Multiple Telangiectasias Research Articles

Клинический случай повторных инфарктов головного мозга у пациента молодого возраста с болезнью Рандю-Ослера-Вебера

Rendu-Osler-Weber disease is a rare inherited disease of the vasculature, characterized by the development of multiple telangiectasias of the skin and mucous membranes, as well as hemorrhagic syndrome of various localization. We present a case report of recurrent acute ischemic strokes in a young patient with Rendu-Osler-Weber disease. In the first part of the article, literature data on the incidence, etiology, pathogenesis, features of clinical manifestations of hereditary hemorrhagic telangiectasia, modern methods of diagnosis and treatment are presented. In the second part of the article, a rare case of recurrent acute ischemic strokes in a young patient with Rendu-Osler-Weber disease, caused by a paradoxical embolism due to pulmonary arteriovenous malformation was demonstrated. The chest CT detected a pulmonary arteriovenous malformation. The data of medical, including anamnesis, a description of the objective and neurological status, the results of laboratory and instrumental methods of examination are presented. The patient was recommended angiopulmonography, during which the pulmonary arteriovenous malformation was successfully embolized. This case indicates the need for targeted examination and monitoring of patients with hereditary hemorrhagic telangiectasia. For the purpose of early detection of vascular malformations in patients with Rendu-Osler-Weber disease and the timely administration of therapy to prevent possible serious cerebrovascular complications, we recommend performing the chest CT.

Síndrome de Rendu Osler Weber en una adolescente en Colombia : reporte de un caso de autopsia.

La telangiectasia hemorrágica hereditaria es una enfermedad genética rara, perteneciente al grupo de púrpuras angiopáticas de tipo congénito, caracterizada por lesiones vasculares, encontrando frecuentemente telangiectasias en piel y mucosa del tracto gastrointestinal, fístulas arteriovenosas pulmonares y malformaciones vasculares en sistema nervioso central. Su manifestación clínica más frecuente son las hemorragias del tracto respiratorio superior. Este es el caso de una adolescente de 13 años con hallazgos de hepatopatía crónica, esplenomegalia difusa, pancitopenia, fístulas arteriovenosas pulmonares, deterioro neurológico progresivo secundario a hemorragia subaracnoidea con posterior defunción. Se realizó autopsia médicocientífica que reveló múltiples telangiectasias en mucosas, cirrosis de Osler, malformaciones arteriovenosas en polígono encefálico, hemorragia intraventricular con extensión subaracnoidea y bronconeumonía bibasal con pleuritis secundaria.

Intensity-Modulated Radiation Therapy with Stereotactic Body Radiation Therapy Boost for Unfavorable Prostate Cancer: A Report on 3-Year Toxicity.

Recent data suggest that intensity-modulated radiation therapy (IMRT) plus brachytherapy boost for unfavorable prostate cancer provides improved biochemical relapse-free survival over IMRT alone. Stereotactic body radiation therapy (SBRT) may be a less invasive alternative to brachytherapy boost. Here, we report the 3-year gastrointestinal (GI) and genitourinary (GU) toxicities of IMRT plus SBRT boost. Between March 2008 and September 2012, patients with prostate cancer were treated with robotic SBRT (19.5 Gy in three fractions) followed by fiducial-guided IMRT (45-50.4 Gy) on an institutional protocol. Toxicity was prospectively graded using the common terminology criteria for adverse events version 4.0 (CTCAEv.4) at the start of and at 1- to 6-month intervals after therapy. Rectal telangiectasias were graded using the Vienna Rectoscopy Score (VRS). At a median follow-up of 4.2 years (2.4-7.5), 108 patients (4 low-, 45 intermediate-, and 59 high-risk) with a median age of 74 years (55-92) were treated with SBRT plus IMRT, with 8% on anticoagulation and an additional 48% on antiplatelet therapy at the start of therapy. The cumulative incidence of late ≥grade 2 GI toxicity was 12%. Of these, 7% were due to late rectal bleeding, with six patients requiring up to two coagulation procedures. One patient with rectal telangiectasias was treated with hyperbaric oxygen (grade 3 toxicity). No rectal fistulas or stenoses were observed. Ten patients had multiple non-confluent telangiectasias (VRS grade 2), and three patients had multiple confluent telangiectasias (VRS grade 3). The cumulative incidence of late grade 3 GU toxicity was 6%. Most late toxicities were due to hematuria requiring bladder fulguration. There were no late ≥grade 4 GU toxicities. Rates of clinically significant GI and GU toxicities are modest following IMRT plus SBRT boost. Future studies should compare cancer control, quality of life, and toxicity with other treatment modalities for patients with high-risk prostate cancer.

