Acquired cutis laxa (ACL) is a rare, nonhereditary cutaneous disorder characterized by saggy inelastic skin. It has been associated with various inflammatory, autoimmune, and neoplastic diseases, in addition to certain infections and medication. This article reviews ACL the demographical, clinical, and histological features of ACL, focusing on all associated disorders. Additionally, this review article provides an in-depth discussion of all the mechanisms implicated in the pathogenesis of ACL and all therapeutic options available; we also present an algorithm for the workup of patients with ACL. A systematic literature review was performed on PubMed/Medline and EMBASE databases, searching for all available articles on ACL with no limits on participant age, race, sex, nationality, or publication date. Ninety-eight articles were included. The total number of included patients was 110, with a mean age of 36.4 years at presentation (range 0.25-78) and a M:F sex ratio of 1.24. ACL was most commonly associated with inflammatory disorders (43%) followed by neoplastic disorders (27%). In 73% of the neoplastic-associated cases, ACL occurred on average 2.4 years before malignancy onset. ACL occurs months to years after an underlying inflammatory disorder. In 10% of the cases, ACL was associated with a particular drug, and in 2%, it was associated with specific infections. Data were derived from case reports, case series, letters to editors, observational studies, and abstracts. Limitations include the accuracy of published data, potential patient selection, and reporting bias. Dermatologists should be alert to these associations to provide adequate screening and management of patients with ACL.

BACKGROUND: The appearance of striae gravidarum (SG) during pregnancy is a common problem. The most common SG are abdominal striae, which can cause the greatest sequelae after pregnancy, and in the long term. There are several solutions to prevent and treat these striae, but not all are completely effective, and not without side effects.
OBJECTIVE: The aim of this study was to evaluate the effectiveness of a treatment that applies an electromagnetic field under vacuum (V-EMF therapy) on the abdominal SG.
METHODS: A retrospective analysis was conducted on the medical records of 26 women affected by abdominal SG and treated with V-EMF therapy. The results were evaluated using two different 5-point Likert Scales: one administered to the treated subjects to evaluate their satisfaction, and one to the doctors who performed the treatment, to evaluate the improvement of the striae. The presence of side effects, and the effects of sun exposure after treatment were also considered.
RESULTS: Only two treated subjects rated their level of satisfaction with a Score III on the Liker Scale. Everyone else expressed higher levels of satisfaction. Only one doctor rated the improvement of the striae with a Liker scale score of III. All the others reported greater improvements. No discomfort or side effects were noted either during the individual treatment sessions, or at the end of the treatment. The striae showed a newfound ability to tan.
CONCLUSIONS: V-EMF therapy proves to be a valid, safe, and effective treatment modality for SG.

Muscles and fasciae are mutually connected and are influenced by force transmission. However, the anatomical connectivity and histological features of these structures remain unclear. The aim of this study was to assess the evidence for connection between muscles and deep/muscular fasciae. We assessed this relationship in different topographical regions of human cadavers and in mice. The results showed that myofascial junctions (MFJ) were made up of collagen I immune-positive structures occupying an average area of 5.11 ± 0.81 μm2, distributed in discrete regions at the interface between muscle and fascia with an average density of 9.7 ± 2.51 MFJ/mm and an average inclination angle of 35.25 ± 1.52°. These specialized structures also showed collagen III and HA immunopositivity and the presence of elastic fibers. The human myofascial junction can be visualized, opening emerging insights into the connection between deep/muscular fascia and muscle.

Cutis laxa is a rare connective tissue disorder, characterized by a reduced number and abnormal properties of elastic fibers throughout the dermis, creating a clinical appearance of premature aging. It can be subdivided into inherited and acquired, the latter rarer than the former, and skin involvement may be localized or generalized. The etiology of acquired cutis laxa (ACL) remains unknown and there is no definitive treatment. We present the case of a 30-year-old man diagnosed with type I ACL with progressive systemic involvement at the renal, pulmonary, and digestive levels. Histological analysis of the skin revealed reduction and fragmentation of elastic fibers. Immunosuppressive treatment was started with prednisone, cyclophosphamide, and rituximab, with which a complete response to proteinuria was achieved and the progression of lung damage was limited. Autoimmune, infectious, and neoplastic diseases were ruled out.

