Not Your Typical Nosebleed: A Case Report and Personal Account of a Patient With Osler-Weber-Rendu Syndrome.

Introduction Osler-Weber-Rendu syndrome, or hereditary hemorrhagic telangiectasia, is a rare genetic disease that causes recurrent epistaxis and anemia. Numerous bleeding vascular malformations can be found throughout the body. Case presentation A 75-year-old woman presented to her hematologist with recurrent epistaxis, iron deficiency anemia, menorrhagia, and hypothyroidism. Her mother had similar nosebleeds, and physical examination revealed small vascular malformations on the conjunctiva, oropharynx, tongue, lip, and palate. Heavy epistaxis occurred several times per week. Multiple nasal and gastrointestinal endoscopic procedures were performed. She received over 100 iron infusions and multiple blood transfusions. Overall treatment involved integrated care with multiple medical specialties. Conclusion Hereditary hemorrhagic telangiectasia and other complex diseases are best treated with a multidisciplinary approach within an integrated health care setting.

Hereditary hemorrhagic telangiectasia with liver cirrhosis: a case report.

BACKGROUND: Hereditary hemorrhagic telangiectasia is an autosomal dominant hereditary hemorrhagic disease. Its main feature is an abnormal structure of the blood vessel wall. Cirrhosis of the liver is a common chronic progressive disease with one or more causes in which diffuse liver damage occurs after long-term or repeated injury. Liver cirrhosis can cause dilation of gastrointestinal capillaries. Many patients with hereditary hemorrhagic telangiectasia accompanied by gastrointestinal vascular malformations and liver cirrhosis may be diagnosed only with liver cirrhosis if the clinician does not pay attention to physical examination findings and family history. Moreover, general treatment measures, such as blood transfusion, iron supplementation, and application of hemostatic drugs, are less effective for bleeding in patients with hereditary hemorrhagic telangiectasia than in those with liver cirrhosis alone. CASE PRESENTATION: Here, we report the rare case of a 75-year-old Chinese man who was admitted to the hospital with repeated melena and epistaxis. He was diagnosed with unexplained liver cirrhosis, which was later confirmed as hereditary hemorrhagic telangiectasia. Subsequently, we implemented the treatment intervention of oral thalidomide combined with gastrointestinal argon plasma coagulation. A follow-up of more than 8 months showed that the treatment effect was excellent. CONCLUSIONS: If patients with liver cirrhosis and gastrointestinal vascular malformations also have a family history of epistaxis, special attention should be paid to targeted physical examination results, and the possibility of hereditary hemorrhagic telangiectasia should be considered. Moreover, for patients with hereditary hemorrhagic telangiectasia and both gastrointestinal bleeding caused by gastrointestinal capillaries and repeated epistaxis, when other general treatment measures are ineffective, thalidomide combined with gastrointestinal argon plasma coagulation may be an effective intervention.

Hereditary hemorrhagic telangiectasia (OslerWeberRendu syndrome) - Part II. Pharmacological therapy and international guidelines for the therapy 2020.

Hereditary hemorrhagic telangiectasia also known as Osler-Weber-Rendu syndrome, is an disorder that causes abnormal blood vessel formation with bleeding. Inhibition of angiogenesis amelioretes bleeding complication. Anti-angiogenic agents such as bevacizumab, aflibercept, thalidomid, lenadomid and other new anti-angiogenic thyrosinkinase inhibitors, as well as sirolimus and takrolimus have emerged as a promising systemic or local therapy in reducing bleeding complications but are not curative. Other pharmacological agents include iron supplementation, antifibrinolytics and hormonal treatment. This review concentrates on new anti-agioproliferative drugs with effect in HHT- discusses the new biology of HHT, management issues that face the practising hematologist, and considerations of future directions in HHT treatment.

Probiotics and infective endocarditis in patients with hereditary hemorrhagic telangiectasia: a clinical case and a review of the literature.

