Ataxia-telangiectasia (A-T) is a rare inherited autosomal recessive disease. It is associated with an alteration in the ATM gene, located on chromosome 11q22-23, which codes for a protein involved in a complex way in cell cycle regulation and cell protection. It is characterized by cerebellar ataxia, cutaneous and ocular telangiectasia, and an immune deficiency responsible for recurrent infections. Diagnosis is generally delayed due to the late onset of neurological symptoms and telangiectasia. People suffering from this condition are particularly sensitive to ionizing radiation, which considerably increases their risk of developing neoplasia. We report an observation of a primary immunodeficiency-type A-T revealed by recurrent fever and multiple splenic abscesses.

Telangiectases and arteriovenous malformations (AVMs) are the characteristic lesions of Hereditary Hemorrhagic Telangiectasia (HHT). Somatic second-hit loss-of-function variations in the HHT causative genes, ENG and ACVRL1, have been described in dermal telangiectasias. It is unclear if somatic second-hit mutations also cause the formation of AVMs and nasal telangiectasias in HHT. To investigate the genetic mechanism of AVM formation in HHT, we evaluated multiple affected tissues from fourteen individuals. DNA was extracted from fresh/frozen tissue of 15 nasal telangiectasia, 4 dermal telangiectasia, and 9 normal control tissue biopsies, from nine unrelated individuals with HHT. DNA from six formalin-fixed paraffin-embedded (FFPE) AVM tissues (brain, lung, liver, and gallbladder) from five individuals was evaluated. A 736 vascular malformation and cancer gene next-generation sequencing (NGS) panel was used to evaluate these tissues down to 1% somatic mosaicism. Somatic second-hit mutations were identified in three in four AVM biopsies (75%) or half of the FFPE (50%) samples, including the loss of heterozygosity in ENG in one brain AVM sample, in which the germline mutation occurred in a different allele than a nearby somatic mutation (both are loss-of-function mutations). Eight of nine (88.9%) patients in whom telangiectasia tissues were evaluated had a somatic mutation ranging from 0.68 to 1.96% in the same gene with the germline mutation. Six of fifteen (40%) nasal and two of four (50%) dermal telangiectasia had a detectable somatic second hit. Additional low-level somatic mutations in other genes were identified in several telangiectasias. This is the first report that nasal telangiectasias and solid organ AVMs in HHT are caused by very-low-level somatic biallelic second-hit mutations.

A 55-year-old woman had remarkably generalized telangiectasia. Large atypical lymphoid cells were found within the lumen of small vessels, and CD20 was positive in her third skin biopsy. She was diagnosed with intravascular large B-cell lymphoma (IVLBCL) and went into remission of the skin manifestations after seven courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) and four courses of intravenous high-dose methotrexate (HD MTX). To our knowledge, this is the first case report of IVLBCL with generalized telangiectasia in China. From a review of the literature, we found that generalized telangiectasia is a remarkable manifestation of intravascular lymphoma, and the differential diagnosis of intravascular lymphoma and panniculitis or vasculitis is very important. When the diagnosis is confusing, multiple skin biopsies are useful.

Hereditary Hemorrhagic Telangiectasia (HHT) is a rare congenital disease in which fragile vascular malformations (VM) - including small telangiectasias and large arteriovenous malformations (AVMs) - focally develop in multiple organs. There are few treatment options and no cure for HHT. Most HHT patients are heterozygous for loss-of-function mutations affecting Endoglin (ENG) or Alk1 (ACVRL1); however, why loss of these genes manifests as VMs remains poorly understood. To complement ongoing work in animal models, we have developed a fully human, cell-based microphysiological model based on our Vascularized Micro-organ (VMO) platform (the HHT-VMO) that recapitulates HHT patient VMs. Using inducible ACVRL1 -knockdown, we control timing and extent of endogenous Alk1 expression in primary human endothelial cells (EC). Resulting HHT-VMO VMs develop over several days. Interestingly, in chimera experiments AVM-like lesions can be comprised of both Alk1-intact and Alk1-deficient EC, suggesting possible cell non-autonomous effects. Single cell RNA sequencing data are consistent with microvessel pruning/regression as contributing to AVM formation, while loss of PDGFB implicates mural cell recruitment. Finally, lesion formation is blocked by the VEGFR inhibitor pazopanib, mirroring positive effects of this drug in patients. In summary, we have developed a novel HHT-on-a-chip model that faithfully reproduces HHT patient lesions and that can be used to better understand HHT disease biology and identify potential new HHT drugs.