Hereditary hemorrhagic telangiectasia associated with inherited thrombophilia

Introduction. Hereditary hemorrhagic telangiectasia and inherited thrombophilia are genetic disorders with quite opposite clinical manifestation. The main characteristic for hereditary hemorrhagic telangiectasia is recurrent bleeding, while the main characteristic for hereditary thrombophilia is thrombosis. The association between hereditary hemorrhagic telangiectasia and inherited thrombophilia in the same patient is rare. Case report. We presented a 32-year-old female with recurrent gastrointestinal hemorrhage and epistaxes, during a 9-year period. Hereditary hemorrhagic telangiectasia was established according to ?Cura?ao? criteria. Three of four criteria have been present: spontaneous recurrent epistaxis, multiple telangiectasias (nose) and visceral lesions (gastric angiodysplasias, jejunal telangiectasias, arterio- venous jejunal fistula). Pulmonary thromboembolism was the first manifestation of thrombophilia; the diagnosis was confirmed by genetic testing. Therapy of hemorrhage with tranexamic acid (anti-fibrinolytic agent; its use increases risk of thrombosis) was unsuccessful. Remission was achieved by thalidomide. The initial therapy for pulmonary thromboembolism included aspirin (that have an increased risk of bleeding), but aspirin had to be discontinued because of massive hematemesis. Unfortunately, a year later, anticoagulant therapy combined with the proton pump inhibitors, were introduced, because of a new thrombosis. One month after, the patient was still on this therapy, without new episodes of bleeding and thromboembolic events. Conclusion. Hereditary hemorrhagic telangiectasia and inherited thrombophilia could be unrecognized for years, partly due to the lower degree of clinical suspicion. Early diagnosis and the appropriate choice of therapy are essential for reducing serious consequences and to improve quality of life.

Recurrent Nasal Epistaxis, Osler-Weber-Rendu Syndrome

Clinical Image: A 60 y/o Caucasian female presents to the emergency room with epistaxis for 45 minutes. She also had 1 episode of hematemesis. She has been having recurrent epistaxis 1-2 episodes per week for last 2 years for which she was prescribed nasal ointment. She had history of hemoptysis 4 years ago, secondary to pulmonary AVMs which required coiling. (Figure 1A). No history of bleeding disorders in family. Currently she is not using aspirin or any other anticoagulants. On physical examination, multiple telangiectasia’s were noted on the tongue (Figure 1B) and abdomen (Figure 1C). During the hospitalization, patient underwent EGD which revealed Antral and Duodenal AVMs treated with thermal therapy and clipping. She fulfilled the 3 out of 4 Curacao criteria for Osler-Weber-Rendu syndrome. Genetic testing revealed she was positive for ENG (Endoglin) mutation known as hereditary hemorrhagic telangiectasia type 1 [HHT1].

ステロイド注腸が著効した放射線性腸炎の1例

A 86-year-old woman was admitted to our hospital with hematochezia. Colonoscopy was performed, and showed multiple telangiectasia and congestive bleeding on sigmoid colon. She has a medical history of uteri cancer and treated with radiation therapy. Thus, she was diagnosed radiation sigmoiditis. Argon plasma coagulation (APC) was performed, but because of its wide range of lesion, sufficient therapeutic effect could not obtained. The steroid suppository and enema are commonly used to treat proctitis and sigmoiditis, and which is considered to be effective to improve edema and inflammation of intestinal tract. Because of it, we started the steroid enema. After 10 days of treatment, colonoscopy was performed, and it shows the mucosal healing of sigmoid colon. This case suggests that combination of APC and the steroid enema are useful to the treatment of chronic hemorrhagic radiation sigmoiditis.