Developing an effective treatment for pulmonary emphysema will require a better understanding of the molecular changes responsible for distention and rupture of alveolar walls. A potentially useful approach to studying this process involves the concept of emergence in which interactions at different levels of scale induce a phase transition comprising a spontaneous reorganization of chemical and physical systems. Recent studies in our laboratory provide evidence of this phenomenon in pulmonary emphysema by relating the emergence of airspace enlargement to the release of elastin-specific desmosine and isodesmosine (DID) crosslinks from damaged elastic fibers. When the mean alveolar diameter exceeded 400 μm, the level of peptide-free DID in human lungs was greatly increased, reflecting rapid acceleration of elastin breakdown, alveolar wall rupture, and a phase transition to an active disease state that is less responsive to treatment. Based on this finding, it is hypothesized that free DID in urine and other body fluids may serve as a biomarker for early detection of airspace enlargement, thereby facilitating timely therapeutic intervention and reducing the risk of respiratory failure.

Advanced maternal age during pregnancy is associated with increased risk of vaginal tearing during delivery and maladaptive postpartum healing. Although the underlying mechanisms of age-related vaginal injuries are not fully elucidated, changes in vaginal microstructure may contribute. Smooth muscle cells promote the contractile nature of the vagina and contribute to pelvic floor stability. While menopause is associated with decreased vaginal smooth muscle content, whether contractile changes occur before the onset of menopause remains unknown. Therefore, the first objective of this study was to quantify the active mechanical behavior of the murine vagina with age. Further, aging is associated with decreased vaginal elastin content. As such, the second objective was to determine if elastic fiber disruption alters vaginal contractility. Vaginal samples from mice aged 2-14 months were used in maximum contractility experiments and biaxial extension-inflation protocols. To evaluate the role of elastic fibers with age, half of the vaginal samples were randomly allocated to enzymatic elastic fiber disruption. Contractile potential decreased and vaginal material stiffness increased with age. These age-related changes in smooth muscle function may be due, in part, to changes in microstructural composition or contractile gene expression. Furthermore, elastic fiber disruption had a diminished effect on smooth muscle contractility in older mice. This suggests a decreased functional role of elastic fibers with age. Quantifying the age-dependent mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties provides a first step towards better understanding how age-related changes in vaginal structure may contribute to tissue integrity and healing. STATEMENT OF SIGNIFICANCE: Advanced maternal age at the time of pregnancy is linked to increased risks of vaginal tearing during delivery, postpartum hemorrhaging, and the development of pelvic floor disorders. While the underlying causes of increased vaginal injuries with age and associated pathologies remain unclear, changes in vaginal microstructure, such as elastic fibers and smooth muscle cells, may contribute. Menopause is associated with fragmented elastic fibers and decreased smooth muscle content; however, how reproductive aging affects changes in the vaginal composition and the mechanical properties remains unknown. Quantifying the mechanical contribution of smooth muscle cells and elastic fibers to vaginal properties with age will advance understanding of the potential structural causes of age-related changes to tissue integrity and healing.

BACKGROUND: The process by which functional elastic fibers are produced, namely elastogenesis, is complex and difficult to assess in vitro. Identifying efficient elasticity-boosting ingredients thus represents a challenge.
OBJECTIVE: The elasticity-boosting properties of a novel extract of Murraya koenigii leafy stems were assessed in vitro in 3D culture models before being evaluated in human female volunteers.
METHODS: Synthesis of elastic fiber related proteins was evaluated in a skin-equivalent model. Using multiphoton microscopy, the structural organization of elastin deposits was studied within a scaffold-free dermal microtissue. Biomechanical properties of the 3D microtissue were also measured by atomic force microscopy. In vivo, fringe-projection and image analysis were used to evaluate nasogenian fold severity in a panel of Caucasian female volunteers. The impact of gravity on visible signs of facial aging was assessed by clinical scoring carried out alternatively in the supine and sitting positions.
RESULTS: We showed the Murraya koenigii extract increased protein expressions of elastin and fibrillin-1 in a 3D skin equivalent model. Using scaffold-free dermal microtissue, we confirmed that Murraya koenigii extract allowed a proper and ordered network of elastin deposits and consequently improved tissue elasticity. Clinical data showed that a twice-daily application for 98 days of the extract formulated at 1% allowed to visibly reduce nasogenian fold severity, jowl severity and to mitigate the impact of gravity on the facial signs of aging.
CONCLUSIONS: The newly discovered extract of Murraya koenigii leafy stems represents an innovative antiaging ingredient suited for elasticity-boosting and antisagging claims.