To investigate the efficacy of Fractional Radiofrequency Microneedling (FRM) in treating corticosteroid-induced facial erythema.
A retrospective study was conducted involving eight patients diagnosed as corticosteroid-induced facial erythema. Each patient underwent a single session of FRM. Evaluative measures included Clinician\'s Erythema Assessment (CEA), Patient\'s Self-Assessment (PSA), assessment of telangiectasia severity, procedure-associated pain (10-point scale), patient satisfaction (3-point scale) and secondary outcomes.
The study found a 75% success rate and 100% effectiveness rate in alleviating erythema symptoms. CEA and PSA scores decreased by 67.7% and 78.1%, respectively. No cases of erythema rebound were recorded during the 3-month follow-up period.
FRM demonstrated effectiveness and safety in treating facial erythema, offering promising advancement in dermatologic therapeutics.

Telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly (TEBC) syndrome is a rare autosomal dominant condition, recently linked to the protein kinase D1 (PRKD1) gene. The phenotype of TEBC remains incomplete at this point. Our aim is to improve the characterization of the clinical and molecular aspects of the TEBC syndrome. We report on the 8th patient carrying a heterozygous de novo variation of PRKD1 c.2134G > A, p. (Val712Met) identified by trio exome sequencing. The proband presents with partial atrioventricular septal defect, brachydactyly, ectodermal dysplasia, telangiectasia that developed in childhood, intellectual disability with microcephaly, multicystic renal dysplasia and moderate hormonal resistance. In view of this 8th description and review of the literature, it appears that neurodevelopmental disorders and microcephaly are frequently associated with PRKD1 missense variants, adding to the four main clinical signs described initially in the TEBC syndrome. Further descriptions are required to confirm the observed endocrine and kidney abnormalities. This should contribute to a more comprehensive understanding of the phenotypic spectrum and may help establish genotype-phenotype correlations. In the context of genotype-first strategy, accurate patient descriptions are fundamental. Characterization of specific syndromic associations is essential for variant interpretation support and patient follow-up, even in very rare diseases, such as the TEBC syndrome.

Intravascular large B-cell lymphoma (IVLBCL) is a rare type of extranodal, diffuse, large B-cell lymphoma characterized by the selective growth of lymphoma cells within the lumen of small blood vessels, with no lymphadenopathy or masses. Herein, we report a cutaneous variant of IVLBCL that is rare in Asia. A healthy 73-year-old Japanese woman presented to our hospital with painful erythematous indurations and telangiectasia of the lower extremities, which was confirmed on dermoscopy. Physical examination revealed no systemic involvement, and laboratory parameters were within normal ranges. No abnormal fluorodeoxyglucose (FDG) uptake was detected on 18FDG positron emission tomography/computed tomography. Histopathological examination revealed proliferation and dilatation of blood vessels in the subcutis layer, occluded by CD20-positive atypical lymphoid cells. Thus, the patient was diagnosed with a cutaneous variant of IVLBCL without systemic symptoms. In conclusion, it is important to confirm telangiectasia using dermoscopy and perform skin biopsies in patients presenting with sudden-onset erythematous induration.

