Association of plasminogen activator inhibitor-1 and vitamin D receptor expression with the risk of keloid disease in a Chinese population.

Keloid disease (KD) is a benign fibroproliferative scarring condition of unknown etiopathogenesis. Plasminogen activator inhibitor-1 (PAI-1) and vitamin D receptor (VDR) have been shown to play important roles in the progression of tissue fibrosis; therefore, both these genes are potential susceptibility genes for KD. We aimed to determine whether the gene expression levels of PAI-1 and VDR are altered in Chinese KD patients. We measured the expression of PAI and VDR in human peripheral blood lymphocytes in 236 patients with keloid and 219 age- and sex-matched healthy controls by quantitative real-time polymerase chain reaction. We found that PAI-1 expression in peripheral blood lymphocytes was significantly higher in patients with KD than in control individuals (p < 0.0001), while VDR expression was significantly lower in KD patients than in control individuals (p < 0.0001). High levels of PAI-1 and low levels of VDR expression were significantly associated with an increased risk for KD. PAI-1 and VDR might play important roles in keloid development. Gene expression levels of PAI-1 and VDR may, therefore, be used as potential markers for the prediction of keloid development after scarring.

Ethnic skin: Kids are not just little people.

There are numerous skin conditions that occur commonly in children with ethnic skin, including vitiligo, progressive macular hypomelanosis, pityriasis alba, acne keloidalis nuchae, pseudofolliculitis barbae, and keloids. Though these conditions occur in both children and adults, children may have different patterns of clinical presentation and response to therapy. In caring for such patients, important treatment considerations include side effects of systemic medications and tolerability of invasive procedures. Quality of life is an important measure and should not be compromised by either the skin disease or its treatment.

Algorithm of chest wall keloid treatment.

Keloids are common in the Asian population. Multiple or huge keloids can appear on the chest wall because of its tendency to develop acne, sebaceous cyst, etc. It is difficult to find an ideal treatment for keloids in this area due to the limit of local soft tissues and higher recurrence rate. This study aims at establishing an individualized protocol that could be easily applied according to the size and number of chest wall keloids.A total of 445 patients received various methods (4 protocols) of treatment in our department from September 2006 to September 2012 according to the size and number of their chest wall keloids. All of the patients received adjuvant radiotherapy in our hospital. Patient and Observer Scar Assessment Scale (POSAS) was used to assess the treatment effect by both doctors and patients. With mean follow-up time of 13 months (range: 6-18 months), 362 patients participated in the assessment of POSAS with doctors.Both the doctors and the patients themselves used POSAS to evaluate the treatment effect. The recurrence rate was 0.83%. There was an obvious significant difference (P < 0.001) between the before-surgery score and the after-surgery score from both doctors and patients, indicating that both doctors and patients were satisfied with the treatment effect.Our preliminary clinical result indicates that good clinical results could be achieved by choosing the proper method in this algorithm for Chinese patients with chest wall keloids. This algorithm could play a guiding role for surgeons when dealing with chest wall keloid treatment.

Histomorphometric analysis of collagen architecture of auricular keloids in an Asian population.

BACKGROUND: Keloids are a pathologic condition of the reparative process, which present as excessive scar formation that involves various cells and cytokines. Many studies focusing on the histologic feature of keloids, however, have shown discordant results without consideration of architectural aspect of collagen structure. OBJECTIVE: The purpose of this study was to demonstrate a schematic illustration of collagen architecture of keloids, specifically auricular keloids, and to analyze each part on the histomorphologic and morphometric basis. MATERIALS AND METHODS: Thirty-nine surgically excised auricular keloids were retrieved from the file of Kangbuk Samsung Hospital. After exhaustive histomorphologic analysis, 3 distinctive structural parts, keloidal collagen, organizing collagen, and proliferating core collagen, were identified and mapped in every case. Cellularity of fibroblasts, blood vessel density, degree of inflammatory cell infiltration, and mast cells counts using Masson trichrome stain, Van Gieson stain, toluidine blue stain, and immunohistochemical stains for CD31 and smooth muscle actin were analyzed in each part of each case. Morphometric analysis on these parameters using ImageJ software was performed using 3 representative images of each part. RESULTS: Three parts were histomorphologically distinct by shape and array of collagen bundles, fibroblasts cellularity, blood vessel density, degree of inflammatory cells, and mast cell infiltration. Morphometric analysis revealed statistically significant difference between each part in fibroblasts cellularity, blood vessel density, degree of inflammatory cell infiltration, and mast cells count. All parameters were exceedingly high in whorling hypercellular fibrous nodules in proliferating core collagen showing simultaneous changes in other parts. CONCLUSION: Morphologically and morphometrically, 3 distinctive parts were identified in auricular keloids. Mast cell infiltrations, blood vessel density, and fibroblast cellularity are simultaneously increased or decreased according to these parts. Proliferating core collagen might serve as a proliferating center of keloids and might be a key portion for tumor growth and recurrence.