Long-Term Endoscopic Follow-Up of Patients with Chronic Radiation Proctopathy after Brachytherapy for Prostate Cancer.

Background. Chronic radiation proctopathy (CRP) is late toxicity and associated with morbidity. Aim. To investigate the predictors of prognosis in patients with CRP after brachytherapy (BT). Methods. One hundred four patients with prostate cancer were treated with BT or BT followed by external-beam radiotherapy (BT + EBRT). We retrospectively investigated the 5-year incidence of rectal bleeding and endoscopic findings of CRP using the Vienna Rectoscopy Score (VRS). Twenty patients with VRS ≥ 1 were divided into the improved VRS group without treatment, unchanged VRS group, and treated group. The parameters associated with alteration of VRS were analyzed. Results. The incidence of rectal bleeding was 24%. The risk of rectal bleeding was higher in patients treated with BT + EBRT compared to those treated with BT (p < 0.0001). The incidence of superficial microulceration was higher in the improved VRS group than in the unchanged VRS group (p < 0.05). The incidence of multiple confluent telangiectasia or superficial ulcers > 1 cm2 was higher in the treated group than in both the improved and unchanged VRS groups (p < 0.05). Conclusions. Patients treated with BT + EBRT have a high risk of CRP. Endoscopic findings were useful for prognostic prediction of CRP.

Reticulate Pigmentation Associated with Scarring Alopecia in an Elderly Woman: An Unusual Manifestation of Lichen Planus Pigmentosus.

A 70-year-old woman presented with generalized reticulate pigmentation, scarring alopecia, and few discrete, violaceous plaques over the trunk and forearm. Dermoscopic evaluation of the reticulate plaque showed reticulate hyperpigmentation with multiple telangiectasias, and skin biopsy showed lichenoid interface dermatitis with marked pigment incontinence. Thus, a final diagnosis of poikiloderma due to lichen planus pigmentosus was considered.

Dermoscopic Follow-Up of the Skin towards Acute Graft-versus-Host-Disease in Patients after Allogeneic Hematopoietic Stem Cell Transplantation.

Background. Acute graft-versus-host disease (aGVHD) involving skin is one of the most frequent complications of allogeneic hematopoietic stem cell transplantation (alloHSCT), usually diagnosed based on clinical manifestations. So far, skin biopsy with histopathological evaluation is the only method to confirm the diagnosis. Objective. In this prospective study we monitored alloHSCT recipients by dermoscopy in order to assess its utility as an alternative noninvasive tool to early diagnose acute GVHD. Methods. Thirteen consecutive patients who received alloHSCT were examined clinically and dermoscopically towards aGVHD [days 28 (±7), 56 (±7), and 100 (±7)], as well as in each patient who developed cutaneous aGVHD diagnosed according to clinical criteria (Glucksberg scale). Results. Six patients (46%) developed symptoms of cutaneous acute GVHD (grade 1, n = 3; grade 2, n = 3). Dermoscopic evaluation revealed pinkish or reddish background and well-visible, multiple thin telangiectasias. Conclusion. To our knowledge, this is the first report on the use of dermoscopy to evaluate skin involvement in the course of acute GVHD suggesting its role as a diagnostic tool in follow-up of GVHD, which can be also used before clinical symptoms occur.

Telangiectasia macularis multiplex acquisita accompanied by hepatitis B infection

We describe two rarely documented cases of telangiectasia macularis multiplex acquisita (TMMA) with a history of hepatitis B infection. Both patients presented with multiple erythematous macules and telangiectasia on bilateral upper arms and the upper part of the trunk. Patient 1 also had spider naevi on the upper part of the chest and palmar erythema; thus we inferred that TMMA, like spider naevi and palmar erythema, might belong to the spectrum of vascular changes of liver diseases.

