Hypotrichosis-lymphedema-telangiectasia syndrome: Report of ileal atresia associated with a SOX18 de novo pathogenic variant and review of the phenotypic spectrum.

Hypotrichosis-lymphedema-telangiectasia syndrome (HLTS) is a rare condition caused by pathogenic variants in the SOX18 gene. SOX18 plays a key role in angio- and lymphangiogenesis due to its expression in venous endothelial cells from which the lymphatic system develops. It is also expressed in embryonic hair follicles, heart, and vascular smooth muscle cells. The main clinical symptoms of HLTS include sparse hair, alopecia totalis, lymphedema, most often affecting lower limbs, and telangiectatic lesions. Only 10 patients with a SOX18 pathogenic variant have been described that presented with additional features such as hydrocele, renal failure, arterial or pulmonary hypertension, aortic dilatation, and facial dysmorphism. Here, we summarize these phenotypic variations and report an additional HLTS patient, with a 14-nucleotide de novo duplication in SOX18 and congenital ileal atresia, a feature not previously associated with HLTS.

Clinical and neuroimaging findings in 33 patients with MCAP syndrome: A survey to evaluate relevant endpoints for future clinical trials.

Megalencephaly-CApillary malformation-Polymicrogyria (MCAP) syndrome results from somatic mosaic gain-of-function variants in PIK3CA. Main features are macrocephaly, somatic overgrowth, cutaneous vascular malformations, connective tissue dysplasia, neurodevelopmental delay, and brain anomalies. The objectives of this study were to describe the clinical and radiological features of MCAP, to suggest relevant clinical endpoints applicable in future trials of targeted drug therapy. Based on a French collaboration, we collected clinical features of 33 patients (21 females, 12 males, median age of 9.9 years) with MCAP carrying mosaic PIK3CA pathogenic variants. MRI images were reviewed for 21 patients. The main clinical features reported were macrocephaly at birth (20/31), postnatal macrocephaly (31/32), body/facial asymmetry (21/33), cutaneous capillary malformations (naevus flammeus 28/33, cutis marmorata 17/33). Intellectual disability was present in 15 patients. Among the MRI images reviewed, the neuroimaging findings were megalencephaly (20/21), thickening of corpus callosum (16/21), Chiari malformation (12/21), ventriculomegaly/hydrocephaly (10/21), cerebral asymmetry (6/21) and polymicrogyria (2/21). This study confirms the main known clinical features that defines MCAP syndrome. Taking into account the phenotypic heterogeneity in MCAP patients, in the context of emerging clinical trials, we suggest that patients should be evaluated based on the main neurocognitive expression on each patient.

Clinical outcome of short-term compression after sclerotherapy for telangiectatic varicose veins.

BACKGROUND: Sclerotherapy is considered to be the method of choice for the treatment of telangiectatic varicose veins (C1 veins). Whereas the use of compression stockings after sclerotherapy is recommended, little is known about the impact of compression on the outcome of sclerotherapy. The aim of this study was to assess the influence of compression on the outcome of injection sclerotherapy of C1 varicose veins. METHODS: There were 100 legs of 50 consecutive patients with chronic venous insufficiency (C1) included. After randomization per patient, both legs were treated with sclerotherapy in a predefined area of the thigh (measuring 100 cm2), followed by eccentric compression for 24 hours. Group A received no further compression, whereas group B was additionally equipped with compression stockings of 18 to 20 mm Hg above the ankle and continued wearing these for 1 week. Photodocumentation was performed before, 1 week after, and 4 weeks after sclerotherapy, and the clinical outcome was assessed at these postprocedure follow-up dates. The photographs were reviewed by an internal unblinded rater and an independent blinded external rater. RESULTS: There was no discernible difference between the groups in terms of clinical outcome or side effects after 4 weeks. Whereas inter-rater reliability was high, there was no correlation between the raters and patients in terms of outcome. In 55% of the treated legs, the patients deemed the result of the treatment to be good; in 27% of the treated legs, fair; and in 18%, poor. Postprocedure hyperpigmentation occurred in 13% of patients and was comparable in both groups. Compression therapy was found to be comfortable by the majority (58%) of patients. CONCLUSIONS: One week of postinterventional compression therapy had no clinical benefit compared with no compression.

