Frequency of epistaxis and telangiectasia in patients with hereditary hemorrhagic telangiectasia (HHT) in comparison with the general population: Curaçao diagnostic criteria revisited.

PURPOSE: The Curaçao criteria are well-established diagnostic criteria for hereditary hemorrhagic telangiectasia (HHT), but they lack details regarding a predictive presentation of epistaxis and telangiectasias. This study collects and compares data in HHT and population cohorts to inform the application of these criteria. METHODS: In-person interviews regarding epistaxis and targeted examination for telangiectases in a general population cohort (n = 204) and an HHT cohort (n = 432) were conducted. RESULTS: Frequency of epistaxis, rather than intensity or duration, was the best discriminator of HHT. A cutoff of ≥4 nosebleeds per year alone yielded a diagnostic sensitivity of 97%, and specificity of 84%. The mean number of telangiectases at the sites investigated was 0.4 in the general population cohort and 26.5 in the HHT cohort. The most distinctive sites for telangiectases in HHT were lips and palmar fingers, whereas telangiectases of the face and dorsum of the hand were comparable in both cohorts. CONCLUSION: We propose that the Curaçao criteria be modified to include the following cutoffs: (1) epistaxis frequency of ≥4 nosebleeds per year and (2) telangiectasia count of at least 2 in characteristic locations (palmar aspect of fingers, lips, and oral cavity), and that cutaneous telangiectases at other sites not be considered relevant for diagnostic purposes.

Epidemiology of rosacea in a population-based study of 161,269 German employees.

BACKGROUND: Rosacea is a common chronic skin condition, but data on its epidemiology and related comorbidities are scarce. OBJECTIVES: To analyze the prevalence and associated cutaneous comorbidities of rosacea in Germany. METHODS: Voluntary dermatological full-body examinations were conducted between 2001 and 2016 in more than 500 German companies by experienced dermatologists and documented electronically. Point-prevalence rates were calculated, and associations were tested with chi-squared tests and logistic regression analysis. RESULTS: A total of 161,269 participants (mean age was 43.2 ± 10.9 years; 55.5% male) were included; 2.1% had rosacea (men: 2.1%, women 2.1%, mean age 50.7 ± 9.3 years). The prevalence of rosacea increased significantly with age (16-29 years: 0.3%; 30-39 years: 0.9%; 40-49 years: 2.0%; 50-59 years: 3.5%; 60-70 years: 5.7%). Furthermore, there was a significant decreasing prevalence from skin type I toward type IV (skin type I: 3.2%; II: 2.2%; III: 1.5%; IV: 0.4%). The most frequent dermatological comorbidities were: telangiectasia (OR = 2.5), folliculitis (OR = 1.8), seborrheic dermatitis (OR = 1.6), acne (OR = 1.6), tinea pedis (OR = 1.4), psoriasis (OR = 1.4), spider veins (OR = 1.1), and hemangioma (OR = 1.1). CONCLUSIONS: Rosacea is a common skin condition that is most prevalent above the age of 65 years. Rosacea patients have an increased risk for associated comorbidities. Therefore, the diagnostic and therapeutic process for rosacea patients must ensure an integrated, complete dermatological approach in terms of medical care.

Cutaneous findings in patients with chronic venous insufficiency.

BACKGROUND: Venous hypertension causes many different cutaneous findings such as varicosities, telangiectasia, edema, and pigmentation, dermatitis, and venous ulcers on the skin. OBJECTIVE: This study aims to investigate the cutaneous signs and symptoms of chronic venous insufficiency (CVI) and to examine their contribution to early diagnosis. METHODS: A total of 150 patients were included in the study who applied to the dermatology outpatient clinic and were diagnosed with skin disease related to CVI or had skin findings. Patient's age, gender, complaints, occupation, additional diseases, drug usage, history of prolonged standing and travel, smoking habit, number of pregnancies, history of varicose veins in the family, dermatological diagnosis/findings, and venous Doppler ultrasonography reports were examined retrospectively. RESULTS: 56% of patients were women. Mean age was 56.69 ± 13.6 years. Overall, 82.7% of total patients had at least one skin finding. The most frequent skin findings except varicose veins were insufficiency dermatitis accounted for 32.7% of patients, telangiectasia, and pigmentation which were comprised 25.3%, 19.3% of the total number of patients respectively. In addition to this, 48.7% of patients had itching problems and 32.7% had pain. Moreover, 46% of patients presented superficial vein insufficiency, while 8.7% had deep vein insufficiency. For 47.3% of patients, vein diameter dilation was observed and 11.3% suffered from perforating vein insufficiency. In terms of Clinical-Etiologic-Anatomic-Pathophysiologic (CEAP) classification, scores of 52% of the patients were C3 and lower, while scores of 48% of total patients were C4a and higher. CONCLUSIONS: Early diagnosis and treatment of chronic venous insufficiency could prevent further chronic processes such as venous ulceration which is an advanced CVI finding. Thus, assessing the early skin findings might be important to identify the underlying venous insufficiency disease.

