The biodistribution of triamcinolone acetonide injections in severe keloids: an exploratory three-dimensional fluorescent cryomicrotome study.

Intralesional corticosteroid injections are a first-line treatment for keloids; yet clinical treatment results are highly variable and often suboptimal. Variation in triamcinolone acetonide (TAC) biodistribution may be an important reason for the variable effects of TAC treatment in keloids. In this exploratory study we investigated the biodistribution of TAC in keloids and normal skin using different drug delivery techniques. Fluorescent-labeled TAC suspension was administered into keloids and normal skin with a hypodermic needle and an electronic pneumatic jet injector. TAC biodistribution was represented by the fluorescent TAC volume and 3D biodistribution shape of TAC, using a 3D-Fluorescence-Imaging Cryomicrotome System. Twenty-one keloid and nine normal skin samples were analyzed. With needle injections, the mean fluorescent TAC volumes were 990 µl ± 479 in keloids and 872 µl ± 227 in normal skin. With the jet injector, the mean fluorescent TAC volumes were 401 µl ± 252 in keloids and 249 µl ± 67 in normal skin. 3D biodistribution shapes of TAC were highly variable in keloids and normal skin. In conclusion, TAC biodistribution in keloids is highly variable for both needle and jet injection. This may partly explain the variable treatment effects of intralesional TAC in keloids. Future research is needed to confirm this preliminary finding and to optimize drug delivery in keloids.

Effect of Keloid Properties on Treatment Efficacy, a Systematic Review.

BACKGROUND: The efficacy of keloid treatment in randomized studies is highly variable. However, no systematic review has been performed to evaluate the effect of different keloid properties on treatment efficacy. OBJECTIVE: To identify clinically relevant keloid properties that may influence treatment efficacy. MATERIALS AND METHODS: An electronic database search was conducted. Two reviewers independently selected randomized controlled trials (RCTs) and performed a methodologic quality assessment using the Cochrane risk-of-bias 2.0 tool. RESULTS: One thousand five hundred twenty studies were screened, and 16 RCTs, involving 1,113 patients, were included. The authors found lower efficacy in older keloids ( n = 3), keloids located on the chest, extremities, pinna, and shoulder ( n = 3), larger keloids ( n = 2), lower baseline Vancouver Scar Scale score ( n = 1), and keloids with history of recurrence ( n = 1). Overall, most studies had a high risk of bias. CONCLUSION: Only a minority of studies specifically addressed keloid properties, which makes comparisons between studies challenging. The authors' results suggest that keloid location, duration prior to treatment, size, history of recurrence, and severity are clinically relevant keloid properties that affect treatment efficacy. Further studies are crucial to corroborate the authors' findings, establish a clinically relevant keloid classification, and ultimately develop an evidence-based treatment algorithm that takes these properties into account.

Current Practice in Keloid Treatment: a Survey of Dutch Dermatologists and Plastic Surgeons.

BACKGROUND: Several therapeutic options are available for the treatment of keloids, but it remains unclear which treatment options are most commonly used by practitioners. OBJECTIVE: To explore the prevailing treatment for different keloid phenotypes among dermatologists and plastic surgeons in the Netherlands. METHODS: Members of the Dutch society for Plastic surgery and the Dutch society for Dermatology and Venereology were asked to participate. Questions elaborated on the treatment for a small and a large keloid on the mandibula and multiple keloids on the chest. RESULTS: One hundred forty-three responses were obtained. Heterogeneity in treatment was extremely high for the small, large, and multiple keloids with 27, 35, and 33 various first choices, respectively. Intralesional corticosteroids were most often chosen for all 3 different keloid phenotypes. These were mostly (61%) administered as monotherapy for the small keloid and mostly combined with other treatments for the large keloid (19%) and multiple keloids (43%). Surgery was chosen regularly (22%) for the large keloid, mostly combined with intralesional corticosteroids (10%) or brachytherapy (8.4%). CONCLUSION: Keloid treatment is very heterogeneous among dermatologists and plastic surgeons, even in a relatively small country as the Netherlands. Moreover, the treatment choice depends on the keloid phenotype.