BACKGROUND: In the last decades, probiotics have been widely used as food supplements because of their putative beneficial health effects. They are generally considered safe but rare reports of serious infections caused by bacteria included in the definition of probiotics raise concerns on their potential pathogenic role in patients with particular predisposing factors. Patients with hereditary hemorrhagic telangiectasia (HHT) are exposed to infections because of telangiectasias and arteriovenous malformations (AVMs). We describe what is, to our knowledge, the first case of infective endocarditis (IE) caused by Lactobacillus rhamnosus in a patient with HHT. A systematic review of the relevant medical literature is presented. CASE PRESENTATION: A patient with HHT and an aortic bioprosthesis was admitted because of prolonged fever not responding to antibiotics. The patient had a history of repeated serious infections with hospitalizations and prolonged use of antibiotics, and used to assume large amounts of different commercial products containing probiotics. Weeks before the onset of symptoms the patient had been treated with nasal packings and with surgical closure of a nasal bleeding site because of recurrent epistaxis. A diagnosis of IE of the aortic bioprosthesis was made. All blood coltures were positive for L. rhamnosus. The patients responded to a cycle of 6 weeks of amoxicillin/clavulanate plus gentamicin. A systematic review of IE linked to consumption of probiotics, and of infective endocarditis in patients with HHT was conducted. 10 cases of IE linked to probiotics consumption and 6 cases of IE in patients with HHT were found. CONCLUSIONS: Consumption of probiotics can pose a risk of serious infections in patients with particular predisposing factors. Patients with HHT can be considered at risk because of their predisposition to infections. Prophylaxis with antibiotics before nasal packings in patients with HHT can be considered.

Influence of temporary nasal occlusion (tNO) on epistaxis frequency in patients with hereditary hemorrhagic telangiectasia (HHT).

The objective of the study was to evaluate the influence of temporary nasal occlusion (tNO) with hypoallergenic tape on the frequency and severity of epistaxis in patients with hereditary hemorrhagic telangiectasia (HHT). This prospective observational study included 20 HHT patients who were undergoing Nd:YAG laser therapy at regular intervals. Over a 3-month period, laser therapy was supplemented by tNO with hypoallergenic tape for 5 h/day on average. On a 0-10 numeric rating scale, the patients reported significantly greater satisfaction in epistaxis terms after tNO treatment, with mean scores of 5 before and 7 after 3-month tNO (p = 0.05). The Epistaxis Severity Score also fell significantly from a median of 3.59-2.43 after 3-month tNO compared with laser therapy alone (p = 0.01). The patients' hemoglobin levels remained stable during the study (median: 12.2 g/dL before tNO; median: 11.7 g/dL after tNO; p = 0.387). Overall, the present study confirms the positive influence of tNO on epistaxis in HHT patients and on subjective satisfaction. This simple and inexpensive strategy is therefore a helpful option, especially in addition to regular Nd:YAG laser therapy, and is recommended by the authors.

Immunological abnormalities associated with hereditary haemorrhagic telangiectasia.

OBJECTIVE: Hereditary haemorrhagic telangiectasia (HHT) is a genetic disorder related to mutations in one of the coreceptors to the transforming growth factor-ß superfamily (ALK1 or endoglin). Besides the obvious vascular symptoms (epistaxis and arteriovenous malformations), patients have an unexplained high risk of severe bacterial infections. The aim of the study was to assess the main immunological functions of patients with HHT using the standard biological tests for primary immunodeficiencies. DESIGN, SETTING AND SUBJECTS: A prospective single-centre study of 42 consecutive adult patients with an established diagnosis of HHT was conducted at the National French HHT Reference Center (Lyon). Lymphocyte subpopulations and proliferation capacity, immunoglobulin levels and neutrophil and monocyte phagocytosis, oxidative burst and chemotaxis were assessed. RESULTS: Innate immunity was not altered in patients with HHT. With regard to adaptive immunity, significant changes were seen in immunological parameters: primarily, a lymphopenia in patients with HHT compared with healthy control subjects affecting mean CD4 (642 cells µL(-1) vs. 832 cells µL(-1) , P < 0.001), CD8 (295 cells µL(-1) vs. 501 cells µL(-1) , P < 0.0001) and natural killer (NK) cells (169 cells µL(-1) vs. 221 cells µL(-1) , P < 0.01), associated with increased levels of immunoglobulins G and A. This lymphopenia mainly concerned naïve T cells. Proliferation capacities of lymphocytes were normal. Lymphopenic patients had a higher frequency of iron supplementation but no increase in infection rate. Lower levels of immunoglobulin M and a higher rate of pulmonary arteriovenous malformations were found amongst patients with a history of severe infection. CONCLUSIONS: Patients with HHT exhibit immunological abnormalities including T CD4, T CD8 and NK cell lymphopenia and increased levels of immunoglobulins G and A. The observed low level of immunoglobulin M requires further investigation to determine whether it is a specific risk factor for infection in HHT.