Multiple cutaneous telangiectasias after the use of trastuzumab: a case report

We aim to report a particular case of cutaneous telangiectasias on the arms after immunotherapy with trastuzumab plus paclitaxel to treat breast cancer. New oncology therapies reflect a major advance in cancer treatment. They greatly increase survival; however, they still cause certain adverse cutaneous events that should be taken into account for their proper management.

Therapeutic Opportunities for Intestinal Angioectasia- Targeting PPARγ and Oxidative Stress.

Recurrent and acute bleeding from intestinal tract angioectasia (AEC) presents a major challenge for clinical intervention. Current treatments are empiric, with frequent poor clinical outcomes. Improvements in understanding the pathophysiology of these lesions will help guide treatment. Using data from the US Food and Drug Administration (FDA)'s Adverse Event Reporting System (FAERS), we analyzed 12 million patient reports to identify drugs inversely correlated with gastrointestinal bleeding and potentially limiting AEC severity. FAERS analysis revealed that drugs used in patients with diabetes and those targeting PPARγ-related mechanisms were associated with decreased AEC phenotypes (P < 0.0001). Electronic health records (EHRs) at University of Cincinnati Hospital were analyzed to validate FAERS analysis. EHR data showed a 5.6% decrease in risk of AEC and associated phenotypes in patients on PPARγ agonists. Murine knockout models of AEC phenotypes were used to construct a gene-regulatory network of candidate drug targets and pathways, which revealed that wound healing, vasculature development and regulation of oxidative stress were impacted in AEC pathophysiology. Human colonic tissue was examined for expression differences across key pathway proteins, PPARγ, HIF1α, VEGF, and TGFß1. In vitro analysis of human AEC tissues showed lower expression of PPARγ and TGFß1 compared with controls (0.55 ± 0.07 and 0.49 ± 0.05). National Center for Biotechnology Information (NCBI) Gene Expression Omnibus (GEO) RNA-Seq data was analyzed to substantiate human tissue findings. This integrative discovery approach showing altered expression of key genes involved in oxidative stress and injury repair mechanisms presents novel insight into AEC etiology, which will improve targeted mechanistic studies and more optimal medical therapy for AEC.

Weekly radiotherapy in elderly breast cancer patients: a comparison between two hypofractionation schedules.

PURPOSE: Weekly irradiation in breast cancer in elderly patients is a treatment option, whose tolerance may be influenced by the fractionation used. The objective of this study is to compare the tolerance and long-term side effects of two different fractionations. MATERIALS AND METHODS: 47 elderly patients were recruited after conservative or radical treatment that also received irradiation with a dose per fraction of 6.25 Gy or 5 Gy for one session per week, 6 sessions in total. The long-term tolerance results are compared by assessing toxicity using CTCAE version 5.0 scales for dermatitis, telangectasia, fibrosis and pain of the irradiated breast. In addition, objective parameters of skin status (erythema, hyperpigmentation, elasticity and hydration) by a multi-probe MultiSkin Test-Center system were obtained and compared between groups. RESULTS: After an average follow-up of 5 years, all patients were free of disease and with complete local control. A total of 20 patients with 6.25 Gy fractionation and 27 patients with 5 Gy fractionation have been included. Patients treated with lower fractionation had a lower incidence of dermatitis, telangectasia, fibrosis, or local pain. The decrease in elasticity measured by the multi-probe system was smaller with the fractionation of 5 Gy. No differences were observed in the other objective parameters. CONCLUSION: Weekly irradiation with 5 Gy fractionation is better tolerated than with higher fractionation.

A reliable skin toxicity predictor in permanent breast seed implant brachytherapy.