Hereditary haemorrhagic telangiectasia presented with multiple brain abscesses and renal abscess in a Chinese patient: A case report

Hereditary haemorrhagic telangiectasia (HHT), or Osler–Weber–Rendu syndrome, is an autosomal dominant condition characterized by recurrent epistaxis, multiple telangiectasia and visceral vascular malformations. Brain abscess is a common presentation secondary to pulmonary arteriovenous malformation (AVM) in HHT patients. The prevalence of HHT in the Chinese population is not known, and is not commonly report. Here, we report on a Chinese patient who suffered from HHT and presented with multiple brain abscesses and a renal abscess. Upon further investigation of the patient's medical history and a physical examination, it was found that he had recurrent epistaxis and telangiectasia over his tongue, as well as fingers. Subsequent examination found pulmonary and hepatic AVM. He had a fair recovery after treatment of brain abscesses and pulmonary AVM. We believe HHT is underreported in the Chinese population. Simple history taking and physical examination in patients with a brain abscess can aid diagnosis and prevent complications with prophylactic treatment.

Aortic Dilatation Associated With a De Novo Mutation in the SOX18 Gene: Expanding the Clinical Spectrum of Hypotrichosis-Lymphedema-Telangiectasia Syndrome

BackgroundWe report a 13-year-old female patient followed since birth for multiple rare congenital defects, including hypotrichosis, telangiectasia, and severe dilatation of the ascending aorta. MethodsComprehensive phenotype assessment throughout childhood included repeated echocardiographic measurements, evaluation of renal function, and immunohistochemical analysis of skin biopsy samples. Whole-exome sequencing was performed for the patient and both unaffected parents. ResultsWe identified a novel de novo mutation in the transcription factor SOX18 (c.481C>T:p.Gln161*) in the patient, which was absent in all unaffected family members. Echocardiography revealed early onset and progressive dilatation of the ascending aorta. Skin biopsy results confirmed the defects of the blood vasculature in the presence of intact lymphatic vessels. Assessment of renal function did not show any signs of renal problems or renal failure in the patient. ConclusionsThe genetic finding of a pathogenic SOX18 mutation enabled the diagnosis of the rare hypotrichosis-lymphedema-telangiectasia syndrome in our patient. The identification of a novel stop gain mutation in the SOX18 gene in association with dilatation of the aorta highlights the importance of this gene during the development of the circulatory system. Our study highlights the importance of whole-exome sequencing in the rapid identification of genes and gene mutations involved in rare conditions and thus expanding the knowledge and spectrum of clinical manifestations associated with them.

Anti-angiogenic therapeutic strategies in hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant vascular dysplastic disorder, characterized by recurrent nosebleeds (epistaxis), multiple telangiectases and arteriovenous malformations (AVMs) in major organs. Mutations in Endoglin (ENG or CD105) and Activin receptor-like kinase 1 (ACVRL1 or ALK1) genes of the TGF-β superfamily receptors are responsible for HHT1 and HHT2 respectively and account for the majority of HHT cases. Haploinsufficiency in ENG and ALK1 is recognized at the underlying cause of HHT. However, the mechanisms responsible for the predisposition to and generation of AVMs, the hallmark of this disease, are poorly understood. Recent data suggest that dysregulated angiogenesis contributes to the pathogenesis of HHT and that the vascular endothelial growth factor, VEGF, may be implicated in this disease, by modulating the angiogenic–angiostatic balance in the affected tissues. Hence, anti-angiogenic therapies that target the abnormal vessels and restore the angiogenic–angiostatic balance are candidates for treatment of HHT. Here we review the experimental evidence for dysregulated angiogenesis in HHT, the anti-angiogenic therapeutic strategies used in animal models and some patients with HHT and the potential benefit of the anti-angiogenic treatment for ameliorating this severe, progressive vascular disease.

A rare case of pulmonary arterio-venous malformation with recurrent anemia: Hereditary hemorrhagic telangiectasia.