Clinical and epidemiological analysis of keloids in Chinese patients.

Keloids are common abnormally raised fibroproliferative lesions that can occur following even minor cutaneous trauma. There are limited data on Chinese patients with keloids, and the purpose of our study was to investigate the clinical and epidemiological features of keloids in Chinese patients. Assessment was performed by unified, designed questionnaires. A total of 715 patients were enrolled and statistical analysis and heritability were performed using EPI INFO 6.0, SPSS13.0 and Falconer's method. Keloids occurred typically between the ages of 10 and 30 years, and the mean age of initial onset was 21.14 ± 13.45 years in females and 22.55 ± 11.36 years in males. The difference in the mean age of onset was not significant between males and females (p > 0.05). A greater severity of keloids was observed in the positive history family group than in the negative history family group, and this difference was statistically significant (χ (2) = 10.889, p < 0.05). The formation of keloids in multiple anatomical sites was found to be significant in the positive family history group. This difference was statistically significant (χ (2) = 15.47, p < 0.001). The prevalence of keloids in first-, second- and third-degree relatives of the proband with keloids was 7.62, 0.38 and 0.035 %, respectively. These results were higher than those in controls and the difference of the prevalence rates of first- and second-degree relatives between probands and controls was significant (χ (2) = 224.63 and 12.078, respectively, p < 0.001). The heritability of keloids in first-, second- and third-degree relatives was 72.45, 40.55 and 17.07 %, respectively. Our findings revealed that the most severe forms of keloids were observed in the probands with positive family history, and the heritability in first-degree relatives of probands was 72.45 %. It is certain, therefore, that genetic factors play a role in the hereditary composition of keloids.

Differential susceptible loci expression in keloid and hypertrophic scars in the Chinese Han population.

BACKGROUND: Hypertrophic scars (HSs) and keloids (KDs) are commonly seen as 2 different diseases. We aimed to find potential genes associated with KD and HS formation. METHODS: We selected 4 single-nucleotide polymorphisms (SNPs) (based on the whole genome resequencing we have done) for replication in 71 KDs and 50 HSs using the Sequenom Massarray system. RESULTS: We found evidence of significant association at rs181924090, P = 0.0075; rs183178644, P = 0.0151; and rs151091483, P = 0.0073. However, at rs141156594, there was no significant association between KD and HS (P = 0.7893). CONCLUSIONS: rs181924090 (11p15.5, SIRT3), rs151091483 (17p13.1, MYH8), and rs183178644 (6p25.3, HUS1B) are new potential SNPs associated with KD formation, especially closely related to tumor behaviors as KD is, whereas rs141156594 (18q22.2, RTTN) is a new SNP involved in the extracellular matrix formation in wound healing.

Clinical implications of single- versus multiple-site keloid disorder: a retrospective study in an Asian population.

BACKGROUND: There is strong evidence of genetic susceptibility in individuals with keloid disorder. The purpose of this cross-sectional study was to determine the clinical relevance of our proposed variables on the multiplicity of keloids by further investigating the presence of other keloids and a family history. METHODS: This was a retrospective review, using institutional review board-approved questionnaires, of patients with keloids who were seen at Kangbuk Samsung Hospital between December 2002 and February 2010. Eight hundred sixty-eight patients were included in our study. Comparisons between the 2 groups were made using Mann-Whitney tests for continuous variables and χ2 tests for categorical variables. RESULTS: In our patient group, younger age of onset and the presence of family history were significantly associated with the occurrence of keloids at multiple sites. The locations of extra-auricular keloids, in order of frequency, included the shoulder; anterior chest, including the breasts; deltoid; trunk and pubic area; upper extremities; lower extremities; and other sites. As compared to secondary keloids, primary keloids were significantly associated with both a lower degree of recurrence and the presence of other keloids. The presence or absence of family history was significantly associated with the presence or absence of other keloids and primary or secondary keloids. CONCLUSIONS: Keloid disorder is one of the most frustrating problems in wound healing and advances in our understanding of the differences of occurrence at a single site versus multiple sites might help in understanding pathogenesis and improving treatment.

