Defining the transcriptome of PIK3CA-altered cells in a human capillary malformation using single cell long-read sequencing.

PIK3CA-related overgrowth spectrum (PROS) disorders are caused by somatic mosaic variants that result in constitutive activation of the phosphatidylinositol-3-kinase/AKT/mTOR pathway. Promising responses to molecularly targeted therapy have been reported, although identification of an appropriate agent can be hampered by the mosaic nature and corresponding low variant allele frequency of the causal variant. Moreover, our understanding of the molecular consequences of these variants-for example how they affect gene expression profiles-remains limited. Here we describe in vitro expansion of a human capillary malformation followed by molecular characterization using exome sequencing, single cell gene expression, and targeted long-read single cell RNA-sequencing in a patient with clinical features consistent with Megalencephaly-Capillary Malformation Syndrome (MCAP, a PROS condition). These approaches identified a targetable PIK3CA variant with expression restricted to PAX3+ fibroblast and undifferentiated keratinocyte populations. This study highlights the innovative combination of next-generation single cell sequencing methods to better understand unique transcriptomic profiles and cell types associated with MCAP, revealing molecular intricacies of this genetic syndrome.

Telangiectasia Macularis Multiplex Acquisita and its Potential Association with Calcium Channel Blockers: A Retrospective Study of 46 Chinese Patients.

Telangiectasia macularis multiplex acquisita is an acquired cutaneous telangiectasis of unknown aetiology, and it lacks both effective and cost-efficient treatment. This study aims to identify a novel potential associated factor of the disease and explore feasible therapeutic interventions. In this retrospective case series study, 46 Chinese patients diagnosed with telangiectasia macularis multiplex acquisita between 1 January 2007 and 18 May 2023 were included. The median age of onset was 43 years (23 to 60 years), and the male to female ratio was 10.5:1. Besides previously reported associations including chronic liver disorders, alcohol consumption, and smoking, a potential association was found between use of calcium channel blockers and development of telangiectasia macularis multiplex acquisita. Twenty-two of 27 hypertensive patients took calcium channel blockers, with 17 followed up. Ten out of 17 displayed a range of improvements following the cessation of calcium channel blockers; 1 patient reported no lesion change post-discontinuation of calcium channel blockers; 1 patient continued their medication but showed partial improvement after 2 pulsed dye laser treatments; 1 patient observed lesion colour lightening without altering hypertensive medication or other specific treatments; and another 4 kept their previous hypertensive regimen due to blood pressure stability concerns, with no change in their lesions. The study proposes that cessation of calcium channel blockers can be a novel therapeutic approach for affected individuals.

Intra-abdominal telangiectatic osteosarcoma: a case report.

BACKGROUND: Telangiectatic osteosarcoma is rare and it rarely affects flat bones, especially the bones of the pelvis. It is uncommon for telangiectatic osteosarcoma to be considered as a differential diagnosis when assessing a large intrabdominal mass. CASE REPORT: We present our case of a 33-year-old African female who presented with a sizeable telangiectatic osteosarcoma of the left iliac bone. She reported a 3-year duration of a painless, slow-growing mass arising from the left flank. At examination, a large bony hard mass extending from the left ilium to the umbilicus was noted, almost mimicking an intra-abdominal pregnancy. All laboratory tests were within normal limits and an unconventional surgical approach was used for a one-stage excision of the tumor without complications. The definitive histopathological diagnosis postexcision was that of a telangiectatic osteosarcoma only on the second review of the histological specimen. CONCLUSIONS: Pelvic telangiectatic osteosarcoma is rare, and the ilium is the commonly affected pelvic bone. These tumors can be sizeable at presentation with intra-abdominal or pelvic extension with a high chance of misdiagnosis. Fortunately surrounding soft tissue involvement seems to be a rare and late finding when present.

Telangiectatic osteosarcoma of the mandible-A rare case report and an insight into differential diagnosis.