Baker Grade IV Capsular Contracture Is Correlated with an Increased Amount of Silicone Material: An Intrapatient Study.

BACKGROUND: Breast implant surgery is one of the most frequently performed procedures by plastic surgeons worldwide. However, the relationship between silicone leakage and the most common complication, capsular contracture, is far from understood. This study aimed to compare Baker grade I with Baker grade IV capsules regarding their silicone content in an intradonor setting, using two previously validated imaging techniques. METHODS: Twenty-two donor-matched capsules from 11 patients experiencing unilateral complaints were included after bilateral explantation surgery. All capsules were examined using both stimulated Raman scattering (SRS) imaging and staining with modified oil red O (MORO). Evaluation was done visually for qualitative and semiquantitative assessment and automated for quantitative analysis. RESULTS: Using both SRS and MORO techniques, silicone was found in more Baker grade IV capsules (eight of 11 and 11 of 11, respectively) than in Baker grade I capsules (three of 11 and five of 11, respectively). Baker grade IV capsules also showed significantly more silicone content compared with the Baker grade I capsules. This was true for semiquantitative assessment for both SRS and MORO techniques ( P = 0.019 and P = 0.006, respectively), whereas quantitative analysis proved to be significant for MORO alone ( P = 0.026 versus P = 0.248 for SRS, respectively). CONCLUSIONS: In this study, a significant correlation between capsule silicone content and capsular contracture is shown. An extensive and continued foreign body response to silicone particles is likely to be responsible. Considering the widespread use of silicone breast implants, these results affect many women worldwide and warrant a more focused research effort. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, III.

Intralesional corticosteroid administration in the treatment of keloids: a survey among Dutch dermatologists and plastic surgeons.

BACKGROUND: Intralesional corticosteroid administration (ICA) is a first-line therapy in keloid treatment. However, its clinical results are still highly variable and often suboptimal. Treatment results may strongly be influenced by various ways of ICA. OBJECTIVE: To explore the prevailing practice of ICA in keloid treatment among dermatologists and plastic surgeons in the Netherlands. METHODS: The survey was constructed based on a scoping review on ICA in keloid treatment. Members of the Dutch Society for Plastic surgery and the Dutch Society for Dermatology and Venereology were asked to participate. RESULTS: One hundred and thirty-six responses were obtained. One hundred and thirty (95.6%) participants used triamcinolone acetonide. The majority (54.7%) did not use local anesthesia for pain reduction. Reported corticosteroid dosing that one would inject in one specific keloid differed by a factor of 40. Treatment intervals varied from 1 week to more than 8 weeks. The keloid center was most often injected (46.9%), followed by subepidermal (18.0%). CONCLUSIONS: A wide variety in ICA for keloids is noted among dermatologists and plastic surgeons, even in a limited geographic region and when evidence points toward an optimal way of treatment. Future studies and better implementation of existing evidence may reduce variation in ICA and optimize its treatment results.

The JAK-STAT pathway in keloid pathogenesis: a systematic review with qualitative synthesis.