Effect of 808-nm Laser Photobiomodulation Treatment in Blepharitis Rat Model.

PURPOSE: Blepharitis, simply defined as eyelid inflammation, is one of the common ocular conditions associated with discomfort and irritation. Because blepharitis causes meibomian gland dysfunction and dry eye, this study aimed to confirm the effect of photobiomodulation (PBM) on blepharitis. METHODS: A total of 20 rats were randomly assigned to 4 equal groups, including control, blepharitis, PBM, and eye drop. Blepharitis was induced in rats by injecting complete Freund's adjuvant in the eyelid margins. PBM intervention was given every 3 days after blepharitis induction. Clinical signs including tear volume, tear breakup time (TBUT), meibomian gland swelling, fluorescein, telangiectasia, and meibomian gland secretion scores were measured every week, and the rats were killed for histological analysis after 4 weeks. Immunohistochemistry was performed to compare the level of inflammatory cytokines, interleukin-1ß and tumor necrosis factor-α, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining on retina was performed to observe any retinal damage. RESULTS: Tear volume and TBUT increased with PBM intervention, and with improved eyelid swelling, corneal staining, telangiectasia, and meibomian gland secretion scores increased. Hematoxylin and eosin staining showed no structural abnormalities of meibomian gland caused by blepharitis induction. Immunohistochemistry revealed that the levels of inflammatory cytokines interleukin-1ß and tumor necrosis factor-α were lowered with PBM treatment in both eyelid and conjunctiva. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed no retinal damage. CONCLUSIONS: Laser PBM at 808 nm was effective in alleviating ocular signs and controlling inflammation in blepharitis rat model. The in vivo results suggest that PBM has the potential to be used in treating blepharitis patients.

Initiation of reticular and spider veins, incompetent perforantes and varicose veins in the saphenous vein network of the rat.

In an attempt to induce experimental varicosity, reverse perforant vein development was initiated in the rat leg by applying a chronic (14 and 32 weeks) partial stricture on the main branch of the deep femoral vein. At surfacing of the incompetent perforantes, typical reticular vein plaques and spider veins were identified by video-microscopy and quantitative histology. Deep vein blood was channeled by them into the saphenous vein system, the extra flow deforming these vessels, causing local dilations and broken course, even undulations of larger branches.

Ataxia pancytopenia syndrome due to SAMD9L mutation presenting as demyelinating neuropathy.

Ataxia pancytopenia (ATXPC) syndrome due to gain-of-function pathogenic variants in the SAMD9L gene has been described in 38 patients to date. It is characterized by variable neurological and hematological phenotypes including ataxia, pyramidal signs, cytopenias, and hematological malignancies. Peripheral neuropathy with slowing of conduction velocities has been reported in only two affected individuals. We describe a female with childhood onset neuropathy diagnosed as Charcot-Marie-Tooth disease type 1 with onset of cerebellar ataxia in her 50s. Cerebellar, pyramidal, and neuropathic features were found on examination. Additionally, she also had conjunctival telangiectasia. Nerve conduction studies confirmed a demyelinating neuropathy. MRI brain showed cerebellar atrophy with diffuse white matter hyperintensities. OCT demonstrated global thinning of the retinal nerve fiber layer (RNFL). Full blood count has always been normal. A previously described pathogenic variant in SAMD9L [c.2956C>T p.(Arg986Cys)] was identified on whole exome sequencing. This case extends the previously described phenotype to include conjunctival telangiectasia and RNFL thinning and suggests that ATXPC syndrome should be considered in the differential for inherited demyelinating neuropathies.

Telangiectatic Carcinoma - Like Lymphangioma Circumscriptum. A Rare Form of Cutaneous Metastasis of Breast Carcinoma: Case Report.