Efficacy of a topical sesame/rose geranium oil compound in patients with hereditary hemorrhagic telangiectasia associated epistaxis.

OBJECTIVES/HYPOTHESIS: Topical Sesame/Rose geranium oil compound is an effective therapy for hereditary hemorrhagic telangiectasia (HHT) associated epistaxis. STUDY DESIGN: Cohort Study. METHODS: Twenty patients with HHT confirmed by the Curaçao criteria were treated with a sesame/rose geranium oil topical compound between January 2010 and June 2011. A treatment evaluation survey was conducted at least 3 months after treatment initiation. Changes in epistaxis severity scores (ESS), patient satisfaction, and any adverse effects were assessed. RESULTS: A total of 20 patients completed the study. The average (SD) age was 54.4 (14.6), and 14 (70%) were female. The median time on rose geranium oil was 183 days (IQR: 114-311). At the conclusion of the study, 18 (90%) were still using rose geranium oil. The majority (75%) of patients subjectively felt improvement with the treatment. The improvement was felt to be gradual in 25% and immediate in 50% of patients. Mean (SD) overall satisfaction using a 10-point Likert scale was 7.8 (3.1), with 50% of the patients reporting a satisfaction rating of 10. Mean (SD) epistaxis severity score (ESS) prior to treatment was 5.3 (1.7). After treatment with sesame/rose geranium oil, mean (SD) ESS was found to be 3.5 (1.8). Treatment with sesame/rose geranium oil was associated with a statistically significant improvement in ESS by 1.81 (P <0.0001). There were no adverse side-effects from the treatment. CONCLUSION: A sesame/rose geranium oil compound can significantly reduce the epistaxis severity scores of patients with hereditary hemorrhagic telangiectasia-related epistaxis.

Bevacizumab in hereditary hemorrhagic telangiectasia-associated epistaxis: effectiveness of an injection protocol based on the vascular anatomy of the nose.

OBJECTIVE/HYPOTHESIS: To evaluate the effectiveness of a standardized intranasal bevacizumab injection in treating hereditary hemorrhagic telangiectasia (HHT)-associated epistaxis. STUDY DESIGN: Prospective pilot study. METHODS: A total dose of 100 mg bevacizumab (25 mg/mL Avastin) was injected submucosally, 50 mg on each side. A total of 0.5 mL was injected in the sphenopalatine area, upper part of bony septum, upper part of the later nasal wall, and the anterior part of nasal floor. No cauterizations or laser therapy were done during or after the procedure. The hemoglobin level and grades of epistaxis were recorded before and monthly after the procedure. The IFT grading system (intensity [I], frequency [F] of epistaxis, and the amount of blood transfusion [T]) and epistaxis severity score (ESS) for hereditary hemorrhagic telangiectasia system were used. Quality of life (QoL) was evaluated before and 4 weeks after the procedure using the Short Form-36 Health Survey questionnaire, Cantril's Self-Anchoring Ladder questionnaire, and Slotosch disease-specific QoL questionnaire. RESULTS: A significant improvement was found in IFT grading (P = .007), ESS grading (P = .001), and hemoglobin level (P = .01). The QoL differences were statistically not significant. CONCLUSIONS: The four-injection site technique of intranasal administration of bevacizumab is an effective treatment option in HHT-associated epistaxis, at least on the short-term effect. Long-term and comparative studies are needed to further evaluate the significance of this treatment modality.