Keloid tissues contain inflammatory cells and upregulated pro-inflammatory cytokines. The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway mediate cellular responses to these cytokines. We performed a systematic review on the role of the JAK-STAT pathway in keloid pathogenesis and the evidence for JAK-STAT inhibitors in keloid treatment. The search combined the terms (1) keloid and (2) JAK or TYK or STAT and included MeSH terms and synonyms. Two reviewers screened the articles and assessed the full texts on eligibility. Data were collected on the tested drugs and molecules, the type of cells and tissues used in the experiments, and study findings on the association between the JAK-STAT pathway and keloid cells and tissues. A total of twenty preclinical studies were included. Eleven preclinical studies proved that STAT3 expression and phosphorylation are enhanced in keloid tissue and keloid fibroblasts. Thirteen different JAK and/or STAT inhibitors were investigated. Tested drugs inhibited keloid progression as demonstrated by different processes, including reduced collagen production, cell proliferation and migration, increased cell cycle arrest and apoptosis, enhanced antioxidant responses, decreased (paracrine) signalling, and decreased profibrotic gene expression. No clinical studies have been published to date. Preclinical studies indicate a role for the JAK-STAT pathway in keloid pathogenesis and a potential role for JAK-STAT inhibitors in keloid treatment. The effect of these drugs should be further investigated on relevant biomarkers in a human keloid skin model, preferably including immune cells besides keloid fibroblasts and keratinocytes and in clinical studies.

Intralesional Corticosteroid Administration in the Treatment of Keloids: A Scoping Review on Injection Methods.

BACKGROUND: Intralesional corticosteroid administration (ICA) is a first-line treatment for keloids. However, its clinical results are still highly variable and often suboptimal. Treatment results may strongly be influenced by various operator-dependent factors. The aim of this study was to map the details of ICA in keloids described in randomized controlled trials (RCTs), hence presenting the scientific practice of a first-line treatment for keloids in the best available evidence. SUMMARY: A systematic search was performed on PubMed, Ovid MEDLINE, Ovid EMBASE, and CENTRAL. Eligible studies were RCTs including patients with keloids treated with intralesional corticosteroids. Treatment and study design-related data were charted on a predefined form. Thirty-eight RCTs were included for data extraction. Triamcinolone acetonide was used in 37 (97.4%) studies. Dosing per cm2 could only be compared among ten (26%) studies and varied from 1 to 20 mg. The maximum dose per session varied from 20 to 80 mg. Local anesthetics were administered in seven (20%) RCTs. Treatment intervals varied from weekly to monthly, with 4 weeks most frequently (50%) used. Needle size was reported in eleven (29%) studies and varied from 26 to 30-gauge. Syringe size was specified in four (11%) studies, being 1 mL. The injection level was described in eleven (29%) studies. Blanching as endpoint was reported in ten (26%) studies. Outcome measures varied widely, from height, surface area, or volume, to Vancouver Scar Scale, Patient and Observer Scar Assessment Scale, pain and itch scores, patient satisfaction, and different efficacy rates. Only six studies had a follow-up of ≥6 months. Recurrence was identified in two studies with 18 weeks and 1 year of follow-up. Adverse events were reported in 23 (61%) studies.

No association found between late-onset inflammatory adverse events after soft tissue filler injections and the adaptive immune system.

BACKGROUND: To date, it is unknown why some individuals develop late-onset inflammatory adverse events after treatment with fillers. These events may result from various factors, including an immunological response of the adaptive immune system. OBJECTIVE: In a pilot study, we looked for evidence that is there a relation between late-onset inflammatory adverse events and the presence of immune cells surrounding the injected filler. METHODS AND MATERIALS: We included 47 patients, of whom 20 experienced late-onset inflammatory adverse events to different fillers (inflammatory group) and 27 who did not (reference group). A biopsy was taken from the area of the adverse event. Hematoxylin-eosin staining and immunohistochemistry analysis with CD3 (T-cells) and CD68 (macrophages) on paraffin tissue sections was used to assess the biopsies. RESULTS: Immune cells were found in biopsies obtained from 18 of 47 patients: Nine biopsies from the inflammation group and nine from the reference group. All these 18 cases showed CD68-positive immune cells. Virtually no CD3-positive immune cells were found. CONCLUSION: Our results indicate that there is no T-cell activity in biopsies from areas with late-onset adverse events after filler injections. The macrophages found in the biopsies are probably not responsible for the inflammatory response.

Bacterial Contamination Is Involved in the Etiology of Soft-Tissue Filler, Late-Onset, Inflammatory Adverse Events.