INTRODUCTION: The Breast cancer is the most common malignancy in middle-aged women and that causes skin metastasis. Skin metastasis in internal cancer cases is a very rare condition and may be difficult to diagnose and have poor prognostic marker. Cutaneous metastasis of breast carcinoma is mostly seen as direct invasion and/or local infiltration. However, in addition to the well-known types, cutaneous metastases may mimic many benign skin lesions and therefore may be difficult to diagnose. CASE REPORT: In this article we present a 36-year-old woman with telangiectatic carcinoma-like lymphangioma circumscriptum, a rare form of cutaneous metastasis skin metastases. It can be the first sign of internal malignancies, so early diagnosis is very important at this stage. CONCLUSION: Therefore, solitary lesions or benign dermatoses seen in the skin and not associated with specific disease should be considered as tumor metastasis especially in female patients with a history of breast cancer and differential diagnosis must be made.

Colonic Manifestations and Complications Are Relatively Under-Reported in Systemic Sclerosis: A Systematic Review.

OBJECTIVES: Although systemic sclerosis (SSc) is known to affect the gastrointestinal (GI) tract, most of the literature focuses on esophageal, small intestinal, or anorectal manifestations. There have been no reviews focused on large bowel SSc complications in over 30 years. The aim of this study is to perform a systematic review of colonic manifestations and complications of SSc. METHODS: An experienced librarian conducted a search of databases, including English and Spanish articles. The search used keywords including "systemic sclerosis," "scleroderma," and "colon." A systematic review was performed using Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Case reports/series were screened for validity by adapting from criteria published elsewhere. RESULTS: Of 1,890 articles, 74 met selection criteria. Fifty-nine of the 77 articles were case reports/series. The most common article topics on colonic SSc complications were constipation/dysmotility (15), colonic volvulus (8), inflammatory bowel disease (7), microscopic colitis (6), megacolon (6), and telangiectasia (6). Colonic manifestations constituted 24% of articles on GI complications of SSc. There were a total of 85 cases (84% women, with a median age of onset of colon complication of 52 years). Limited cutaneous SSc phenotype (65.6%) was more common than diffuse (26.2%). Patients frequently had poor outcomes with high mortality related to colonic complications (27%). Recent studies explore contemporary topics such as the microbiome in SSc and prucalopride for chronic constipation in SSc. DISCUSSION: Colonic complications comprise a large proportion of the published reports on GI symptoms afflicting patients with SSc and require raised diagnostic suspicion and deliberate action to avoid potentially serious complications including death.

Gastrointestinal Vascular Malformations in Patients with Turner's Syndrome: A Systematic Review of Case Reports.

BACKGROUND/AIM: There is a paucity of data on gastrointestinal (GI) vascular abnormalities in patients with Turner's syndrome (TS). Therefore, this literature review aimed to characterize the nature of GI vascular malformations in patients with TS, their localization in the GI tract, and their clinical and laboratory manifestations. METHODS: A systematic search for articles was conducted using Medline and Embase (until August 2017). A manual search of the references of the included papers was performed to identify any potential additional references. We also conducted a retrospective chart review of all patients with TS and GI bleeding who were hospitalized at our institution. RESULTS: A total of 29 articles published between 1947 and 2015 that described 39 cases were reviewed. Additionally, we included 2 patients who were hospitalized at our institution. The median age of patients with TS was 15 years (range: 0.1-57 years). Iron deficiency anaemia (35/40), haematochezia (15/37), and melaena (14/36) were the most common symptoms. Abnormal GI vessels occurred throughout the entire bowel, with a predilection for the small intestine (72%, 29/40). The most common abnormal vessels (65%, 24/37) were telangiectasias and dilated veins. CONCLUSION: Telangiectasias and dilated veins of the small intestine were the most commonly seen abnormal GI vessels in patients with TS.

Whole-Body Distribution and Clinical Association of Telangiectases in Systemic Sclerosis.