Arteriovenous malformation (AVM) is a rare vascular anomaly of the lung, which manifests predominantly as dyspnea (due to right to left shunting) and paradoxical embolism. Hereditary Hemorrhagic Telangiectasia (HHT) being a rare genetic disorder is one of the most common causes of pulmonary arteriovenous malformation (PAVM). Here we report an interesting case of recurrent anemia in an elderly female, who was subsequently found to have multiple cutaneous and mucosal telangiectasias and a large pulmonary AVM.

Hypotrichosis associated with capillary malformation-arteriovenous malformation syndrome.

Capillary malformation-arteriovenous malformation (CM-AVM) syndrome is associated with multifocal small CMs and a high risk for high-flow lesions. It is an autosomal dominant disorder, caused by RASA1 gene mutations. Recently, two novel clinical features have been identified: numerous small pale halos with central punctate red spots, and naevus anemicus. To identify the prevalence of the new clinical manifestations in our patients with CM-AVM. The secondary objective was to investigate the presence of other skin lesions. We retrospectively searched the picture database of our department for cases with a clinical diagnosis of CM-AVM, based on the identification of multiple cutaneous CMs and a negative history of epistaxis. We prospectively conducted a clinical and dermoscopic skin examination in all of these patients. Seven patients with multiple CMs were found, and only in one case was a cutaneous AVM present. Five patients had red punctate spots surrounded by pale halos on the upper limbs. Two adult patients also showed multiple telangiectasias on the neck and upper trunk. Naevus anemicus was not detected in any patient. A partial or total absence of vellous hair on the surface of CMs was observed in all patients. Red punctate spots with pale halos or small telangiectasias are frequent findings in CM-AVM syndrome. Hypotrichosis on the CMs suggests that RASA1 gene mutations could be involved in the hair follicle proliferation and cell cycle.

A Unique Case Presentation of Symptomatic Gastric Telangiectasia in Isolated Granulomatous Gastritis

Introduction: Literature has associated granulomatous gastritis with gastric ulcers but not with arteriovenous malformation, leading to transfusion dependent anemia. Case Report: A 32-year-old male patient with chronic blood transfusion and IV iron dependent anemia from chronic gastrointestinal blood loss for 7 years despite repeated cauterization of angiodysplasia in his stomach. He has intermittent melena, one episode of scant hematemesis in past, 40 lbs weight loss, no other GI symptoms, no NSAID/anticoagulants, no coagulopathy; no symptoms to suggest systemic vasculitis, sarcoidosis or inflammatory bowel disease. No contributing past medical, surgical or family history. He denies use of alcohol or recreational drugs; smokes half a pack of cigarettes/day. Uses carafate and omeprazole twice a day. BMI 26.5, unremarkable vitals and physical exam. He has had several endoscopies. Cumulative findings on EGD: several clean base superficial and irregular shaped antral ulcer, multiple spider telangiectasia on all mucosal surfaces of stomach, central portion bled with touch. Stomach biopsy: moderate active gastritis with noncaseating epithelioid granulomas, no microorganisms. Special stains: H. pylori, fungus and AFB were negative; Fungal and AFB cultures of biopsies are negative (3 months). Esophagus and small bowel biopsies were normal. Twice colonoscopy: normal, including terminal ileum. Capsule endoscopy: multiple AVM in stomach, antral ulcer, old hematin in distal small bowel, otherwise normal small bowel. Serology: negative for HIV, normal haptoglobin and ristocetin cofactor; W/u for Von Willebrand syndrome, factor 8 activity 225%; VWF ag normal. Doppler US: no portal vein thrombosis; ESR: 2. Infectious causes: negative for syphilis and schistosomiasis, PCR for Whipple’s bacillus negative, H. pylori IgG Ab positive; Histoplasma Ab negative (no eosinophilia and no eosinophillic granulomas). Normal serum protein electrophoresis. Vasculitis: negative autoantibodies to proteinase 3, myeloperoxidase, ANA. Sarcoidosis: CT chest/abd/pelvis: no lung infiltrate or signs of sarcoidosis; few tiny visible retroperitoneal nodes; normal liver/spleen, ACE level is normal. Assessment: isolated granulomatous gastritis, without recognizable infection, systemic sarcoidosis, or small bowel/colon Crohn’s disease. Plan is aimed to eradicate H pylori, treat with steroids, similar to treatment of Crohn’s disease; if repeat endoscopy shows improvement then slow taper of steroids, if has recurrence then consider azathioprine. Conclusion: This case report will contribute to the limited literature on isolated granulomatous gastritis, with a unique association of symptomatic AVM’s.