Admixture mapping identifies a locus at 15q21.2-22.3 associated with keloid formation in African Americans.

Keloids are benign dermal tumors that occur ~20 times more often in African versus Caucasian descent individuals. While most keloids occur sporadically, a genetic predisposition is supported by both familial aggregation of some keloids and the large differences in risk among populations. Yet, no well-established genetic risk factors for keloids have been identified. In this study, we conducted admixture mapping and whole-exome association using 478 African Americans (AAs) samples (122 cases, 356 controls) with exome genotyping data to identify regions where local ancestry associated with keloid risk. Logistic regression was used to evaluate associations under admixture peaks. A significant mapping peak was observed on chr15q21.2-22.3. This peak included NEDD4, a gene previously implicated in a keloid genome-wide association study (GWAS) of Japanese individuals later validated in a Chinese cohort. While we observed modest evidence for association with NEDD4, a more significant association was observed at (myosin 1E) MYO1E. A genome scan not including the 15q21-22 region also identified associations at MYO7A (rs35641839, odds ratio [OR] = 4.71, 95% confidence interval [CI] 2.38-9.32, p = 8.34 × 10(-6)) at 11q13.5. The identification of SNPs in two myosin genes strongly associated with keloid formation suggests that an altered cytoskeleton contributes to the enhanced migratory and invasive properties of keloid fibroblasts. Our findings support the admixture mapping approach for the study of keloid risk, and indicate potentially common genetic elements on chr15q21.2-22.3 in causation of keloids in AAs, Japanese, and Chinese populations.

Keloid incidence in Asian people and its comorbidity with other fibrosis-related diseases: a nationwide population-based study.

Keloids is a fibroproliferative disease. The incidence of keloids among Asians has not been thoroughly studied. The objective of this study is to determine the incidence of keloids in Taiwan, which mainly consists of ethnic Chinese. Furthermore, we want to determine the comorbidity rate of other fibrosis-related diseases among keloid patients. This study was based on the National Health Insurance Research Database, which contains the data of 1 million randomly selected patients. Multivariate logistic regression analyses were employed to estimate the relative odds of keloids as a function of fibrosis-related diseases. The annual keloid incidence rate in Taiwan was 0.15 % for the general population. With a 1.33 ratio, women outnumbered men. Women with uterine leiomyoma have a 2.25-fold greater risk of keloids, compared with women without leiomyoma. We concluded that keloid incidence in Taiwan is approximately 0.15 %. Women with leiomyoma have a greater risk of keloids, this implicates that both diseases share a common etiopathological pathway.

New insights on keloids, hypertrophic scars, and striae.

This article presents an overview of the literature regarding treatments for keloid disease, hypertrophic scars, and striae distensae in dark pigmented skin. Striae, keloid, and hypertrophic scarring present a challenging problem for both the clinician and patient. No single therapy is advocated for hypertrophic scars, keloid scars, or striae distensae. New therapies have shown promise in the treatment of hypertrophic and keloid scars, and in patients with dark pigmented skin. This article provides guidance on the assessment and determination of patients' suitability for certain treatment options, as well as advice on the follow-up of patients affected with problematic scarring and striae.

Strategic management of keloid disease in ethnic skin: a structured approach supported by the emerging literature.

Keloid disease (KD) is a common, benign, dermal fibroproliferative growth of unknown aetiology. Lesions tend to grow over time; they often recur following therapy and do not regress spontaneously. KD causes considerable discomfort due to pain, pruritus and inflammation, and a significant psychosocial impact with reduced quality of life. It is unique to humans and occurrence is higher in individuals with dark, pigmented, ethnic skin. There is a strong familial heritability, with a high ethnic predisposition in individuals of African, Asian and Hispanic descent. High recurrence rates and unknown resolution rates present a major problem for both the patient and clinician. Many treatment modalities exist; however, there is no single advocated therapy. Therefore, the aim of this review was to explore the most current literature regarding the range of treatment options for KD and to offer a structured approach in the management of KD, based on evidence and experience, to aid clinicians in their current practice. A focused history involving careful evaluation of the patient's symptoms, signs, quality of life and psychosocial well-being should direct targeted therapy, complemented with regular follow-up and re-evaluation. Many treatment modalities, such as intralesional steroid injection, silicone gel application, cryotherapy, lasers, 5-fluorouracil and, relatively recently, photodynamic therapy, are currently being used in clinical practice for the management of KD. Combination therapies have also been shown to be beneficial. However, there is a lack of robust, randomized, level-one, evidence-controlled trials evaluating these treatment options. Management of KD in ethnic pigmented skin remains a clinical challenge. Thus, a strategic approach with structured assessment, targeted therapy and focus on prevention of recurrence is highly recommended. Quality evidence is essential in order to tailor treatment effectively for the ethnic patient presenting with KD.