Importance: In systemic sclerosis (SSc), to date, no study has precisely described the total number and fine distribution of telangiectases (TAs), their clinical association with the disease, and the biological mechanisms causing their development. Objectives: To describe the whole-body distribution of TAs and assess the association between the whole-body TA number and the characteristics of patients with SSc. Design, Setting, and Participants: A single-center, cross-sectional study was conducted between July 11, 2016, and March 15, 2017, at the National Referral Centre for Rare Systemic and Autoimmune Diseases in France. A population-based sample of 106 adults who fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria for SSc were included; 8 patients who had previously received laser treatment for TAs were excluded. Main Outcomes and Measures: The number of TAs on the whole body (total and those >5 mm) and TA distribution in different areas were recorded. The association with clinical and biological data was studied using univariate and multivariate linear regression. Results: A total of 106 patients (83 [78.3%] women) were enrolled, including 12 with precapillary pulmonary hypertension (PH). Mean (SD) age was 60.6 (13.5) years. Telangiectasia distribution was 37.2% on the face, 33.2% on the upper limbs, including 26.4% on the hands, 28.1% on the trunk, including 17.1% for the upper part of the trunk, and 1.5% on the lower limbs. In analysis using the multivariate linear regression model, the whole-body TA number was independently associated with male sex (percentage change, 144.4%; 95% CI, 7.5% to 455.9%; P = .03), PH (162.8%; 95% CI, 5.6% to 553.8%; P = .04), history of pulmonary embolism (336.4%; 95% CI, 39.0% to 1270.1%; P = .01), glomerular filtration rate (-1.6%; 95% CI, -3.2% to -0.1% per 1-mL/min/1.73 m2 increase; P = .04), and soluble endoglin level (28.2%; 95% CI, 1.2% to 62.5% per 1-ng/mL increase; P = .04). Receiver operating characteristic analyses assessing the ability of TAs to identify the presence of PH revealed that the area under the curve was significant for the TA number on the whole body (0.77; 95% CI, 0.57 to 0.88), on the hands and face (0.81; 95% CI, 0.57 to 0.91), and on the hands (95% CI, 0.77; 95% CI, 0.57 to 0.89). Conclusions and Relevance: In the patients in this study with SSc, TAs were predominantly located on the face, hands, and the upper part of the trunk. Telangiectases appeared to be associated with vasculopathy features of SSc, particularly with PH and soluble endoglin levels.

Pathophysiology of telangiectasias of the lower legs and its therapeutic implication: A systematic review.

Objective Telangiectasias of the lower legs are intradermal dilatations of the subpapillary venous plexus, but their pathophysiology and risk factors are still largely unknown. The purpose of this review is to summarize the current knowledge on the pathophysiology and risk factors for telangiectasias. Methods A systematic review of the literature indexed in Medline completed with textbooks and European phlebology journals from the French, Swiss, and German phlebology societies was performed. Results A multitude of risk factors and several pathophysiological hypotheses, such as reflux, arterio-venous micro-shunts, parietal, and connective tissue abnormalities, are described in the literature. The different hypotheses are discussed and put in a clinical perspective, in particular their therapeutic implications for phlebologists. Conclusion In conclusion, pathophysiology and risk factors of telangiectasias are still largely unknown, and a better understanding could improve treatment results and reduce recurrence.

Cutis marmorata telangiectatica congenita and major lower limb asymmetry.

A 39-week-old male newborn presented at birth with atrophic erythematous and purpuric skin lesions, in a typical right-sided segmental distribution. Lesions were persistent and unaffected by rewarming in the postpartum period. Postnatal echocardiogram showed a predominance of the right cavities and an upper atrial septal defect. Cerebral and abdominal ultrasound were normal along with ophthalmological examination. On follow-up, lower limbs asymmetry was noted. The right lower limb was shorter in length and had a smaller diameter. At 6 months, the right lower limb was 1.5 cm shorter than the left, most likely related to nutritive vessels malformations. The discrepancy was even more pronounced at the age of 9 months. This leg-length asymmetry can lead to severe functional limitations in the future.

Quantification of early cutaneous manifestations of chronic venous insufficiency by automated analysis of photographic images: Feasibility and technical considerations.