BACKGROUND: The treatment algorithm in late-onset inflammatory adverse events with soft-tissue fillers depends primarily on the assumed causative factor: immunologic or bacterial. METHODS: The authors included 29 patients, 13 of whom experienced late-onset inflammatory adverse events to fillers (inflammatory group) and 16 who did not (reference group). Biopsies were acquired from both groups with an 18-G needle. Before taking the biopsy, the authors acquired skin swabs for 25 of the 29 patients. The IS-pro method-a new and very sensitive method to detect microbiota-was used. This is a novel broad-range polymerase chain reaction technique based on length and sequence variations of the 16S to 23S ribosomal interspacer region. IS-pro can detect bacteria at low abundances and identify them up to species level. To exclude contamination from skin microbiota, the authors compared the microbiota found on skin swabs with that found in the corresponding biopsies. RESULTS: A high level of Gram-positive bacteria was found in biopsies of soft-tissue fillers, predominantly in patients from the inflammation group. This suggests that these bacteria were introduced during the primary filler injection treatment. The composition of the microbiota on the skin differed markedly from that in the filler, indicating that contamination during the sampling process did not influence results. CONCLUSIONS: Bacteria adherent to soft-tissue fillers or bacteremia probably play a causative role in adverse events. Contamination of samples in the biopsies with skin microbiota was excluded. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Patient-reported systemic symptoms in women with silicone breast implants: a descriptive cohort study.

OBJECTIVE: An unknown portion of women with silicone breast implants (SBI) report development of systemic symptoms, recently named as 'breast implant illness (BII)'. We aim to describe the symptoms and characteristics of women with SBI reporting these systemic symptoms and compare the clinical course of women who chose to keep their implants, to women who had their implants removed. DESIGN: Observational cohort study. SETTING: Specialised BII out-patient clinic at Amsterdam UMC, the Netherlands, from 2011 to 2020. PARTICIPANTS: All women presenting to the BII clinic with SBI and systemic symptoms. RESULTS: 467 women were included for baseline analyses and 398 women for follow-up. Most frequently reported systemic symptoms at baseline included fatigue (88%), arthralgia (71%), morning stiffness (59%), myalgia (48%), cognitive impairment (33%), peripheral neurological symptoms (30%) and lymphadenopathy (22%). Furthermore, 56% reported pre-existing allergies at baseline and positive antinuclear antibodies were observed in 23%. At follow-up with a median of 3.3 years (IQR 2-4), 152 women had their implants removed on clinical grounds. Symptoms improved significantly in 65 women (43%), improved moderately in 37 women (24%), did not change in 37 women (24%) and deteriorated in 13 women (9%). Women who underwent explantation showed more improvement of their systemic symptoms compared with women who did not (OR 2.9, 95% CI 1.3 to 6.2). Additionally, women who underwent explantation within 10 years after implantation improved significantly better than women who got the implants removed after 10 years (p=0.007). Lastly, local symptoms decreased from 75% to 34% after implant removal (p<0.0001). CONCLUSION: Most women with SBI who developed systemic symptoms experienced improvement after explantation, especially when removed within 10 years after implantation. Early recognition of the pattern of systemic symptoms in women with SBI is important and implant removal should be considered.

Inflammatory immune-mediated adverse reactions induced by COVID-19 vaccines in previously injected patients with soft tissue fillers: A case series of 20 patients.

