Type I interferonopathies are a heterogeneous group of monogenic autoinflammatory disorders characterized by dysregulated type I interferon (IFN-I) signaling due to pathogenic variants that affect nucleic acid sensing, processing, or downstream signaling pathways. Mutations in genes including TREX1, RNASEH2A/B/C, SAMHD1, ADAR1, STING1 (TMEM173), PSMB8, COPA, and DNASE1L3 lead to persistent activation of innate immune pathways, particularly the cGAS-STING, MDA5, and Toll-like receptor pathways, with subsequent JAK-STAT signaling and sustained overexpression of interferon-stimulated genes. Chronic IFN-I activation promotes endothelial dysfunction, vascular inflammation, and tissue injury, providing a mechanistic link between interferonopathies and vasculitic disorders. Clinically, these conditions present with diverse manifestations, including chilblains, livedo reticularis, necrotizing cutaneous vasculopathy, panniculitis, interstitial lung disease, cerebral vasculopathy, and glomerulonephritis, often resembling autoimmune diseases such as primary central nervous system vasculitis, systemic lupus erythematosus (SLE), poliarteritis nodosa (PAN), immune complex vasculitis, and ANCA-associated vasculitis (AAV). A persistently elevated interferon gene signature represents a valuable diagnostic biomarker that distinguishes these disorders from most classical autoimmune vasculitides and facilitates early recognition. Timely genetic testing is essential to establish an accurate diagnosis, guide patient management, and avoid treatment delays. The present review summarizes the molecular mechanisms linking IFN-I dysregulation to endothelial injury and vasculitis, discusses the clinical spectrum and diagnostic challenges of monogenic interferonopathies, and highlights emerging targeted therapies, particularly Janus kinase inhibitors, that support precision medicine approaches for interferon-driven inflammatory diseases.

VEXAS syndrome (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) is a novel autoinflammatory disorder caused by somatic mutations in the UBA1 gene. It predominantly affects older males, though cases in females with X-chromosome mosaicism have been reported in the literature. Dermatologic manifestations, found in up to 90% of cases, are significant diagnostic clues and may include erythematous plaques, Sweet syndrome-like lesions, and livedo reticularis. VEXAS syndrome poses significant diagnostic challenges due to its overlap with hematologic, autoimmune, and inflammatory disease. Hallmark findings include macrocytic anemia, myeloid vacuolization, and the presence of UBA1 mutations. Current treatment options include corticosteroids, biologics, and hematopoietic stem cell transplantation, but data on long-term efficacy is limited. Advances in understanding the epidemiology, pathophysiology, and treatment of VEXAS syndrome will be essential in improving diagnostic accuracy and patient outcomes.

Biopsy for reticulate eruptions such as livedo reticularis and livedo racemosa representing an underlying vasculitis or vessel occlusion presents a challenge for most clinicians. Sampling errors frequently occur due to the difficulty in selecting the most appropriate and histologically representative site for biopsy. Here we describe a new technique where ultrasound is used to guide the biopsy with pinpoint accuracy to the affected vessel.

Background and Clinical Significance: Hyaluronic acid fillers are currently the most widely used materials in aesthetic medicine and represent one of the most frequently performed minimally invasive procedures worldwide. Vascular occlusion is the most severe complication associated with this type if filler injections due to the risk of tissue necrosis and permanent sequelae. Early recognition and precise identification of the affected vascular territory are essential to prevent irreversible damage. Case Presentation: his report describes a case of infraorbital artery occlusion with retrograde extension to the anterior superior alveolar artery and associated gingival ischemia, highlighting the role of high-frequency ultrasound in diagnosis and management. A 60-year-old woman developed vascular occlusion following supraperiosteal HA injection in the medial cheek. Clinical findings included livedo reticularis in the infraorbital and nasal regions, along with ipsilateral gingival anesthesia and mucosal ischemia. High-frequency ultrasound was used to assess the extent and mechanism of vascular involvement. A targeted treatment approach was implemented using low-dose hyaluronidase (100 IU/mL), with 200 IU administered in the infraorbital region and an additional 100 IU delivered under ultrasound guidance to the affected alveolar branch. Ultrasound examination revealed extrinsic compression of the infraorbital artery and secondary occlusion of the anterior superior alveolar artery consistent with retrograde embolization. Following image-guided administration of hyaluronidase, complete reperfusion was achieved, with resolution of both cutaneous and gingival ischemia and no functional or aesthetic sequelae. Conclusions: High-frequency ultrasound provides critical diagnostic information in vascular complications after HA filler injection, allowing for accurate identification of the mechanism and extent of vascular involvement. Ultrasound-guided low-dose hyaluronidase may represent an effective and safe strategy to restore perfusion while minimizing unnecessary enzyme exposure and associated adverse effects.