PURPOSE: To establish skin dose-outcome relationships using a reliable metric in permanent breast seed implant (PBSI). METHODS: Sixty-seven consecutive patients who underwent PBSI at our institution were included. Skin doses were calculated using two skin dose indices: maximum point dose to the skin surface, Dmax, and D0.2cc for a 2-mm internal skin rind (a surrogate to the dose to 1 cm2 area of skin) from CT-based postoperative treatment plans. Toxicity data were extracted from patients' charts and photographs. The associations between skin dose and skin toxicity were investigated using the analysis of variance, and the predictive performance of skin dose measures was evaluated using receiver operating characteristic curves. RESULTS: For acute reactions, 49.3% of patients had Grade 1, 4.5% Grade 2, and 1.5% Grade 3 toxicity. For telangiectasia at 3 years, very minor and minimally apparent telangiectasia was observed in 25% of patients. Moderate but asymptomatic telangiectasia was observed in 9.1% of cases. Both metrics were significantly associated with the occurrence of acute toxicity and telangiectasia at 3 years (p < 0.01). The predictive values for Dmax and D0.2cc were 0.779 and 0.763, respectively, (p < 0.0001) for acute skin toxicity and 0.786 and 0.810 for telangiectasia (p < 0.0002). Extreme dose outliers (up to 878 Gy) and a high variability were observed for Dmax but not for D0.2cc, illustrating the superior reliability of D0.2cc. CONCLUSION: D0.2cc, as an alternate skin dose measure to Dmax, is a robust metric for measuring skin dose that is simple to calculate, yet is clinically relevant and not prone to inaccuracies inherent to point dose measurement.

Pulmonary Arteriovenous Malformations in Non-hereditary Hemorrhagic Telangiectasia Patients: An 18-Year Retrospective Study.

PURPOSE: Pulmonary arteriovenous malformations (PAVMs) are most commonly associated with hereditary hemorrhagic telangiectasia (HHT). Patients with PAVMs can present with serious complications including stroke, transient ischemic attack (TIA), and brain abscess. PAVMs are rare in non-HHT patients and little is known about this patient population. The aim of this retrospective study is to better understand clinical presentation and outcomes of PAVMs occurring exclusively in non-HHT patients. METHODS: Non-HHT patients with PAVMs at the Mayo Clinic-Rochester between 01/01/2000 and 12/31/2018 were reviewed. Patients with Curacao score > 1 were excluded. Demographics, imaging characteristics, neurological complications, and follow-up imaging were analyzed. RESULTS: Seventy-seven patients with PAVMs were identified. The mean age at diagnosis was 48.2 ± 18.3 years with female preponderance (59.7%). The majority of PAVMs had lower lobe predominance (66.7%) and were simple and single in 75.3% and 89.6% of cases, respectively. Most patients were asymptomatic (46.8%) with dyspnea being the most common symptom (28.6%). Neurologic complications occurred in 19.5% of patients. The majority of PAVMs were idiopathic (61%). Thirty patients (39%) had one or more possible risk factors including previous thoracic surgery (23.4%), congenital heart disease (19.5%), and chest trauma (10.4%). Embolization was performed in 37 (48.1%) patients and only 4 (5.2%) underwent surgical resection. CONCLUSIONS: Non-HHT PAVMs occur more commonly in females, are most commonly simple and single, and have lower lobe predominance and a high rate of neurologic complications. Potential predisposing risk factors were identified in about 40% of the cases. Clinicians should be aware of the risk of PAVM development in patients with history of chest trauma, congenital heart disease, lung infection/abscess, and thoracic surgery.

Twenty-Year Incidence of Macular Telangiectasia Type 2 and Associated Systemic Comorbidities in Olmsted County, Minnesota.

BACKGROUND AND OBJECTIVE: To identify the incidence and associated systemic and ocular risk factors of macular telangiectasia (MacTel) type 2 using a population-based study. PATIENTS AND METHODS: In this retrospective cohort study, patients with MacTel type 2 were identified using the Rochester Epidemiology Project. An age- and sex-matched 4:1 cohort of healthy control patients was created to identify systemic medical comorbidities, medications, and ophthalmic risk factors with MacTel type 2. RESULTS: Over a 20-year time period, 18 patients with MacTel type 2 were identified. The overall incidence was 0.0007% per year. Adjusting for the age and sex of the Caucasian population in the 2010 U.S. census, the overall incidence was 0.0008% (95% CI, 0.4-1.2) per year. There were significantly more MacTel type 2 patients with type 2 diabetes (P = .007), hyperlipidemia (P = .03), and hypertriglyceridemia (P = .004). CONCLUSION: The incidence of MacTel type 2 in Olmsted County, Minnesota, is 0.7 per 100,000 persons per year. These patients are more likely to have type 2 diabetes and high cholesterol. The use of aspirin and nonsteroidal anti-inflammatory drugs may be protective factors. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:S35-S42.].