BACKGROUND: Adverse events (AE) after COVID-19 vaccines, particularly, but not solely, with those messenger RNA (mRNA)-based vaccines, have rarely been reported in patients previously treated with dermal fillers (DF). OBJECTIVE: To evaluate the morphology, clinical characteristics, the timing of presentation, and outcomes of inflammatory AE appeared in patients injected with DF, after anti-COVID-19 vaccination. METHODS: Descriptive study of a case series of 20 consecutive patients collected after the occurrence of AE in previously filled areas post COVID-19 vaccination. RESULTS: From January 2021 to July 2021, we analyzed 20 AE reactions triggered by COVID-19 vaccines in the previously mentioned cohort. They were vaccinated with Pfizer/Biontech (11; 55%), Moderna (5; 25%), Astra-Zeneca (3; 15%), and Sputnik (1; 5%). The most common manifestations were oedema/swelling, angioedema, erythema, skin induration, and granuloma. Less common reactions included myalgia and lymphadenopathy. In 13/20 (65%) cases, the AE appeared after the first dose of vaccine. These inflammatory AE appeared more rapidly after the second dose than after the first one. In 13/20 (65%) cases, the symptomatology subsided with anti-inflammatory/antihistaminic drugs, while spontaneously in 3/20 (15%). The manifestations are ongoing.in the remaining four cases (20%). CONCLUSION: Although probably rare, both RNA-based and adenovirus-based anti-COVID-19 vaccines can cause inflammatory bouts in patients previously treated with DF. In these cases, caution should be paid on subsequent vaccine doses, considering a tailored risk/benefit for any case before next vaccination.

Parent grain reconstruction from partially or fully transformed microstructures in MTEX.

A versatile generic framework for parent grain reconstruction from fully or partially transformed child microstructures has been integrated into the open-source crystallographic toolbox MTEX. The framework extends traditional parent grain reconstruction, phase transformation and variant analysis to all parent-child crystal symmetry combinations. The inherent versatility of the universally applicable parent grain reconstruction methods and the ability to conduct in-depth variant analysis are showcased via example workflows that can be programmatically modified by users to suit their specific applications. This is highlighted by three applications, namely α'-to-γ reconstruction in a lath martensitic steel, α-to-ß reconstruction in a Ti alloy, and a two-step reconstruction from α' to ɛ to γ in a twinning and transformation-induced plasticity steel. Advanced orientation relationship discovery and analysis options, including variant analysis, are demonstrated via the add-on function library ORTools.

Scar formation from the perspective of complexity science: a new look at the biological system as a whole.

A burn wound is a complex systemic disease at multiple levels. Current knowledge of scar formation after burn injury has come from traditional biological and clinical studies. These are normally focused on just a small part of the entire process, which has limited our ability to sufficiently understand the underlying mechanisms and to predict systems behaviour. Scar formation after burn injury is a result of a complex biological system-wound healing. It is a part of a larger whole. In this self-organising system, many components form networks of interactions with each other. These networks of interactions are typically non-linear and change their states dynamically, responding to the environment and showing emergent long-term behaviour. How molecular and cellular data relate to clinical phenomena, especially regarding effective therapies of burn wounds to achieve minimal scarring, is difficult to unravel and comprehend. Complexity science can help bridge this gap by integrating small parts into a larger whole, such that relevant biological mechanisms and data are combined in a computational model to better understand the complexity of the entire biological system. A better understanding of the complex biological system of post-burn scar formation could bring research and treatment regimens to the next level. The aim of this review/position paper is to create more awareness of complexity in scar formation after burn injury by describing the basic principles of complexity science and its potential for burn care professionals.

Tissue Stromal Vascular Fraction Improves Early Scar Healing: A Prospective Randomized Multicenter Clinical Trial.