Livedoid vasculopathy is a rare, chronic thrombo-occlusive disease characterized by recurrent livedoid skin changes, atrophic white plaques, and ulceration. It most commonly affects the dermal vessels of the distal lower extremities, ankles, and feet, bilaterally. While it is commonly associated with hypercoagulable states, systemic autoimmune diseases, and malignancies, we report a case of a previously healthy 31-year-old female with a history of moderate COVID-19 infection during pregnancy, two years before the onset of livedoid skin changes. The patient presented to a hematologist with a two-month history of erythematous to violaceous macules and patches on the dorsum of the feet, ankles, and lower extremities, along with mild ankle swelling. Multiple punch biopsies of the affected skin demonstrated thrombi, fibrinoid vascular changes, fibrosis, and hyalinization of the vessel walls - findings consistent with vasculopathy. Initial treatment included subcutaneous low-molecule weight heparin (dalteparin). This case highlights the importance of early recognition, the performance of a skin biopsy with subsequent histopathologic diagnosis, and appropriate management of this rare, but potentially debilitating condition.

Patients with thrombotic antiphospholipid syndrome (APS) or subjects with persistent presence of antiphospholipid antibodies (aPLA), defined "carriers", may develop thrombocytopenia. However, the prevalence and clinical characteristics associated with thrombocytopenia remain poorly understood. We aimed to describe the prevalence and the clinical characteristics associated with thrombocytopenia in APS patients and aPLA carriers included in the Survey on AnTicoAgulated Patients-RegisTry on antiphospholipid antibodies (START-APS), a multicentre prospective registry. Thrombocytopenia was defined as a platelet count < 150 × 10[9]/L, while moderate-to-severe form was defined as < 100 × 10[9]/L. Logistic regression analysis was performed, and results were expressed as Odds Ratio (OR) and 95% confidence interval (95%CI). A total of 464 patients were included (148 aPLA carriers, 316 APS), mean age was 57.3 ± 15.6 years, and 66.5% were women. 63 (13.6%) patients presented with thrombocytopenia; 15.2% in APS patients and 10.1% in aPLA carriers (p = 0.138). Overall, triple positive pattern (OR 1.90, p = 0.002), livedo reticularis (OR 3.57, p = 0.029), heart failure (OR 4.52, p = 0.039), and female sex (OR 0.59, p = 0.011) were associated with thrombocytopenia. Triple positivity (OR 5.44, p < 0.001) and history of myocardial infarction (OR 6.52, p = 0.009) were associated with moderate-to-severe thrombocytopenia. Thrombocytopenia may occur early also in aPLA carriers, raising to 15% in APS patients, especially in those presenting with triple positivity and cardiovascular involvement. This association was confirmed also with moderate-to-severe thrombocytopenia.

