients who experienced pain and patients who did not., Results: A total of 164 patients completed the questionnaire about pain and 133 patients completed all QoL questionnaires. Approximately one-half of the patients (52%) reported pain in the past four weeks and 57% of these patients reported pain daily or several times a week. Female sex (P = .009), lesions located in the upper extremity (P < .001) or lower extremity (P < .001), and intramuscular/intraosseous lesions (P = .004) were independently associated with the presence of pain. The following QoL domains were diminished in patients who experienced pain in comparison with patients who did not: pain interference (P < .001), physical functioning (P < .001), and social participation (P < .001) in adults, and pain interference (P = .001), mobility (P = .001), and anxiety (P = .024) in children., Conclusions: Pain is a frequently reported complaint in patients with VMs and is present in approximately one-half of the patients. Patients with lesions located in the upper or lower extremity, intramuscular/intraosseous lesions, and female patients are more likely to experience pain. The presence of pain negatively impacted patients' QoL. Although VM are a benign condition and expectative management is frequently applied, our study shows that pain is a serious concern and needs to be actively assessed. Pain is a sign of various etiologies and should be examined to properly treat the pain., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Macrodactyly is a rare congenital disorder of overgrowth affecting the digits of the upper or lower extremity. Mostly, patients are surgically treated during childhood to reduce the digit or to stop growth. There are no standardized guidelines for the treatment and follow-up of macrodactyly. Consequently, follow-up may not be regularly scheduled into adulthood., Methods: A retrospective, descriptive analysis of patients with the long-term progression of macrodactyly who presented at our tertiary referral hospital between July 2018 and March 2020 was performed. All patients from our local macrodactyly database were screened for progression of macrodactyly since adulthood; this resulted in four patients. The aim of these case series is to highlight the clinical features and disease course at long-term follow-up., Results: All patients were surgically treated during childhood and showed progression of tissue overgrowth during adult life. All patients developed severe secondary degenerative bone changes in macrodactyly affected digits, such as ankyloses of joints, new bone formation, and bony spurs. Subsequently, tissue overgrowth and degenerative bone changes led to functional problems., Conclusion: Patients with macrodactyly may experience growth during adult life, which may progress to deforming changes. Consequently, patients should be informed about the possible growth, and the progressive growth should be monitored., (© 2021 The Author(s).)

Background: The symptoms and appearance of vascular malformations can severely harm a patient's quality of life. The aim of treatment of vascular malformations generally is to improve condition-specific symptoms and/or appearance. Therefore, it is highly important to start testing treatment effects in clinical studies from the patient's perspective., Objectives: To develop a patient-reported outcome measure for measuring symptoms and appearance in patients with vascular malformations., Methods: A first draft of the patient-reported outcome measure was based on the previously internationally developed core outcome set. The qualitative part of this study involved interviews with 14 patients, which led to a second draft. The second draft was field tested cross-sectionally, after which groups of items were evaluated for adequate internal consistency (Cronbach's alpha > 0·7) to form composite scores. Construct validity was evaluated by testing 13 predefined hypotheses on known-group differences., Results: The patient interviews ensured adequate content validity and resulted in a general symptom scale with six items, a head and neck symptom scale with eight items, and an appearance scale with nine items. Cronbach's alpha was adequate for two composite scores: a general symptom score (0·88) and an appearance score (0·85). Ten out of 13 hypotheses on known-group differences were confirmed, confirming adequate construct validity., Conclusions: With the development of the OVAMA questionnaire, outcomes of patients with vascular malformations can now be evaluated from the patient's perspective. This may help improve the development of evidence-based treatments and the overall care for patients with vascular malformations., (© 2021 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Surgical treatment of peripheral vascular malformations is widely performed as primary and secondary treatments. Excellent results have been reported; however, it is thought that complications are likely to occur because of damage to adjacent structures. This systematic review aimed to elucidate the indications and outcomes of surgical treatment of vascular malformations., Methods: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials were searched for studies reporting outcomes of surgery in at least 15 patients with a single type of peripheral soft-tissue vascular malformation. The authors extracted data on patient and lesion characteristics, treatment characteristics, and outcomes (including complications). Meta-analysis was conducted on recurrence and complication rates., Results: A total of 3042 articles were found, of which 24 were included: nine studies on arteriovenous malformations, seven on venous malformations, and eight on lymphatic malformations, totaling 980 patients. Meta-analyses showed pooled proportions for recurrences of 11 percent in arteriovenous malformations, 5 percent in venous malformations, and 9 percent in lymphatic malformations. Pooled proportions of major complications were 9 percent for arteriovenous malformations, 3 percent for venous malformations, and 1 percent for lymphatic malformations. The authors found a 5 percent pooled recurrence proportion in total resections, compared with 28 percent in subtotal resections. The pooled odds ratio for recurrence in total and subtotal resections showed a significant lower recurrence rate after total resection (odds ratio, 0.14, p = 0.02)., Conclusions: Surgical treatment of vascular malformations appears to be effective and safe in many cases. However, it seems that surgery is performed predominantly in small lesions, and subtotal resection has a higher risk of recurrence than total resection., (Copyright © 2021 by the American Society of Plastic Surgeons.)