BACKGROUND: Wound healing and scar formation depends on a plethora of factors. Given the impact of abnormal scar formation, interventions aimed to improve scar formation would be most advantageous. The tissue stromal vascular fraction (tSVF) of adipose tissue is composed of a heterogenous mixture of cells embedded in extracellular matrix. It contains growth factors and cytokines involved in wound-healing processes, eg, parenchymal proliferation, inflammation, angiogenesis, and matrix remodeling. OBJECTIVES: The aim of this study was to investigate the hypothesis that tSVF reduces postsurgical scar formation. METHODS: This prospective, double-blind, placebo-controlled, randomized trial was conducted between 2016 and 2020. Forty mammoplasty patients were enrolled and followed for 1 year. At the end of the mammoplasty procedure, all patients received tSVF in the lateral 5 cm of the horizontal scar of 1 breast and a placebo injection in the contralateral breast to serve as an intrapatient control. Primary outcome was scar quality measure by the Patient and Observer Scar Assessment Scale (POSAS). Secondary outcomes were obtained from photographic evaluation and histologic analysis of scar tissue samples. RESULTS: Thirty-four of 40 patients completed follow-up. At 6 months postoperation, injection of tSVF had significantly improved postoperative scar appearance as assessed by the POSAS questionnaire. No difference was observed at 12 months postoperation. No improvement was seen based on the evaluation of photographs and histologic analysis of postoperative scars between both groups. CONCLUSIONS: Injection of tSVF resulted in improved wound healing and reduced scar formation at 6 months postoperation, without any noticeable advantageous effects seen at 12 months.

The Bigger Picture: Why Oral Mucosa Heals Better Than Skin.

Wound healing is an essential process to restore tissue integrity after trauma. Large skin wounds such as burns often heal with hypertrophic scarring and contractures, resulting in disfigurements and reduced joint mobility. Such adverse healing outcomes are less common in the oral mucosa, which generally heals faster compared to skin. Several studies have identified differences between oral and skin wound healing. Most of these studies however focus only on a single stage of wound healing or a single cell type. The aim of this review is to provide an extensive overview of wound healing in skin versus oral mucosa during all stages of wound healing and including all cell types and molecules involved in the process and also taking into account environmental specific factors such as exposure to saliva and the microbiome. Next to intrinsic properties of resident cells and differential expression of cytokines and growth factors, multiple external factors have been identified that contribute to oral wound healing. It can be concluded that faster wound closure, the presence of saliva, a more rapid immune response, and increased extracellular matrix remodeling all contribute to the superior wound healing and reduced scar formation in oral mucosa, compared to skin.

Laser treatment of specific scar characteristics in hypertrophic scars and keloid: A systematic review.

BACKGROUND: Hypertrophic scarring and keloid can cause significant emotional and physical discomfort. Cosmetic appearance, functional limitations, pain and pruritus form a degree of impairment. While the etiology is not fully known, there is a wide array of treatment options, which include excision, radiation, cryotherapy, silicone gel sheeting, and intralesional injections. A relatively new modality is laser therapy. While results are promising, the number of different laser systems is substantial. This review evaluates the available evidence regarding outcomes on specific objective characteristics (i.e., erythema, pigmentation, height, and pliability) of the different laser systems. METHODS: A systematic literature review was performed using MEDLINE, Cochrane Library, and EMBASE. Data on scar characteristics were extracted from scar scales Vancouver Scar Scale (VSS) and Patient and Observer Scar Assessment Scale (POSAS), and from objective measurement tools. RESULTS: Heterogeneity was seen in a lot of aspects: maturity of scar, origin of scar, follow-up, and number of treatments. The fractional ablative lasers CO2 10,600 nm and Er:YAG 2940 nm were found to produce the best results regarding erythema, height, and pliability, while the flash lamp-pumped pulsed dye laser (PDL) 585 nm scored slightly below that. CONCLUSIONS: Laser systems, and specifically the fractional ablative lasers CO2 and Er:YAG, improved various characteristics of excessive scarring. An overview of preferred laser modality per scar characteristic is presented. Accounting for the methodological quality and the level of evidence of the data, future research in the form of randomized trials with comparable standardized scar scales is needed to confirm these results.

Hypertrophic scars and keloids: Overview of the evidence and practical guide for differentiating between these abnormal scars.