OBJECTIVE: To compare the collagen, elastic fibers, and smooth muscle content of the clitoris and the glans penis in young adults.
METHODS: The clitoris and the glans penis of six women and six men (mean age 25±3) who died as a result of accidents were excised. The samples were placed under a formaldehyde solution and histologically processed. Masson\'s trichrome and Weigert\'s resorcin-fuchsin stain was used to highlight the elastic fibers, smooth muscle, and collagen. Stereological analysis was conducted in 5 random fields of 5 slides for each sample. For statistical analysis, the unpaired t-test was used to compare values between groups, and a value of P<0.05 was considered as significant for all analyses.
RESULTS: Stereology revealed a mean smooth muscle content of 35.84±6.46% and 31.64±4.74% for the clitoris and glans penis, respectively, while it also revealed collagen content of 26.11±7.41% and 28.44±3.55% and elastic fibers content of 24.12±4.34% and 30.97±6.13% for the clitoris and glans penis, respectively. The statistical analysis showed no significant differences between them.
CONCLUSIONS: Regardless of anatomical differences, the volumetric density of collagen, elastic fibers, and smooth muscle were similar for the clitoris and glans penis in young adults, a feature possibly explained by their embryology.

Preterm infants with oxygen supplementation are at high risk for bronchopulmonary dysplasia (BPD), a neonatal chronic lung disease. Inflammation with macrophage activation is central to the pathogenesis of BPD. CXCL10, a chemotactic and pro-inflammatory chemokine, is elevated in the lungs of infants evolving BPD and in hyperoxia-based BPD in mice. Here, we tested if CXCL10 deficiency preserves lung growth after neonatal hyperoxia by preventing macrophage activation. To this end, we exposed Cxcl10 knockout (Cxcl10-/-) and wild-type mice to an experimental model of hyperoxia (85% O2)-induced neonatal lung injury and subsequent regeneration. In addition, cultured primary human macrophages and murine macrophages (J744A.1) were treated with CXCL10 and/or CXCR3 antagonist. Our transcriptomic analysis identified CXCL10 as a central hub in the inflammatory network of neonatal mouse lungs after hyperoxia. Quantitative histomorphometric analysis revealed that Cxcl10-/- mice are in part protected from reduced alveolar. These findings were related to the preserved spatial distribution of elastic fibers, reduced collagen deposition, and protection from macrophage recruitment/infiltration to the lungs in Cxcl10-/- mice during acute injury and regeneration. Complimentary, studies with cultured human and murine macrophages showed that hyperoxia induces Cxcl10 expression that in turn triggers M1-like activation and migration of macrophages through CXCR3. Finally, we demonstrated a temporal increase of macrophage-related CXCL10 in the lungs of infants with BPD. In conclusion, our data demonstrate macrophage-derived CXCL10 in experimental and clinical BPD that drives macrophage chemotaxis through CXCR3, causing pro-fibrotic lung remodeling and arrest of alveolarization. Thus, targeting the CXCL10-CXCR3 axis could offer a new therapeutic avenue for BPD.

BACKGROUND: Granuloma annulare (GA) has diverse clinical manifestations, multiple subtypes, and unknown etiology and pathogenesis. Existing studies regarding GA in children are scarce.
OBJECTIVE: To examine the correlation between clinical manifestation and histopathology of pediatric GA.
METHODS: A total of 39 patients under 18 years of age with both a clinical and pathological diagnosis of GA at Kunming Children\'s Hospital from 2017 to 2022 were retrieved. Their medical records were consulted, and clinical data of the children were recorded and summarized, including gender, age, disease site, etc. Existing wax blocks of skin lesion specimens of children and pathological films were retrieved for further study and relevant histology, including hematoxylin-eosin, Alcian blue, elastic fiber (Victoria blue-Lichon red method), and antacid staining. Finally, the children\'s clinical manifestations, histopathological results, and special staining characteristics were analyzed.
RESULTS: The clinical manifestations of granuloma annulare in children were diverse: 11 cases presented with a single lesion, 25 with multiple lesions, and 3 with generalized lesions. The pathological typing comprised histiocytic infiltration, palisading granuloma, epithelioid nodular, and mixed types in 4, 11, 9, and 15 cases, respectively. Thirty-nine cases were negative for antacid staining. The positive rate of Alcian blue staining was 92.3%, and that of elastic fiber staining was 100%. The degree of elastic fiber dissolution and granuloma annulare histopathological typing were positively correlated (r = 0.432, P < 0.05). No correlation was found between clinical presentation and histopathological typing of the granuloma annulare in children. In the pathological diagnosis of granuloma annulare, the positive elastic fiber staining rate was higher than that of Alcian blue staining. A correlation was found between elastic fiber dissolution degree and histopathological staging. However, the differences in pathological staging may have been related to the pathological manifestation of granuloma annulare at different periods.
CONCLUSIONS: Elastic fiber degradation may be a critical step in the pathogenesis of pediatric granuloma annulare. This is also one of the first studies focused on granuloma annulare in children.