Clinical Practice Recurrent Severe Obscure Gastro Intestinal- Bleeding in a 20 Year Old Man

Morbus Osler-Weber-Rendu syndrome also known as Hereditary hemorrhagic telangiectasia (HHT) and Meckel's diverticulum is a rare combination disorder. Our case presented with the recurrent obscure gastrointestinal (GI) bleeding for several years. He came with a massive active lower gastrointestinal bleeding. Ultimatively, he underwent an exploratory laparotomy along with intraoperative colonoscopy. A Meckel's diverticulum in combination with multiple erosions was found as a probable cause of the massive gastrointestinal bleeding. An ileo-caeacal resection had been performed and by the pathologist multiple telangiectasias in the resected ileum were established. Blood was sent for genetics and was negative for ENG, ALK-1, and SMAD-4 genes. The patient was discharged after 10 days from time of admission and is under regular follow up without any further bleeding. In this case, despite sophisticated techniques for investigations the cause of the GI-bleeding with several esophagogastroduodenoscopies and colonoscopies, mesenteric angiography and finally an oral double balloon enteroscopy was misdiagnosed till the intra operative endoscopy showed a middle GI-bleeding. The management for obscure GI-bleeding is discussed for countries with lower medical facilities like Nepal in our case with Morbus Osler-Weber-Rendu syndrome.

La maladie de Rendu-Osler-Weber : à propos d’une nouvelle observation pédiatrique

Hereditary hemorrhagic telangiectasia, or Rendu-Osler-Weber syndrome, is an autosomal dominant multiorgan disorder. This multisystemic vascular dysplasia is determined by a mutation of one of two main genes, endoglin (ENG) or HHT1, or ACVRL1 or HHT2. These mutations induce vascular disorders that cause recurrent epistaxis and eventually multiple telangiectasia and arteriovenous visceral malformations. We report the case of a 7-year-old girl who developed severe hypoxemia due to multiple pulmonary arteriovenous malformations.

A Case of Generalized Essential Telangiectasia with Early Onset

Observations: A 26-year-old woman attended to our outpatient clinic with widespread and progressively enlarging redness, without any subjective complaint and history of hemorrhagic episodes. The lesions had been present since her childhood. Dermatological examination showed patches which consisted of multiple fine telangiectasias on the face, anterior neck, trunk, upper and lower extremities and bilateral palms. She was diagnosed as generalized essential telangiectasia (GET) with medical history, clinical apperance of the lesion and histopathological findings. GET is an uncommon disorder characterized with generalized telangiectasia and it occurs in ages between late thirties to late fourties. We report a case of GET with early onset.

A young military pilot presents with a periocular Basal Cell Carcinoma: A case report

Basal Cell Carcinoma (BCC) is the most common form of skin malignancy in the UK with 75, 000 new cases per year. It commonly presents as a non-healing lesion in the H zone of the face. The significant risk factors for this condition include UV radiation exposure and a history of sunburn. The gold standard treatment for BCC is Mohs Micrographic Surgery as well a variety of traditional surgical and non-surgical options. A 32 year old white male military helicopter pilot presented with a pea sized lesion which appeared highly vascularised with multiple telangiectasia on the surface. The main risk factors were regular foreign travel to regions of high UV radiation and previous episodes of sunburn. BCC is the commonest form of eye lid malignancy and any form of non-healing lesion on the periocular area should be investigated as a possible neoplasm. The main risk factors are travel to areas of high UV radiation and exposure to UV radiation as a child. There is also a possible risk factor of occupational exposure to ionising radiation from cosmic sources although there is limited research to support this. This is an interesting case of an unusual first presentation of a BCC in a male under 40 years of age and demonstrates the important risk factors in a military population for developing a non-melanoma skin cancer.