Individualized management of hepatic diseases in hereditary hemorrhagic telangiectasia.

Liver involvement in patients with hereditary hemorrhagic telangiectasia (HHT) has not been fully characterized in China. The clinical manifestations, imaging studies, results of treatment in six patients and symptomatic liver involvement were analyzed. Patients included three women and three men with age from 35 to 62 years old. Two patients presented with shortness of breath, one patient with anemia and splenomegaly, and one with chronic gastrointestinal bleeding; the remaining two were asymptomatic. CT and CT angiography (CTA) showed arterioportal and arteriovenous shunting in liver. CTA showed at least one enlarged hepatic artery in all patients. One patient received ligation of the enlarged arteries with subsequent disappearance of symptoms at 56-month follow-up. The patient with gastrointestinal bleeding received interventional embolotherapy and resolved; interventional therapy to embolize the enlarged hepatic arteries was unsuccessful in another patient and the patient died of heart failure and liver dysfunction 38 months later. The patient with splenomegaly received a splenectomy and bandage of an enlarged hepatic artery. One of the two patients with no symptoms died of liver dysfunction 41 months after diagnosis. The other showed abnormal liver function and ascites, and traditional Chinese medicinal herb was used with no effect 21 months later. The symptoms disappeared after systemic medical treatment. Individualized and active therapy is advantageous and proper for patients with HHT.

The effect of bevacizumab (Avastin) treatment on epistaxis in hereditary hemorrhagic telangiectasia.

OBJECTIVES/HYPOTHESIS: Determine the effectiveness of treating epistaxis in hereditary hemorrhagic telangiectasia (HHT) with potassium titanyl phosphate (KTP) laser cautery combined with submucosal injection of 100 mg of bevacizumab. STUDY DESIGN: Retrospective pilot study. METHODS: Bevacizumab was injected throughout the nasal cavity following KTP laser treatment in 10 patients (bevacizumab/KTP group) and compared to nine patients previously treated with KTP laser alone (KTP group). Epistaxis frequency and severity, blood transfusion requirement, intravenous iron supplementation, emergency department visit frequency, and quality of life within 1 month and 1 year pre- and postsurgery were analyzed. Benefit was defined as less than three nosebleeds per week, with less than 10 minutes to stop each nosebleed, and no blood transfusions. The pre- and postsurgery data were analyzed within and between the two groups. RESULTS: The groups were comparable in age and gender. Significant benefit was found in frequency of epistaxis (P < .05), number of blood transfusions (P = .04), disability (P = .01), and effect on social life (P = .03) 1 month pre- and postsurgery in the bevacizumab/KTP group. Eighty percent of bevacizumab/KTP group patients reported benefit in comparison to 56% in the KTP group. CONCLUSIONS: KTP laser combined with bevacizumab in HHT epistaxis is superior to KTP laser treatment alone. It significantly decreases frequency and severity of nosebleeds and blood transfusion requirements, and significantly improves work ability and quality of life.

Treatment of epistaxis in hereditary hemorrhagic telangiectasia patients by argon plasma coagulation with local anesthesia.

BACKGROUND: Recurrent epistaxis is the most common manifestation of hereditary hemorrhagic telangiectasia (HHT). The aim of this study was to determine the role and efficacy of argon plasma coagulation (APC) in the management of epistaxis caused by HHT. METHODS: From 1997 to 2004, 43 patients with diagnosed HHT were treated for recurrent epistaxis with APC in our department. RESULTS: Thirty-six patients reported substantial reduction of bleeding after treatment. Of the 18 patients who previously needed blood transfusions, 13 reported substantial reduction of bleeding after treatment and no blood transfusions were necessary. CONCLUSION: APC allows a control of epistaxis in HHT patients and guarantees a long time free from blood transfusions. This treatment modality can be performed with local anesthesia, is not invasive, is well tolerated, is inexpensive, and can be used as a first step even in patients who need to undergo several blood transfusions for their epistaxis.

