Profibrotic Subsets of SPP1+ Macrophages and POSTN+ Fibroblasts Contribute to Fibrotic Scarring in Acne Keloidalis.

Acne keloidalis is a primary scarring alopecia characterized by longstanding inflammation in the scalp causing keloid-like scar formation and hair loss. Histologically, acne keloidalis is characterized by mixed leukocytic infiltrates in the acute stage followed by a granulomatous reaction and extensive fibrosis in the later stages. To further explore its pathogenesis, bulk RNA sequencing, single-cell RNA sequencing, and spatial transcriptomics were applied to occipital scalp biopsy specimens of lesional and adjacent no-lesional skin in patients with clinically active disease. Unbiased clustering revealed 19 distinct cell populations, including 2 notable populations: POSTN+ fibroblasts with enriched extracellular matrix signatures and SPP1+ myeloid cells with an M2 macrophage phenotype. Cell communication analyses indicated that fibroblasts and myeloid cells communicated by SPP1 signaling networks in lesional skin. A reverse transcriptomics in silico approach identified corticosteroids as possessing the capability to reverse the gene expression signatures of SPP1+ myeloid cells and POSTN+ fibroblasts. Intralesional corticosteroid injection greatly reduced SPP1 and POSTN gene expression as well as acne keloidalis disease activity. Spatial transcriptomics and immunofluorescence staining verified microanatomic specificity of SPP1+ myeloid cells and POSTN+ fibroblasts with disease activity. In summary, the communication between POSTN+ fibroblasts and SPP1+ myeloid cells by SPP1 axis may contribute to the pathogenesis of acne keloidalis.

Acne Keloidalis Nuchae and the Metabolic Syndrome: A Population-Based Study.

BACKGROUND: The association between acne keloidalis nuchae (AKN) and the metabolic syndrome (MS) has been reported anecdotally. However, it is yet to be investigated in the setting of controlled studies, leaving this topic inconclusive in the current literature. OBJECTIVE: The aim was to estimate the association between AKN and the MS and its components, utilizing one of the largest cohorts of patients with AKN. METHODS: A retrospective, population-based, cross-sectional study was performed between 2005 and 2018. We utilized the database of Clalit Health Services, the largest public healthcare provider organization in Israel. The current study encompassed data collected from general community clinics, primary care, and referral centers, as well as from ambulatory and hospital care. RESULTS: A total of 2677 patients with AKN and 13,190 controls were included. The prevalence of the MS was greater in patients with AKN than in control subjects (16.1% vs. 6.6%, respectively; odds ratio [OR] 2.72; 95% confidence interval [CI] 2.40-3.08; P < 0.001). Obesity demonstrated the strongest association with AKN (OR 3.00; 95% CI 2.75-3.28), followed by type 2 diabetes mellitus (OR 2.47; 95% CI 2.20-2.77), hypertension (OR 1.82; 95% CI 1.63-2.05), and dyslipidemia (OR 1.60; 95% CI 1.46-1.75). Estimates were not altered significantly after controlling for putative confounding factors. CONCLUSIONS: A strong association was observed between AKN and the MS on the one hand, and with every one of its four components on the other. Physicians treating patients with AKN should be aware of this possible comorbidity. Patients with AKN should be carefully assessed for comorbid metabolic disorders.

Noninvasive evaluation of collagen and hemoglobin contents and scattering property of in vivo keloid scars and normal skin using diffuse reflectance spectroscopy: pilot study.

Collagen is a rich component in skin that provides skin structure integrity; however, its contribution to the absorption and scattering properties of various types of skin has not been extensively studied. We considered the contribution of the collagen to the absorption spectrum of in vivo normal skin and keloids of 12 subjects derived from our diffuse reflectance spectroscopy (DRS) system in the wavelength range from 550 to 860 nm. It was found that the collagen concentration, the hemoglobin oxygen saturation, and the reduced scattering coefficient of keloids were remarkably different from that of normal skin. Our results suggest that our DRS system could assist clinicians in understanding the functional and structural condition of keloid scars. In the future, we will evaluate the accuracy of our system in the keloid diagnosis and investigate the applicability of our system for other skin-collagen-related studies.

Long-term organ culture of keloid disease tissue.

Keloid disease (KD) is a common fibroproliferative disorder of unknown aetiopathogenesis, with highly unsatisfactory treatment. Therefore, it is crucial to have a robust and clinically relevant model for studying KD pathobiology as well as preclinical testing of potential KD therapeutics. However, the unique occurrence of KD in human skin and the corresponding lack of animal models pose a major challenge in KD research. Therefore, we developed a simplified assay for the serum-free, long-term organ culture of KD tissue that facilitates quantitative analyses of major KD read-out parameters. Four millimetre KD punches embedded in a collagen matrix and organ-cultured at the epidermis air-liquid interphase (ALI) in supplemented William's E medium showed optimal tissue, cell and RNA preservation for up to 6 weeks (as measured by H & E and Pyronin Y histochemistry as well as by MTT assay, lactate dehydrogenase release and quantitative Ki67/TUNEL immunohistomorphometry). The keloid phenotype persisted well during this period, as shown by collagen-I and -III synthesis (Herovici's histochemistry staining and ELISA), and analysis of the expression of significant KD markers (CD3, CD20, CD31, CD34, CD56, tryptase, Langerin, vimentin, neutrophil elastase, CTGF and Collagen). To functionally evaluate whether this assay can test the response to candidate therapeutics, dexamethasone, a glucocorticosteroid often used in KD therapy, was administered. Indeed, dexamethasone significantly reduced the keloid volume and cellularity plus induced epidermal shrinkage. Therefore, this novel assay provides a quantitative, clinically relevant model system for studying KD pathobiology and response to treatment.