ObjectiveTo describe the prevalence, clinical manifestations, histopathological features, and antibody profile associated to skin involvement in patients with catastrophic antiphospholipid syndrome (CAPS).MethodsWe performed a cross-sectional study of the patients included in the "CAPS Registry," a registry developed by the European Forum on Antiphospholipid Antibodies (aPL)1,2 This database contains data from patients with CAPS collected from April 1992 to December 2024. Demographic clinical manifestations, laboratory features (including aPL antibodies), pathological findings in involved skin, and outcome were retrieved.ResultsCutaneous involvement was described in 377 episodes (47%) from 361 patients. A female sex prevalence of 49.4% was observed. The average age was 39.4 (SD ± 17.9) years. The more frequent skin manifestations observed were livedo reticularis (17.6%), skin necrosis (13%), ischemic ulcers (10.4%), skin ischemic (9.7%), skin purpura (7.1%), gangrene (5%), splinter haemorrhages (2.6%), and Raynaud's phenomenon (1.5%). The most frequently affected organs in CAPS episodes with skin involvement were kidneys (72%), lungs (61%), central nervous system (54.5%), and heart (54.4%). Thrombocytopenia and hemolysis features were more common in patients with skin involvement (p < 0.05 for all). Thrombotic microangiopathy was the predominant pathological finding, present in 82 (68.3%) episodes. No difference regarding mortality were found in episodes with or without skin involvement (29.3% vs 32.1%, p = 0.42).ConclusionThe presence of skin involvement in patients with CAPS is frequent. The most frequent manifestations were livedo reticularis and skin necrosis. Skin involvement does not seem to be associated to mortality.

Background: Vascular adverse events (VAEs) related to facial filler injections are rare but potentially severe complications. Doppler ultrasound has emerged as an adjunct imaging tool for evaluating vascular compromise; however, Doppler findings in facial VAEs remain insufficiently characterized. Objectives: To characterize Doppler ultrasound findings associated with filler-related facial VAEs and to assess whether Doppler patterns differ according to prior hyaluronidase administration. Methods: This international multicenter retrospective observational study included 100 patients with clinically diagnosed facial VAEs following filler injections between May 2022 and April 2025. Doppler ultrasound findings were analyzed, including absent flow in perforators and major arteries, compensatory flow, abnormal waveforms, increased peak systolic velocity (PSV), and absence of Doppler abnormalities. Patients were categorized according to hyaluronidase administration prior to ultrasound evaluation. Descriptive statistics and comparative analyses were performed. Results: One hundred patients (median age, 38 years; IQR: 30-50; 88 women) were evaluated. The most frequent Doppler ultrasound findings were absent flow in perforators (42%) and major arteries (35%), followed by compensatory flow (26%), string sign (18%), flow diversion (16%), and increased peak systolic velocity (16%). No Doppler abnormalities were observed in 12% of cases, while tardus-parvus (9%) and staccato waveform (8%) were less frequent. Doppler ultrasound findings did not differ significantly between patients who received hyaluronidase before imaging and those who did not (all p > 0.05). The dose of hyaluronidase varied substantially. Livedo reticularis, blanching, and pain were the most common clinical findings. Central facial arterial territories, particularly the perioral, nasolabial fold, nasal, and glabellar regions, were most commonly involved. Conclusions: Filler-related facial VAEs show recognizable Doppler ultrasound patterns, and the identification of these patterns may improve localization of vascular occlusion and support ultrasound-guided hyaluronidase administration, potentially enabling more targeted delivery with lower doses.

West Nile virus neuroinvasive disease (WNND) most commonly presents as meningitis, encephalitis, or acute flaccid paralysis, with variable neuroimaging findings. While MRI abnormalities classically involve deep gray matter and brainstem structures, hemorrhagic manifestations are rarely reported. We report a 77-year-old woman who presented with rapidly progressive altered mental status following a brief febrile prodrome. Cerebrospinal fluid studies demonstrated a lymphocytic pleocytosis consistent with aseptic meningitis. Brain MRI revealed an acute lacunar infarct and diffuse cerebral microhemorrhages initially concerning for cerebral amyloid angiopathy. During hospitalization, she developed livedo reticularis-like peripheral skin changes prompting evaluation for autoimmune or vasculitic etiologies. Extensive infectious and autoimmune testing was ultimately notable for positive serum and CSF West Nile virus serologies, confirming neuroinvasive WNV infection. Despite transient neurologic improvement, her clinical course deteriorated, and she died following transition to comfort-focused care. This case highlights diffuse cerebral microhemorrhages as a potential finding in WNND, although their attribution remains uncertain. These findings may reflect underlying neurovascular inflammatory injury related to WNV or may represent coincident pathology and can mimic other small-vessel or autoimmune pathologies, complicating early diagnostic evaluation. Recognition of this expanded radiographic and clinical spectrum may aid timely diagnosis of WNND in patients with atypical presentations.