Clinical strategy in hereditary hemorrhagic telangiectasia.

BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is a recurrent bleeding tendency caused by vascular malformations and preferentially involving the mucous membrane of the nose. The rhinological management of epistaxis is a challenge in which the frequency of bleeding has to be reduced without damage to the nasal mucosa, despite the fact that therapy necessarily has to be repeated. METHODS: The clinical course in 30 patients with HHT was monitored prospectively. Nasal mucosal efflorescences underwent Nd:YAG laser therapy at individually defined intervals, and the effect on the frequency and duration of bleeding was documented, as were adverse effects. RESULTS: No serious adverse effects (e.g., septal defects or synechiae) were observed as a consequence of therapy. During the course of laser therapy and ongoing compliance with nasal mucosal care instructions, the frequency of bleeding fell from "several times daily" to "every 2 weeks." CONCLUSION: In conjunction with Nd:YAG laser therapy, ongoing and consistent care of the nasal mucosa is a proven and effective treatment regimen in HHT. As an integral element in an interdisciplinary strategy for diagnosis and therapy, this regimen yields satisfactory quality of life while avoiding local complications.

[Pulmonary hypertension in hereditary haemorrhagic teleangiectasia (Rendu-Osler-Weber disease). Progression over 10 years]. / Pulmonale Hypertonie bei hereditärer hämorrhagischer Teleangiektasie (Morbus Osler). Verlauf über 10 Jahre.

HISTORY: 10 years ago a now 49-year-old woman with Render-Osler-Weber disease showed unspecific symptoms of nausea, and general unwellness. Pulmonary manifestation of the disease was accompanied by pulmonary hypertension. INVESTIGATION: Teleangiectasia of the tongue and pharynx as well as of the mucosa of mouth and nose were observed. Fixed-splitting of the second heart sound with accentuated pulmonary component and a 2/6 systolic murmur over the tricuspid valve were heard. In addition, a murmur was heard dorsal over the right lung's lower lobe. Apart from minor oedema of both ankles, the physical status was not remarkable. Echocardiography showed dilatation of the right ventricle and a minor regurgitation of the tricuspid valve. The computed tomography showed dilatation of the pulmonary arteries as well as an arteriovenous malformation in the right lower lobe. Right-heart catheterisation revealed elevated pulmonary pressure. THERAPY AND FOLLOW-UP: Initial treatment with a calcium channel blocker proved insufficient and was changed to inhalative, and later to oral prostanoids. Under this treatment the cardiopulmonary state was stabilised, but episodes of epistaxis were increased. Two years after readjustment of the medication to a dual endothelin receptor antagonist, the cardiopulmonary state remains stable without significant haemorrhagic complications. CONCLUSION: Prostanoid treatment in patients with Render-Osler-Weber disease and additional pulmonary hypertension can lead to an increased risk of haemorrhagic complications. Treatment with newer medications, such as endothelin receptor antagonists, seems indicated as successfully illustrated in our case.

Topical estrogens combined with argon plasma coagulation in the management of epistaxis in hereditary hemorrhagic telangiectasia.

The aim of this study was to assess the value of topically applied estrogens in patients with hereditary hemorrhagic telangiectasia. Twenty-six patients with this disorder were treated with argon plasma coagulation and randomized into 2 groups: group A, which had postoperative application of estriol ointment (n = 14), and group B, which had postoperative application of dexpanthenol ointment (n = 12). Over a period of 12 months, the frequency and intensity of bleeding, the patient's satisfaction, and the success of the treatment were evaluated with a questionnaire. Before the operation, more than 90% of the patients in both groups complained of daily episodes of epistaxis. Twelve months after treatment, the frequency and intensity of bleeding had significantly decreased in group A as compared to group B. Of the patients in group A, 93% were satisfied with the treatment. Of the patients in group B, only 42% were satisfied with the treatment. In both groups, more than 90% of the patients were willing to undergo the same treatment again. The combined treatment approach with argon plasma coagulation and topical estriol enables us to significantly prolong the hemorrhage-free interval.

