Keloid risk in patients with atopic dermatitis: a nationwide retrospective cohort study in Taiwan

Lu, Ying‐Yi; Lu, Chun‐Ching; Yu, Weifang; Zhang, Li; Zhang, Cong-Liang; Wu, Chieh‐Hsin

doi:10.1136/bmjopen-2018-022865

Cited by 29 publications

(26 citation statements)

References 64 publications

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“…Clinical associations between keloids and other Th2-skewed diseases (e.g. AD (23) and asthma (24)) have also been reported. However, to our knowledge, a transcriptomic profiling of keloid skin lesions, that attempts to elucidate their immune alterations is lacking.…”

Section: Introductionmentioning

confidence: 94%

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

Duca

Espino

et al. 2020

Front. Immunol.

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Keloids are disfiguring, fibroproliferative growths and their pathogenesis remains unclear, inhibiting therapeutic development. Available treatment options have limited efficacy and harbor safety concerns. Thus, there is a great need to clarify keloid pathomechanisms that may lead to novel treatments. In this study, we aimed to elucidate the profile of lesional and non-lesional keloid skin compared to normal skin. We performed gene (RNAseq, qRT-PCR) and protein (immunohistochemistry) expression analyses on biopsy specimens obtained from lesional and non-lesional skin of African American (AA) keloid patients compared to healthy skin from AA controls. Fold-change≥2 and false-discovery rate (FDR)<0.05 was used to define significance. We found that lesional versus normal skin showed significant up-regulation of markers of T-cell activation/migration (ICOS, CCR7), Th2- (IL-4R, CCL11, TNFSF4/OX40L), Th1- (CXCL9/CXCL10/CXCL11), Th17/Th22- (CCL20, S100As) pathways, and JAK/STAT-signaling (JAK3) (false-discovery rate [FDR]<0.05). Non-lesional skin also exhibited similar trends. We observed increased cellular infiltrates in keloid tissues, including T-cells, dendritic cells, mast cells, as well as greater IL-4rα+, CCR9+, and periostin+ immunostaining. In sum, comprehensive molecular profiling demonstrated that both lesional and non-lesional skin show significant immune alternations, and particularly Th2 and JAK3 expression. This advocates for the investigation of novel treatments targeting the Th2 axis and/or JAK/STAT-signaling in keloid patients.

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Section: Introductionmentioning

confidence: 94%

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

Duca

Espino

et al. 2020

Front. Immunol.

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“…All diagnoses in the analysis were coded according to the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM). First, 17,401 patients with keloids (ICD-9-CM code 701.4) were identified in the LHID 58 , 59 . A comparison group of 69,604 patients without keloids were then matched at a ratio of 1:4 for age, age group, gender, and region of residence by propensity scores.…”

Section: Methodsmentioning

confidence: 99%

Risk of cancer development in patients with keloids

Lü

et al. 2021

Sci Rep

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Keloid is a skin disease characterized by exaggerated scar formation, excessive fibroblast proliferation, and excessive collagen deposition. Cancers commonly arise from a fibrotic microenvironment; e.g., hepatoma arises from liver cirrhosis, and oral cancers arise from submucosal fibrosis. As keloids are a prototypic fibroproliferative disease, this study investigated whether patients with keloids have an increased cancer risk. In a matched, population-based study, first 17,401 patients treated for keloids during 1998–2010 with 69,604 controls without keloids at a ratio of 1:4 were evaluated. The association between keloids and risk of cancer was estimated by logistic regression or Cox proportional hazard regression models after adjustment of covariates. In total, 893 first-time cases of cancer were identified in the 17,401 patients with keloids. The overall cancer risk was 1.49-fold higher in the keloids group compared to controls. Regarding specific cancers, the keloids group, had a significantly higher risk of skin cancer compared to controls (Relative risk = 1.73). The relative risk for skin cancer was even higher for males with keloids (Relative risk = 2.16). Further stratified analyses also revealed a significantly higher risk of developing pancreatic cancer in female patients with keloids compared to controls (Relative risk = 2.19) after adjustment for known pancreatic cancer risk factors. This study indicates that patients with keloids have a higher than normal risk for several cancer types, especially skin cancers (both genders) and pancreatic cancer (females). Therefore, patients with keloids should undergo regular skin examinations, and females with keloids should regularly undergo abdominal ultrasonography.

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“…All disease diagnoses were based on the International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) codes. The analysis included 8597 patients with keloids (ICD9-CM code: 701.4) diagnosed by a dermatologist or plastic surgeon for the first time [ 18 , 19 ]. The occurrence of keloids was defined as > 2 diagnoses of keloids in ambulatory visits or > 1 diagnoses of keloids in inpatient care.…”

Section: Methodsmentioning

confidence: 99%

The association between keloid and osteoporosis: real-world evidence

Qin

Zhang

et al. 2021

BMC Musculoskelet Disord

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Background Keloids are characterized by disturbance of fibroblast proliferation and apoptosis, deposition of collagen, and upregulation of dermal inflammation cells. This benign dermal fibro-proliferative scarring condition is a recognized skin inflammation disorder. Chronic inflammation is a well-known contributor to bone loss and its sequelae, osteoporosis. They both shared a similar pathogenesis through chronic inflammation. We assessed whether keloids increase osteoporosis risk through using National Health Insurance Research Database. Methods The 42,985 enrolled patients included 8597 patients with keloids but no history of osteoporosis; 34,388 controls without keloids were identified from the general population and matched at a one-to-four ratio by age, gender. Kaplan-Meier method was applied to determine cumulative incidence of osteoporosis. Cox proportional hazard regression analysis was performed after adjustment of covariates to estimate the effect of keloids on osteoporosis risk. Results Of the 8597 patients with keloids, 178 (2.07%) patients were diagnosed with osteoporosis while in the 34,388 controls, 587 (1.71%) were diagnosed with osteoporosis. That is, the keloids patients had 2.64-fold higher risk of osteoporosis compared to controls after adjustment for age, gender, Charlson Comorbidity Index and related comorbidities. The association between keloids and osteoporosis was strongest in patients younger than 50 years (hazard ratio = 7.06%) and in patients without comorbidities (hazard ratio = 4.98%). In the keloids patients, a high incidence of osteoporosis was also associated with advanced age, high Charlson Comorbidity Index score, hyperlipidemia, chronic liver disease, stroke, and depression. Conclusions Osteoporosis risk was higher in patients with keloids compared to controls, especially in young subjects and subjects without comorbidities.

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Keloid risk in patients with atopic dermatitis: a nationwide retrospective cohort study in Taiwan

Cited by 29 publications

References 64 publications

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

RNA Sequencing Keloid Transcriptome Associates Keloids With Th2, Th1, Th17/Th22, and JAK3-Skewing

Risk of cancer development in patients with keloids

The association between keloid and osteoporosis: real-world evidence

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