Telangiectatic osteosarcoma (TOS) is a rare variant of osteosarcoma that typically affects young individuals and long bones. The case under discussion was seen in the mandible of a 57-year-old female and had rapidly grown in size within a week. Microscopically, the tumour was characterised by large vascular cavities surrounded by anaplastic cells. Thin lacy tumour osteoid was observed at various foci. Abundant multinucleated osteoclastic giant cells along with areas of necrosis were also noted. The tumour cells were positive for SATB2, while negative for Cytokeratin AE1/3, CD 34. Ki-67 positivity was observed in more than 50% of tumour cells. A diagnosis of high grade telangiectatic osteosarcoma was thus made.

Investigation of the Genetic Determinants of Telangiectasia and Solid Organ Arteriovenous Malformation Formation in Hereditary Hemorrhagic Telangiectasia (HHT).

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.

Efficacy of fractional radiofrequency in the treatment of erythematous capillary rosacea: A split-face study.

OBJECTIVE: To assess the effectiveness and safety of treating erythematotelangiectatic rosacea using fractional radiofrequency (FRF). METHODS: Twenty patients with a confirmed diagnosis of erythema capillaris rosacea were selected, and one side of each patient's face was randomly assigned to receive FRF treatments for three to six times, with an interval of 2 weeks between each treatment. VISIA, dermoscopy, and the Clinician's Erythema Evaluation Scale (CEA) were applied to evaluate the efficacy of the treatment before and after the treatment, to record the VAS scores and adverse reactions, and to conduct a patient satisfaction survey. RESULTS: The characteristic counts and scores of red zone and porphyrin as assessed by VISIA test were significantly decreased, and the difference between the treated side and the pretreatment side was statistically significant (p < 0.05), and the efficacy of the treatment was statistically insignificant compared with the control side, except for the red zone and porphyrin which were statistically significant before and after the treatment (p > 0.05). By CEA score, the difference between the treated side after treatment and the control side was statistically significant (p < 0.05), and the difference between the treated side before and after treatment was statistically significant (p < 0.05); the difference between the control side before and after treatment was not statistically significant (p > 0.05). Dermatoscopic observation showed reduction in pore size, reduction of yellowish-white and black horn plugs within the pores, lightening of the red background and thinning and blurring of the capillary structure on the treated side of the skin compared to the control side, and the skin on the treated side showed the above mentioned changes before and after the treatment as well. The mean pain score of the subjects was obtained by VAS score 3.67 ± 0.90. Adverse effects included mild edema, erythema, and microscopic crusting; no long-term adverse effects were seen in all patients. The efficacy of FRF treatment was evaluated 1 month after the final treatment, and 85% of the subjects rated it as satisfactory, very satisfactory, and very satisfactory. CONCLUSION: FRF for the treatment of erythematous capillary dilatation rosacea is effective, safe, and suitable for clinical promotion.

Treatment of telangiectasias with a 595-nm pulsed dye laser following hemangioma involution: a retrospective analysis.

Telangiectasias are the most frequent type of sequelae of infantile hemangiomas after involution. Few studies have reported the treatment of telangiectasias with 595-nm pulsed dye lasers. Therefore, the objective of this study was to assess the efficacy and safety of a 595-nm pulsed dye laser for treating residual telangiectasias following hemangioma involution. This is a retrospective case series that analyzes the medical records and reviews the charts of 22 patients who had undergone 595-nm pulsed dye laser treatment for residual telangiectasias. Pre- and post-treatment digital images were independently assessed, and the changes were scored to ascertain the efficacy of the treatment (0 = no change, 4 = complete improvement). Of the 22 patients, 59.1% experienced complete resolution of telangiectasias following treatment. No serious complications or side effects were reported. The observations indicate that the 595-nm pulsed dye laser is effective and safe for treating residual telangiectasias following hemangioma involution.