[Chronic, hemorrhage-induced iron deficiency anemia in Osler disease]. / Chronische, blutungsbedingte Eisenmangelanämie bei Morbus Osler.

We report the history of a 77-year-old man with Osler-Weber-Rendu disease (hereditary hemorrhagic telangiectasia) who suffered from recurrent epistaxis and chronic bleeding anemia for many years. Hereditary hemorrhagic telangiectasia is a rare congenital disease, that is characterized by telangiectases of the nasal and oral mucosa, the gastrointestinal tract and the skin. Arteriovenous malformations of the lung and the brain may be present. The genetic and pathologic features, the clinical manifestations and the differential diagnosis are shortly presented. The management is not validated by controlled studies and is mainly based on clinical experience. It involves supportive therapy with iron supplementation and erythrocyte transfusions, if needed, for chronic bleeding anemia, aminocaproic acid, tranexamic acid or oestrogen-progesterone therapy to prevent mucosal bleeding, cauterisation, photocoagulation, transcatheter embolotherapy or surgery to treat the vascular abnormalities.

[Stepwise diagnosis of intestinal hemorrhage]. / Stufendiagnostik der intestinalen Blutung.

Endoscopy is the method of choice in diagnosing gastrointestinal bleeding. In case of acute and severe bleeding a bleeding-source in the upper gastrointestinal tract has to be excluded with priority. The efficiency of endoscopy would be enhanced by endoscopic Doppler ultrasound. A diagnostic gap in the region of small bowel possibly will be closed by recently developed push-enteroscopy. Angiography and scintigraphy with labeled autologous erythrocytes are reserved to bleeding of still unknown source. Enteroclysis and double contrast barium enema are necessary only in very rare cases.

[Rendu-Osler-Weber syndrome presented paramedian thalamic and midbrain infarcts and primary medullary hemorrhage: a case report].

We reported a 41-year-old male with paramedian thalamic and midbrain infarcts due to cerebral embolism from bilateral pulmonary arterio-venous fistula and primary medullary hemorrhage. The patient had an episode of sudden onset consciousness disturbance with left Weber's syndrome (right hemiplegia and left oculomotor palsy) and vertical gaze palsy at age of 23. He noticed numbness in the left hand and the left half body under clavicular when he had got up in a morning at age 41. He had headache and left tinnitus on second and third days, and on the 3rd and 4th days, he experienced nausea. He had severe hiccup persisting from the 6th to the 13th days. The 23rd days he was admitted to our hospital. He showed dysesthesia and paresthesia in left half body under clavicular, dysesthesia in left hand and vertical gaze palsy and convergence disturbance. MRI performed on the 18th and 24th days, disclosed hyperdense mass in T1 and T2-weighted images in dorsal site of medulla, but the 70th days MRI showed no abnormal lesions. Therefore we diagnosed the high intensity mass as primary medullary hemorrhage. Cerebral angiography showed no abnormal vasculature. Many members of his family had history of sever nasal bleeding. He had skin hemangioma and mucosal hemangioma in esophagus, stomach, colon and rectum, and bilateral pulmonary arterio-venous fistula which had been operated at age 39. His mother also had skin hemangioma and pulmonary arterio-venous fistula. Therefore this family was diagnosed Rendu-Osler-Weber syndrome (hereditary hemorrhagic telangiectasia). MRI also disclosed multiple cerebral infarctions in bilateral thalamus, left cerebral peduncle and left cerebellar hemisphere.(ABSTRACT TRUNCATED AT 250 WORDS)