Hereditary hemorrhagic telangiectasia, or Osler-Weber-Rendu syndrome, is a rare autosomal dominant vascular disorder characterized by dysregulated angiogenesis due to abnormalities in the transforming growth factor-β (TGF-β)/bone morphogenetic protein (BMP) signaling pathway that result in mucocutaneous telangiectasias and visceral arteriovenous malformations, leading to recurrent bleeding and multisystem involvement. This image-based case highlights characteristic mucocutaneous telangiectasias and illustrates the challenges of long-term disease management, including recurrent hospitalizations and limited durability of vascular interventions. The case emphasizes the importance of coordinated outpatient care and consideration of targeted therapies to reduce morbidity and bleeding recurrence.

Addison's disease, or primary adrenal insufficiency, is a rare endocrine disorder characterized by deficient glucocorticoid and mineralocorticoid production, frequently associated with cutaneous hyperpigmentation due to chronic elevation of adrenocorticotropic hormone. Facial hyperpigmentation may persist despite adequate hormonal replacement, representing a therapeutic challenge with limited evidence to guide dermatologic management. We report the case of a 41-year-old female patient with an eight-year history of progressive hyperpigmentation affecting the face, hands, and oral mucosa. Physical examination revealed severe facial involvement with brown-violaceous macules and associated telangiectasias. The patient had a prior diagnosis of autoimmune ovarian failure in 2017 and was diagnosed with Addison's disease in 2020, receiving stable glucocorticoid replacement therapy. Histopathological evaluation demonstrated basal layer hyperpigmentation without interface dermatitis, consistent with endocrine-related pigmentation and overlapping melasma features. A multimodal therapeutic approach was implemented, including picosecond Nd:YAG laser therapy (approximately seven sessions at six- to eight-week intervals), oral tranexamic acid (250 mg twice daily), and a topical depigmenting regimen containing tranexamic acid, niacinamide, retinoids, and antioxidants. The patient demonstrated a significant reduction in modified Melasma Area and Severity Index score from 19.8 to 7.8 (60.6% reduction), along with a marked improvement in quality of life, as evidenced by a posttreatment Melasma Quality of Life Scale score of 20/70. This case highlights that persistent hyperpigmentation in Addison's disease may not fully resolve with endocrine treatment alone and may require adjunctive dermatologic interventions. A personalized, multimodal strategy targeting multiple pathogenic pathways, including melanogenesis, plasmin-mediated signaling, vascular factors, and dermal pigment deposition, can achieve significant improvement, even in patients with darker phototypes and long-standing disease. These findings underscore the importance of a multidisciplinary approach and suggest a potential role for combination therapies, including laser-based modalities, in managing complex pigmentary disorders associated with systemic conditions. Further studies are needed to establish standardized treatment protocols and evaluate long-term outcomes.

Rhinophyma is a deforming disease that affects the nose mainly of Caucasian men. Progressive nasal skin thickening, telangiectasias, and hypertrophy of sebaceous appendages are frequently found in these patients. Many therapeutic modalities have been reported with good results. Among these, tangential excision is established as the surgical modality of choice. In advanced cases, it is not possible to distinguish nasal deformities resulting from rhinophyma from those resulting from malposition of the anatomic components that make up the nasal framework. We describe the use of a mixed technique in which the tangential excision and the open approach complement each other satisfactorily, restoring both shape and structure of the nose. This approach may represent a safe alternative for the simultaneous treatment of rhinophyma and a structured rhinoplasty, and further studies are needed for its full validation in clinical practice.

Ataxia Telangiectasia (A-T) is a neurodegenerative disorder characterized by early onset, cerebellar ataxia and progressive motor decline. The causative gene, ATM (A-T Mutated), encodes a Ser/Thr kinase, that belongs to the phosphoinositide 3-kinase-related protein kinase family and is crucial for the response to DNA double-strand breaks. While ATM is classically known for its role in the DNA damage response, increasing evidence points to its critical function in maintaining cellular homeostasis, particularly in the central nervous system (CNS). Yet the mechanisms linking ATM-kinase deficiency to cerebellar circuit dysfunction remain poorly defined. Using a CNS Nestin-Cre-restricted mouse model carrying a kinase-dead Atm allele combined with a null allele (Atm[KDF/CNS-KO]), we integrated proteomics, structural and ultrastructural analyses, electrophysiology, and behavioral testing to understand how the loss of Atm kinase activity influence the cerebellar microenvironment from the earliest stages of the disease. Proteomic profiling revealed alterations across four major pathways in Atm[KDF/CNS-KO] mice, such as disorganization of the extracellular matrix (ECM), astrocytosis, downregulation of myelin and oligodendrocyte lineage proteins and changes in neuronal excitability. Histological and electron microscopy analyses confirmed increased ECM deposition, astrocytosis and reduction of myelin content without axonal or oligodendrocyte loss, consistent with impaired myelination at early stages. These microenvironmental changes were associated to Purkinje cell dark cell degeneration and increased intrinsic excitability, demonstrating early circuit dysfunction in the absence of overt neuronal loss. Consistently, the compromised cerebellar output is confirmed by the progressive motor impairment developed by Atm[KDF/CNS-KO] mice. Our findings indicate that Atm kinase deficiency disrupts cerebellar homeostasis through interconnected and bidirectional mechanisms involving ECM remodeling, astrocytosis, impaired oligodendrocyte functioning and altered intrinsic excitability, reflecting a network level destabilization of the cerebellar microenvironment.