Comparison of cosmetic outcomes of absorbable versus nonabsorbable sutures in pediatric facial lacerations.

OBJECTIVE: We sought to compare cosmetic outcomes, complication rates, and patient/caregiver satisfaction of absorbable versus nonabsorbable sutures in children. METHODS: Healthy patients, 1 to 18 years old, with facial lacerations 1 to 5 cm, were randomized to repair with fast-absorbing catgut (FAC) or nylon (NYL) sutures. Patients returned in 4 to 7 days and in 3 to 4 months, at which time photographs and caregiver surveys were completed. Unlike part I, all FAC sutures were permitted to absorb rather than be removed. Using a 100-mm visual analog scale (VAS), a noninferiority (NI) design was applied, with a difference of less than 15 mm considered clinically equivalent. Caregivers and 3 blinded physicians independently rated the scars via photographs. RESULTS: Ninety-eight patients were enrolled, 76 caregiver surveys were completed, and 61 (29 FAC, 32 NYL) had photographs scored by physicians. The mean physician VAS scores for FAC and NYL were 57.6 and 67.6, respectively (difference, -10.0; 95% confidence interval, -19.1 to -0.4); thus, NI could not be established. The mean caregiver VAS scores for the FAC and NYL groups were 93.8 and 86.6, respectively (difference, 7.2; 95% confidence interval, -4.9 to 13.9); thus, NI of FAC was established. There were no significant differences in rates of infection, wound dehiscence, or keloid formation. In terms of future preference, caregivers favored FAC (33/33) over NYL (26/36) (P < 0.01). CONCLUSIONS: Caregiver VAS scores showed NI of FAC, which were also preferred by the caregivers. However, NI for FAC could not be demonstrated by blinded physicians with respect to cosmetic outcomes.

Keloids and ultrasound detected fibroids in young African American women.

OBJECTIVE: Keloids and fibroids share a number of biologic and demographic similarities however there are no published reports of the association between them. The objective of this study was to investigate the association between self-reported keloids and ultrasound detected fibroids in a population of young African American women. STUDY DESIGN: The Study of Environment, Life-style & Fibroids (SELF), is a volunteer cohort of over 1600 African American women aged 23-34 years recruited in Detroit, Michigan. Enrollment occurred between December 2010 and December 2012. Data are available for the first 1196 participants. Participants self-reported a history of raised (hypertrophic) scars or scars extending beyond the limits of the original injury (keloid) and had an enrollment pelvic ultrasound examination to detect prevalent fibroids. Log linear regression was used to model the association between abnormal scars and prevalent fibroids controlling for possible covariates. Among women with fibroids, associations between particular fibroid characteristics (tumor location, size or number) and scarring were assessed using chi-square and Mann Whitney U-tests. RESULTS: Both abnormal scarring (keloids, 9.0%; hypertrophic scars, 28.3%) and fibroids (23.3%) were common in this cohort. There was no indication [adjusted Risk Ratio (95% Confidence Interval): 0.7 (0.5-1.1)] of an association between self-reported keloids and prevalent fibroids. Nor was there any association with hypertrophic scars. Specific characteristics of the prevalent fibroids were not associated with abnormal scarring. CONCLUSION: Despite similarly dysregulated extracellular matrices in keloids and fibroids, these conditions did not tend to co-occur in this young African American population.

Assessment of the influence of HLA class I and class II loci on the prevalence of keloid disease in Jamaican Afro-Caribbeans.

Keloid disease (KD) is a common abnormal cutaneous fibrotic disorder of unknown aetiopathogenesis. KD is reported to have a strong genetic component as it is often familial and has a high incidence in certain ethnicities, in particular those of Afro-Caribbean origin. Genetic risk factors combined with aberrant lesional inflammatory responses point to the human leukocyte antigen (HLA) system as a viable target for investigating disease aetiology. Sequence specific primer polymerase chain reaction with allele sequencing was used to determine HLA-DQA1 and DQB1 allele frequencies (AF) for 165 KD patients and 119 healthy controls of black Jamaican Afro-Caribbean origin. HLA class I alleles A*01, A*03, A*25, B*07 and Cw*08:02, previously identified as KD associated in a different ethnicity, were also analysed. Allele sequencing confirmed typing accuracy but no statistically significant differences in AF were identified between KD patients and controls. Furthermore, KD subgroups including patient gender, family history and multiple- or single-site scarring did not show significant allele-disease associations.