Although hypertrophic scars and keloids both generate excessive scar tissue, keloids are characterized by their extensive growth beyond the borders of the original wound, which is not observed in hypertrophic scars. Whether or not hypertrophic scars and keloids are two sides of the same coin or in fact distinct entities remains a topic of much debate. However, proper comparison between the two ideally occurs within the same study, but this is the exception rather than the rule. For this reason, the goal of this review was to summarize and evaluate all publications in which both hypertrophic scars and keloids were studied and compared to one another within the same study. The presence of horizontal growth is the mainstay of the keloid diagnosis and remains the strongest argument in support of keloids and hypertrophic scars being distinct entities, and the histopathological distinction is less straightforward. Keloidal collagen remains the strongest keloid parameter, but dermal nodules and α-SMA immunoreactivity are not limited to hypertrophic scars alone. Ultimately, the current hypertrophic scars-keloid differences are mostly quantitative in nature rather than qualitative, and many similar abnormalities exist in both lesions. Nonetheless, the presence of similarities does not equate the absence of fundamental differences, some of which may not yet have been uncovered given how much we still have to learn about the processes involved in normal wound healing. It therefore seems pertinent to continue treating hypertrophic scars and keloids as separate entities, until such a time as new findings more decisively convinces us otherwise.

Increased risk of late-onset, immune-mediated, adverse reactions related to dermal fillers in patients bearing HLA-B*08 and DRB1*03 haplotypes.

Even though manufacturers claim that the dermal fillers are nontoxic and nonimmunogenic, adverse events may occur. Clinically and histologically, most of the late onset adverse events present as an inflammatory response. To assess whether HLA polymorphisms are associated with late-onset inflammatory adverse events related to dermal fillers. A total of 211 patients were included, of whom 129 experienced late-onset inflammatory adverse events to different fillers (Inflammation group) and 82 who did not (Reference group). Patients completed a standardized questionnaire and provided a blood sample or oral swap for HLA testing. The study population consisted of 188 (89%) women and 23 (11%) men. The two study groups were similar in the distributions of filler type, location of injecting, allergy, autoimmune disease, gender, age, ethnicity, and smoking status. Of the 211 patients in the sample, 25 had the combination of HLA subtype-B*08 and HLA subtype-DRB1*03. This was 16.3% of the inflammatory group and 4.9% of the reference group. This combination of HLA subtypes was associated with an almost 4-fold increase in the odds of developing immune mediated adverse events (odds ratio = 3.79, 95% CI 1.25-11.48). Genetic polymorphisms such as HLA combinations may identify patients at risk of developing late onset immune mediated adverse events to dermal fillers.

Prognostic tools for hypertrophic scar formation based on fundamental differences in systemic immunity.

Unpredictable hypertrophic scarring (HS) occurs after approximately 35% of all surgical procedures and causes significant physical and psychological complaints. Parallel to the need to understanding the mechanisms underlying HS formation, a prognostic tool is needed. The objective was to determine whether (systemic) immunological differences exist between patients who develop HS and those who develop normotrophic scars (NS) and to assess whether those differences can be used to identify patients prone to developing HS. A prospective cohort study with NS and HS groups in which (a) cytokine release by peripheral blood mononuclear cells (PBMC) and (b) the irritation threshold (IT) after an irritant (sodium lauryl sulphate) patch test was evaluated. Univariate regression analysis of PBMC cytokine secretion showed that low MCP-1, IL-8, IL-18 and IL-23 levels have a strong correlation with HS (P < .010-0.004; AUC = 0.790-0.883). Notably, combinations of two or three cytokines (TNF-a, MCP-1 and IL-23; AUC: 0.942, Nagelkerke R2 : 0.727) showed an improved AUC indicating a better correlation with HS than single cytokine analysis. These combination models produce good prognostic results over a broad probability range (sensitivity: 93.8%, specificity 86.7%, accuracy 90,25% between probability 0.3 and 0.7). Furthermore, the HS group had a lower IT than the NS group and an accuracy of 68%. In conclusion, very fundamental immunological differences exist between individuals who develop HS and those who do not, whereas the cytokine assay forms the basis of a predictive prognostic test for HS formation, the less invasive, easily performed irritant skin patch test is more accessible for daily practice.