Background: The OVAMA ( O utcome M easures for VA scular MA lformations) project determined quality of life (QoL) as a core outcome domain for evaluating treatment effect in vascular malformations. To correctly evaluate treatment effect on QoL, patient-reported outcome measures (PROMs) are needed that are responsive to changes. In children with vascular malformations, we explored if two widely used PROMs were responsive to changes: the Pediatric Quality of Life Inventory (PedsQL) and the Children's Dermatology Life Quality Index (CDLQI)., Methods: In an international multicenter prospective study, conservatively and invasively treated children completed the PedsQL and CDLQI at baseline and after follow-up of 6-8 weeks. At follow-up, change in health was assessed by a global rating of change (GRC) scale. Responsiveness was assessed by testing hypotheses on expected correlation strength between change scores of the PROMs and the GRC scale, and by calculating the area under the receiver operating characteristics curve (AUC). The PROMs were considered responsive if ≥75% of the hypotheses were confirmed or if the AUC was ≥0.7., Results: Twenty-nine children were recruited in three centers in the Netherlands and United States, of which 25 completed all baseline and follow-up measurements. For both the PedsQL and CDLQI, less than 75% of the hypotheses were confirmed and the AUC was <0.7., Discussion: The results suggest that these PROMs are not sufficiently responsive for evaluating treatment effect in peripheral vascular malformations. Our study emphasizes the need for assessing responsiveness before using a PROM in evaluating treatment effect., Competing Interests: None., (© 2020 The Author(s).)

Background: The OVAMA (Outcome Measures for Vascular Malformations) project determined quality of life (QoL) as a core outcome domain for patients with vascular malformations. In order to measure how current therapeutic strategies alter QoL in these patients, a patient-reported outcome measurement (PROM) responsive to changes in QoL is required., Objectives: To assess the responsiveness of two widely used generic QoL PROMs, the Medical Outcomes Study Short Form 36 (SF-36) and Skindex-29, in adult patients with vascular malformations., Methods: In an international multicentre prospective study, treated and untreated patients completed the SF-36 and Skindex-29 at baseline and after a follow-up period of 6-8 weeks. Global rating of change (GRC) scales assessing various QoL-related outcome domains were additionally completed. Per subscale, responsiveness was assessed using two methods: by testing hypotheses on expected correlation strength between change scores of the questionnaires and the GRC scales, and by calculating the area under the receiver operating characteristics curve (AUC). The questionnaires were considered responsive if ≥ 75% of the hypotheses were confirmed or if the AUC was ≥ 0·7., Results: Eighty-nine participants were recruited in three centres in the Netherlands and the U.S.A., of whom 67 completed all baseline and follow-up questionnaires. For all subscales of the SF-36 and Skindex-29, < 75% of the hypotheses were confirmed and the AUC was < 0·7., Conclusions: Our findings suggest that the SF-36 and Skindex-29 seemed unresponsive to change in QoL. This suggests that alternative PROMs are needed to measure - and ultimately improve - QoL in patients with vascular malformations. What's already known about this topic? Quality of life is often impaired in patients with vascular malformations. Quality of life is considered a core outcome domain for evaluating treatment of vascular malformations. To measure the effect of treatment on quality of life, a patient-reported outcome measure is required that is responsive to changes in quality of life. What does this study add? This is the first study assessing the responsiveness of quality-of-life measures in patients with vascular malformations. The results seem to indicate that the Medical Outcomes Study Short Form 36 (SF-36) and Skindex-29 are not responsive to changes in quality of life in patients with vascular malformations. What are the clinical implications of this work? Medical Outcomes Study Short Form 36 (SF-36) and Skindex-29 are not ideal to assess the effect on quality of life over time, of treatment strategies for peripheral vascular malformations., (© 2019 The Authors. British Journal of Dermatology published by John Wiley & Sons Ltd on behalf of British Association of Dermatologists.)

Background: Sclerotherapy has become the gold standard for the first-line therapy of most venous (VMs) and lymphatic malformations (LMs) of the head and neck. Numerous sclerosing agents are used to treat these low-flow vascular malformations; however, to date, it remains unclear which sclerosing agent is superior in terms of effectiveness and safety., Methods: In a systematic review of the literature (1995-present), we compare the effectiveness and complications of the sclerosing agents most commonly used for cervicocraniofacial VMs and LMs., Results: The literature search yielded 1155 articles, among which 36 (1552 patients) were included in the systematic review. The quality of evidence was low. Pingyangmycin, absolute ethanol, OK-432, ethanolamine oleate, bleomycin, polidocanol, doxycycline, and sodium tetradecyl sulfate (STS) were the most reported sclerosing agents. All agents seem effective, and the mean overall response varies from 71% to 100%. Complications occurred more frequently after ethanol sclerotherapy (18%), compared to other sclerosing agents (0-6%). Cellulitis and ulceration were encountered following sclerotherapy with most sclerosing agents, but skin necrosis was particularly observed after ethanol. Facial nerve paralysis occurred only after OK-432 (0.05%) and ethanol sclerotherapy (6%)., Conclusions: This systematic review could not identify a significantly superior sclerosing agent in terms of effectiveness, due to the low quality of the available evidence. Until stronger evidence is available, the difference in complication rates is potentially the deciding factor in the choice between sclerosing agents. As a significantly higher complication rate and more severe local complications were encountered after using absolute ethanol, we cannot recommend this agent for sclerotherapy of cervicofacial vascular malformations., (Copyright © 2015 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)