Combination Foam and Liquid Sclerotherapy for Lower Extremity Reticular and Telangiectatic Veins: A Single-Center Retrospective Study.

BACKGROUND: Lower extremity reticular and telangiectatic veins are of common cosmetic concern. OBJECTIVE: To retrospectively evaluate results of lower extremity sclerotherapy using a combination of foam and liquid sclerosing agents. METHODS: A retrospective chart review of sclerotherapy patients at a dermatology practice (January 2014 to April 2023) was performed. RESULTS: Eight hundred and nine patients (775 women and 34 men) with a mean age of 49.6 ± 12.2 (18-84) years underwent a mean 1.4 ± 0.7 (1-7) sessions. Multiple different sclerosing agents were used, with 0.2% sodium tetradecyl sulfate foam/liquid predominating, although 72% glycerin liquid and 0.25% to 0.5% polidocanol foam/liquid were also used. Coagula occurred in 61.0% of patients at 2 weeks and 6.4% at 3 months, whereas postsclerotherapy hyperpigmentation was seen in 5.0% and 19.1% of patients at the same time points. Both were more common after first-round treatment, each with a trend toward decreased frequency with increasing session number. Telangiectatic matting was found in 2.3% of 3-month follow-up patients. Edema, superficial venous thrombophlebitis, migraines, and ulceration were rarely seen. Significant clinical improvement was noted in 72.0% of treatments. CONCLUSION: This retrospective chart review, the largest to date of its kind, confirms the safety and efficacy of cosmetic lower extremity sclerotherapy with a combination of foam and liquid sclerosing agents.

Retinal abnormalities in a patient with cutis marmorata telangiectatica congenita.

Cutis marmorata telangiectatica congenita is a rare congenital vascular malformation characterised by cutaneous vascular abnormalities, typically diagnosed at birth or in the early postnatal period. Although typically benign, this disease is associated with other systemic abnormalities, including rare ocular alterations, such as congenital glaucoma, cataracts and retinopathy.This manuscript describes a female infant, who presented with generalised livedo reticularis, a band of alopecia and cutaneous atrophy in the temporal region above the coronal suture. The patient was diagnosed with cutis marmorata telangiectatica congenita by a paediatrician, and an ophthalmological evaluation was requested. A funduscopy examination in both eyes showed temporal and superior retina with avascular areas with new vessels, venous dilations and shunts, and no retinal detachments. Given these findings, we performed retinal photocoagulation laser treatment with excellent results.This case report highlights the importance of early ophthalmological evaluation of children with this disease to prevent secondary complications, such as vitreous haemorrhage and tractional retinal detachment.

PRKD1-related telangiectasia-ectodermal dysplasia-brachydactyly-cardiac anomaly syndrome: Case report and review of the literature.

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.

Comparison of dermoscopic characteristics on toenail onychomycosis in psoriatic and non-psoriatic patients: A prospective study.

BACKGROUND: Psoriatic patients may experience the coexistence of onychomycosis (OM). However, the evaluation of OM in psoriatics has been hindered by potential clinical differences from OM in non-psoriatics. OBJECTIVE: To assess and compare dermoscopic features between toenail OM in psoriatic and in non-psoriatic patients. PATIENTS AND METHODS: Between September 2020 and September 2023, dermoscopy was conducted on 183 affected toenails by OM in psoriatics and 232 affected toenails by OM in non-psoriatics in two centres. The dermoscopic characteristics were compared using the Chi-squared test. RESULTS: Among toenail OM cases in psoriatic subjects, the most prevalent dermoscopic features included pitting (147/183, 80.33%) and subungual hyperkeratosis (118/183, 64.48%). Conversely, toenail OM in non-psoriatics was characterized by subungual hyperkeratosis (175/232, 75.43%) and nail spikes (139/232, 59.91%). Comparative analysis revealed a significantly higher occurrence of pitting (80.33% vs. 15.96%, p < .001), periungual telangiectasis (22.40% vs. 4.74%, p < .001), oil patches (12.57% vs. 0.43%,p < .001) and transverse grooves (43.72% vs. 28.45%,p < .01) in toenail OM in psoriatics. Furthermore, toenail OM in psoriatics exhibited a significantly lower frequency of yellow structureless area (13.11% vs. 42.67%, p < .001), nail spikes (43.17% vs. 59.91%, p < .01), ruin appearance of sulphur nugget (8.20% vs. 31.03%, p < .001), dotted/blocky haemorrhage (6.01% vs. 20.69%,p < .001) and partial onycholysis (32.79% vs. 46.98%, p < .01). CONCLUSIONS: Dermoscopic features of toenail OM in psoriatic and non-psoriatic patients exhibit notable differences. OM in psoriatics shows a higher frequency of pitting and periungual telangiectasis, while a lower frequency of yellow structureless areas and nail spikes under dermoscopy.