Kaposiform hemangioendothelioma is a rare vascular tumor of endothelial origin that occurs during the first decade of life. It is locally aggressive, with a tendency for local invasion and spread to regional lymph nodes. It presents as tender, expanding plaques, nodules, papules, or telangiectasias and is most commonly located in the retroperitoneum and skin; however, involvement of the head and neck region is uncommon. Herein, we report an unusual case of kaposiform hemangioendothelioma in a 59-year-old woman who presented with a several-month history of right-sided nasal obstruction and epistaxis. Contrast-enhanced computed tomography revealed an enhancing mass originating from the right inferior turbinate. The patient underwent endoscopic excision of the endonasal mass with any postoperative complications.

Hereditary haemorrhagic telangiectasia (HHT) is an uncommon autosomal dominant vascular disorder, most frequently associated with pathogenic variants in ENG or ACVRL1, resulting in multisystem arteriovenous malformations (AVMs). We report a middle-aged woman with primary antiphospholipid syndrome on chronic enoxaparin therapy who presented with exertional dyspnoea. CT demonstrated bilateral pulmonary AVMs (PAVMs), and clinical evaluation revealed mucocutaneous telangiectasias. Genetic testing identified an ENG mutation, confirming HHT type 1 according to the three Curaçao criteria. Selective microcoil embolisation of PAVMs with feeding arteries >3 mm led to marked improvement in functional capacity. HHT1 is predominantly associated with pulmonary and cerebral AVMs, whereas HHT2 and juvenile polyposis-hereditary haemorrhagic telangiectasia syndrome involve hepatic and gastrointestinal manifestations. Diagnostic assessment relies on echocardiographic contrast studies and CT angiography. Embolisation represents the standard of care for significant PAVMs with periodic radiological surveillance recommended. This case underscores the importance of early recognition and multidisciplinary management to mitigate HHT-associated complications.

The eukaryotic ATAXIA-TELANGIECTASIA AND RAD3-RELATED (ATR) kinase is essential for ensuring genomic integrity under conditions that cause replication defects. It triggers a transient cell cycle arrest and DNA repair by activating the DNA damage response (DDR) pathway. While ATR kinases appear to be functionally conserved, species-specific phenotypes can be observed across the plant kingdom. To investigate the ancestral roles of the plant ATR, we identified its homolog in the model liverwort Marchantia polymorpha, which we named MpATR. Similar to other plant species, MpATR preserves meristematic cells during replication stress, whereas it mediates the response to double-strand breaks redundantly with ATAXIA-TELANGIECTASIA MUTATED (MpATM). However, unlike its counterpart in vascular plants, MpATR activity in liverwort is also essential for repressing the proliferation of differentiated cells. Furthermore, M. polymorpha does not rely on MpATR-controlled stem cell death to eliminate malignant cells. Moreover, even under control growth conditions, Mpatr mutants exhibit increasingly severe growth defects across successive vegetative clonal generations, which are aggravated in the Mpatm/atr double mutant, underscoring the critical role of MpATR in sustaining normal growth over successive generations. Overall, our study sheds light on the differential dependency on ATR in liverwort versus vascular plants, emphasizing its evolutionary adaptation across plant species.

Esophageal squamous cell carcinoma (ESCC) is aggressive with poor prognosis, frequently driven by chemotherapy resistance. Kinesin family member 18B (KIF18B) is implicated in tumor progression, but its role in ESCC chemoresistance remains unclear. To investigate KIF18B's clinical relevance and mechanistic contribution to oxaliplatin resistance in ESCC, KIF18B expression was analyzed in TCGA data, ESCC cell lines/tissues (qPCR, Western blot, IHC), and correlated with survival (Kaplan-Meier). Results showed that, KIF18B was significantly elevated in ESCC and correlated with shorter overall/progression-free survival. Knockdown reversed oxaliplatin resistance, reducing IC50 from 8.5 µM to 3 µM, restoring apoptosis, and inducing G2/M arrest. Silencing suppressed the ATR/CHK1 pathway (reduced p-ATR, p-CHK1, WEE1, CDC25A) and increased γH2AX foci. Co-IP confirmed KIF18B-ATR interaction, suggesting stabilization of DNA damage signaling. In vivo, KIF18B knockdown synergized with oxaliplatin, achieving > 80% tumor suppression and reduced Ki-67/p-ATR/p-CHK1 levels. In conclusion, KIF18B is a prognostic biomarker and therapeutic target in ESCC. Its inhibition overcomes oxaliplatin resistance by disrupting KIF18B-ATR interaction and ATR/CHK1-mediated DNA repair. Combining KIF18B targeting with chemotherapy or ATR inhibitors represents a promising strategy for refractory ESCC.