Association of HLA haplotype with keloids in Chinese Hans.

Keloids are common abnormal raised fibroproliferative lesions that can occur following even minor cutaneous trauma. Human leukocyte antigen (HLA) polymorphisms have shown strong association with susceptibility to keloids with different ethnic backgrounds. In this study, the polymerase chain reaction sequence-specific primer method was used to analyze the distribution of HLA haplotype in 192 patients with keloids and 252 healthy control individuals. Controls were matched by gender, age, and race. We compared haplotype between the two groups, and analyzed their association with keloids. The haplotype analysis revealed that three new two-locus haplotypes including B*07-DQB1*0501, B*07-DRB1*15, DQB1*0503-DRB1*15 (P<0.05) were associated with keloids, while two extended haplotypes B*07-Cw*0802-DQB1*0501 (P=0.0063) and Cw*0802-DQB1*0501-DRB1*15 (P=0.0121) were found to be related to keloids. This is the first detailed report to elucidate HLA haplotypes associated with keloids. Our results provide some information for future research on predisposing genes in major histocompatibility complex (MHC) regions in Chinese patients with keloids. In addition, the association of certain HLA haplotypes with susceptibility to keloids would provide clues in choosing proper preventive strategies.

Prospective study of intraabdominal adhesions among women of different races with or without keloids.

OBJECTIVE: We sought to evaluate postsurgical adhesions in women of different races with or without keloids. STUDY DESIGN: This was a prospective study evaluating postsurgical adhesions after a cesarean delivery in 429 women with or without keloids. The outcome measures were the prevalence and extent of adhesions in women of different races with or without keloids. RESULTS: There was no difference in the prevalence of adhesions and adhesion score in various sites among women of different races. Compared with whites (0.5%), keloids were significantly more common in African Americans (7.1%; P = .007; odds ratio, 16.5) and in Asians (5.2%; P = .02; odds ratio, 11.9). Women with keloids were found to have more dense adhesions between the uterus and the bladder (P = .028; 95% confidence interval, 0-12) and between the uterus and the anterior abdominal wall (P < .0001; 95% confidence interval, 8-12). CONCLUSION: The prevalence and degree of postsurgical adhesions in women of different races are comparable. Women with keloids on the cesarean scar have increased adhesions between the uterus and the bladder and between the uterus and the abdominal wall.

Update on the management of keloids.

Keloids are scars, unique to humans, that grow beyond the boundaries of a cutaneous injury, inflammation, burn, or surgical incision. Although benign, keloids are often aesthetically malignant. The etiology of keloids is uncertain. However, we do know that they occur more often in African-American and Asian than Caucasian patients. There is no one therapeutic modality that either prevents the formation of keloids or treats active or inactive lesions. Consequently, there are many therapeutic options. In this review, an approach to medical and surgical management of keloids is provided, as well as a review of experimental therapeutic modalities.

Description of familial keloids in five pedigrees: evidence for autosomal dominant inheritance and phenotypic heterogeneity.

BACKGROUND: Familial keloids have been reported, having either autosomal dominant or autosomal recessive inheritance. We wished to determine the inheritance pattern and phenotype of keloids among multigenerational families, as a prelude to a positional mapping strategy to identify candidate genes. METHODS: We studied three African American families, one Afro-Caribbean family and one Asian-American family. Phenotyping including assessing all patients for the presence, distribution, and appearance of keloids, together with the timing of keloid onset and provocative factors. The clinical trial was registered at clinicaltrials.gov (NCT 00005802). RESULTS: Age of keloid onset varied considerably within families, but commonly occurred by the second decade. The fraction of affected individuals was 38%, 45%, 62%, 67% and 73% among the five families respectively. Keloid severity and morphology differed within and between families. A novel finding is that certain families manifest keloids in distinct locations, with one family showing an excess of extremity keloids and two families showing an excess of axilla-groin keloids. CONCLUSION: Familial keloids appear to most commonly manifest autosomal dominant or semidominant inheritance, and there may be familial patterns of keloid distribution.