We postulate that blue telangiectasia and brownish pigmentation at ankle level, early markers of chronic venous insufficiency, can be quantified for longitudinal studies of chronic venous disease in Caucasian people. Objectives and methods To describe a photographic technique specially developed for this purpose. The pictures were acquired using a dedicated photo stand to position the foot in a reproducible way, with a normalized lighting and acquisition protocol. The image analysis was performed with a tool developed using algorithms optimized to detect and quantify blue telangiectasia and brownish pigmentation and their relative surface in the region of interest. To test the short-term reproducibility of the measures. Results The quantification of the blue telangiectasia and of the brownish pigmentation using an automated digital photo analysis is feasible. The short-term reproducibility is good for blue telangiectasia quantification. It is a less accurate for the brownish pigmentation. Conclusion The blue telangiectasia of the corona phlebectatica and the ankle flare can be assessed using a clinimetric approach based on the automated digital photo analysis.

A sonographic study of thigh telangiectasias.

Introduction To date, there are limited descriptive data on the ultrasonographic characteristics of reticular and perforator veins associated with telangiectasias of the thigh. Objectives Evaluate the prevalence, anatomic correlations of reticular and perforator veins associated with lateral thigh telangiectasias. Methods This was a cohort study performed between June and December of 2014. Twenty-four female patients (43 limbs) with telangiectasias of the lateral thigh were evaluated by duplex ultrasound. Reticular and perforator veins were characterized according to valvular competency, vein diameter and connection with perforator veins at the thigh. Body mass index, current use of oral contraceptive, and history of pregnancy correlation data were also collected. A non-parametric Kruskal-Wallis test and a Student's t-test test were used for analysis. Results All 43 limbs had incompetent reticular veins underlying telangiectasias sites. A total of 20 incompetent perforator veins were found to be connected to the reticular veins. Obese and overweight patients had a higher prevalence of incompetent perforator veins and larger reticular veins when compared to those with normal weight (P < 0.05). Lower extremities with telangiectasias had a higher frequency of total perforator veins (n = 33) and incompetent perforator veins (n = 16) than extremities without telangiectasias (p = 0.001). Conclusion Lateral thigh telangiectasias were associated with both incompetent reticular and perforator veins. Obese and overweight patients were especially affected.

Vasculopatía colágena cutánea: una causa infrecuente de telangiectasias generalizadas / Cutaneous collagenous vasculopathy: A rare cause of generalized cutaneous telangiectasia

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[Adjuvant phlebotrophic therapy and its effect on anti-inflammatory response after sclerotherapy]. / Ad'yuvantnaya flebotropnaya terapiya i ee vliyanie na provospalitel'nyi otvet posle skleroterapii.

The study was aimed at evaluating the degree of the systemic and local inflammatory reaction after sclerotherapy, as well as the effect of micronized purified flavonoid fraction (Detralex) thereupon. The study comprised a total of 60 female patients presenting with reticular veins and telangiectasias (clinical class C1 according to the CEAP classification). The patients were subdivided into two groups, each comprising 30 women. The Study Group patients two weeks prior to the forthcoming sclerotherapy had been taking Detralex prescribed at a daily dose of 1,000 mg whose administration was prolonged by not less than 2 months after the procedure. The Control Group patients received no drug. We determined the systemic and local levels of inflammatory markers, anti-inflammatory cytokines and growth factors: C-reactive protein in a highly sensitive range, histamine, interleukin-1, tumour necrosis factor alpha and vascular endothelial growth factor. Patients in the Study and Control Groups on day 10 after sclerotherapy demonstrated a considerable increase in the levels of anti-inflammatory cytokines and inflammatory markers. At the same time, excess of the baseline levels of the parameters in patients taking Detralex was statistically significantly lower as compared with the Control Group patients: C-reactive protein - 6.0±0.9 mg/l vs 8.3±1.0 mg/l; histamine - 87.0±9.8 µg/l vs 156.9±33.9 µg/l; interleukin-1 - 5.9±0.4 pg/ml vs7.6±0.6 pg/ml; tumour necrosis factor alpha - 5.9±0.9 pg/ml vs 7.5±0.4 pg/ml; vascular endothelial growth factor - 252.3±26.0 pg/ml vs 325.1±47.7 pg/ml. A conclusion was made that microsclerotherapy with the use of low-concentration detergent drugs was accompanied by a local vein-specific inflammatory reaction whose degree may be diminished by means of prescribing micronized purified flavonoid fraction (Detralex) two weeks prior to and during the whole subsequent period of phlebosclerosing treatment in a standard daily dose of 1,000 mg.