OBJECTIVE: The purpose of this study was to compare ultra-low dose (ULD) and standard low-dose (SLD) chest computed tomography (CT) in terms of radiation exposure, image quality and diagnostic value for diagnosing pulmonary arteriovenous malformation (AVM) in patients with hereditary hemorrhagic telangiectasia (HHT).
METHODS: In this prospective board-approved study consecutive patients with HHT referred to a reference center for screening and/or follow-up chest CT examination were prospectively included from December 2020 to January 2022. Patients underwent two consecutive non-contrast chest CTs without dose modulation (i.e., one ULD protocol [80 kVp or 100 kVp, CTDIvol of 0.3 mGy or 0.6 mGy] and one SLD protocol [140 kVp, CTDIvol of 1.3 mGy]). Objective image noises measured at the level of tracheal carina were compared between the two protocols. Overall image quality and diagnostic confidence were scored on a 4-point Likert scale (1 = insufficient to 4 = excellent). Sensitivity, specificity, positive predictive value and negative predictive value of ULD CT for diagnosing pulmonary AVM with a feeding artery of over 2 mm in diameter were calculated along with their 95% confidence intervals (CI) using SLD images as the standard of reference.
RESULTS: A total of 44 consecutive patients with HHT (31 women; mean age, 42 ± 16 [standard deviation (SD)] years; body mass index, 23.2 ± 4.5 [SD] kg/m2) were included. Thirty-four pulmonary AVMs with a feeding artery of over 2 mm in diameter were found with SLD images versus 35 with ULD images. Sensitivity, specificity, predictive positive value, and predictive negative value of ULD CT for the diagnosis of PAVM were 100% (34/34; 95% CI: 90-100), 96% (18/19; 95% CI: 74-100), 97% (34/35; 95% CI: 85-100) and 100% (18/18; 95% CI: 81-100), respectively. A significant difference in diagnostic confidence scores was found between ULD (3.8 ± 0.4 [SD]) and SLD (3.9 ± 0.1 [SD]) CT images (P = 0.03). No differences in overall image quality scores were found between ULD CT examinations (3.9 ± 0.2 [SD]) and SLD (4 ± 0 [SD]) CT examinations (P = 0.77). Effective radiation dose decreased significantly by 78.8% with ULD protocol, with no significant differences in noise values between ULD CT images (16.7 ± 5.0 [SD] HU) and SLD images (17.7 ± 6.6 [SD] HU) (P = 0.07).
CONCLUSIONS: ULD chest CT provides 100% sensitivity and 96% specificity for the diagnosis of treatable pulmonary AVM with a feeding artery of over 2 mm in diameter, leading to a 78.8% dose-saving compared with a standard low-dose protocol.

BACKGROUND: Pulsed-dye lasers (PDL) are one of the standard therapies for rosacea, but alternatives are needed.
OBJECTIVE: To compare the efficacy and safety of the variable-sequenced, large-spot 532 nm KTP laser to the 595 nm PDL in treating rosacea.
METHODS: A prospective, controlled, evaluator-blinded study. Patients were treated with either a KTP or PDL with 1-3 sessions at intervals of 6-8 weeks. A follow-up visit was scheduled on Week 6 post-treatment. Clinical outcome was assessed by computer-assisted analysis and by patients and two blinded dermatologists. Pain intensity during treatment and adverse events were documented.
RESULTS: Forty-five patients (mean age 51 years) were allocated in a 2:1 ratio to either the KTP or PDL. Erythema in both treatment arms decreased significantly (p < 0.01). Clinical evaluation revealed high improvement. Mean pain intensity was significantly lower with the KTP (2.5/10) than with the PDL (4.1/10). Both lasers showed a good safety profile. Relevant purpura was only seen in the PDL group.
CONCLUSIONS: Both the variable-sequenced, large-spot KTP and the PDL demonstrated comparable efficacy in treatment of rosacea. Regarding safety, the KTP exhibited fewer post-treatment reactions. The KTP might serve as a potential alternative to PDL in the treatment of rosacea.

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