Cutaneous Collagenous Vasculopathy: A Short Case Series and Literature Review.

ABSTRACT: Cutaneous collagenous vasculopathy (CCV) is a rare and idiopathic microangiopathy of superficial dermal blood vessels. There have been 75 cases described in the literature to date, not including the current report; however, given its clinical similarity to other primary telangiectasias, it is likely to be underreported and underdiagnosed. Here, we describe the clinical and histological features of 2 patients we newly diagnosed with CCV. Both generally fit the profile of prior cases and confirm previously described associations-they both are older White women, have rashes on their lower extremities, and have conditions and medications that are common among other reported cases. However, both are also somewhat atypical, as Patient 1 had symptomatic CCV and Patient 2 had a papular rash. As such, both cases broaden the spectrum of our current understanding of CCV. We also provide a comprehensive review of all published reports of CCV to date and uncover 2 previously unreported associations: one with visceral malignancy, and the other with hypothyroidism. Whether these association are coincidental is worth investigating in future studies.

A comparative study between cryo-laser cryo-sclerotherapy and sclerotherapy in the treatment of telangiectasia and reticular veins: A randomized controlled trial.

OBJECTIVE: Telangiectasias, characterized by dilated venules, are frequently observed in the lower extremities. Sclerotherapy stands out as the predominant treatment of these vascular lesions. The integration of laser therapy with a mild sclerosing agent, serving as an osmotic sclerosant, presents an enhanced cosmetic treatment approach, aiming to optimize outcomes and minimize potential adverse effects. This study sought to evaluate the feasibility, efficacy, and safety of cryo-laser and cryo-sclerotherapy (CLaCS) and compare it with injection sclerotherapy for the treatment of telangiectasia and reticular veins. METHODS: In this randomized controlled trial, individuals expressing concerns about telangiectasia and reticular veins were recruited for aesthetic treatment. The enrolled patients were prospectively randomized according to the chosen treatment technique. Group A included patients undergoing CLaCS with 70% dextrose, focusing on a single area measuring 20 cm by 20 cm. Group B included patients receiving polidocanol injection sclerotherapy for a single area of the same dimensions. RESULTS: Group A comprised 195 patients and group B comprised 197 patients. The rates of complete lesion elimination after the first, second, and third treatment sessions were 64.6%, 86.2%, and 100% in group A and 50.3%, 74.1%, and 85.3% in group B, respectively. Group A exhibited a significantly higher complete elimination rate compared with group B at the conclusion of the study (P < .001). Furthermore, group A demonstrated a statistically significant lower incidence of postprocedural pigmentation and other complications compared with group B (P < .001). These findings underscore the enhanced efficacy and safety profile associated with the CLaCS technique using 70% dextrose compared with injection sclerotherapy with polidocanol. CONCLUSIONS: CLaCS, combining cryo-laser and cryo-sclerotherapy, demonstrated superior efficacy and safety compared with traditional polidocanol sclerotherapy for treating telangiectasia and reticular veins.