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.

Clinical Practice Guideline: Nosebleed (Epistaxis).

OBJECTIVE: Nosebleed, also known as epistaxis, is a common problem that occurs at some point in at least 60% of people in the United States. While the majority of nosebleeds are limited in severity and duration, about 6% of people who experience nosebleeds will seek medical attention. For the purposes of this guideline, we define the target patient with a nosebleed as a patient with bleeding from the nostril, nasal cavity, or nasopharynx that is sufficient to warrant medical advice or care. This includes bleeding that is severe, persistent, and/or recurrent, as well as bleeding that impacts a patient's quality of life. Interventions for nosebleeds range from self-treatment and home remedies to more intensive procedural interventions in medical offices, emergency departments, hospitals, and operating rooms. Epistaxis has been estimated to account for 0.5% of all emergency department visits and up to one-third of all otolaryngology-related emergency department encounters. Inpatient hospitalization for aggressive treatment of severe nosebleeds has been reported in 0.2% of patients with nosebleeds. PURPOSE: The primary purpose of this multidisciplinary guideline is to identify quality improvement opportunities in the management of nosebleeds and to create clear and actionable recommendations to implement these opportunities in clinical practice. Specific goals of this guideline are to promote best practices, reduce unjustified variations in care of patients with nosebleeds, improve health outcomes, and minimize the potential harms of nosebleeds or interventions to treat nosebleeds. The target patient for the guideline is any individual aged ≥3 years with a nosebleed or history of nosebleed who needs medical treatment or seeks medical advice. The target audience of this guideline is clinicians who evaluate and treat patients with nosebleed. This includes primary care providers such as family medicine physicians, internists, pediatricians, physician assistants, and nurse practitioners. It also includes specialists such as emergency medicine providers, otolaryngologists, interventional radiologists/neuroradiologists and neurointerventionalists, hematologists, and cardiologists. The setting for this guideline includes any site of evaluation and treatment for a patient with nosebleed, including ambulatory medical sites, the emergency department, the inpatient hospital, and even remote outpatient encounters with phone calls and telemedicine. Outcomes to be considered for patients with nosebleed include control of acute bleeding, prevention of recurrent episodes of nasal bleeding, complications of treatment modalities, and accuracy of diagnostic measures. This guideline addresses the diagnosis, treatment, and prevention of nosebleed. It focuses on nosebleeds that commonly present to clinicians via phone calls, office visits, and emergency room encounters. This guideline discusses first-line treatments such as nasal compression, application of vasoconstrictors, nasal packing, and nasal cautery. It also addresses more complex epistaxis management, which includes the use of endoscopic arterial ligation and interventional radiology procedures. Management options for 2 special groups of patients-patients with hereditary hemorrhagic telangiectasia syndrome and patients taking medications that inhibit coagulation and/or platelet function-are included in this guideline. This guideline is intended to focus on evidence-based quality improvement opportunities judged most important by the guideline development group. It is not intended to be a comprehensive, general guide for managing patients with nosebleed. In this context, the purpose is to define useful actions for clinicians, generalists, and specialists from a variety of disciplines to improve quality of care. Conversely, the statements in this guideline are not intended to limit or restrict care provided by clinicians based on their experience and assessment of individual patients. ACTION STATEMENTS: The guideline development group made recommendations for the following key action statements: (1) At the time of initial contact, the clinician should distinguish the nosebleed patient who requires prompt management from the patient who does not. (2) The clinician should treat active bleeding for patients in need of prompt management with firm sustained compression to the lower third of the nose, with or without the assistance of the patient or caregiver, for 5 minutes or longer. (3a) For patients in whom bleeding precludes identification of a bleeding site despite nasal compression, the clinician should treat ongoing active bleeding with nasal packing. (3b) The clinician should use resorbable packing for patients with a suspected bleeding disorder or for patients who are using anticoagulation or antiplatelet medications. (4) The clinician should educate the patient who undergoes nasal packing about the type of packing placed, timing of and plan for removal of packing (if not resorbable), postprocedure care, and any signs or symptoms that would warrant prompt reassessment. (5) The clinician should document factors that increase the frequency or severity of bleeding for any patient with a nosebleed, including personal or family history of bleeding disorders, use of anticoagulant or antiplatelet medications, or intranasal drug use. (6) The clinician should perform anterior rhinoscopy to identify a source of bleeding after removal of any blood clot (if present) for patients with nosebleeds. (7a) The clinician should perform, or should refer to a clinician who can perform, nasal endoscopy to identify the site of bleeding and guide further management in patients with recurrent nasal bleeding, despite prior treatment with packing or cautery, or with recurrent unilateral nasal bleeding. (8) The clinician should treat patients with an identified site of bleeding with an appropriate intervention, which may include one or more of the following: topical vasoconstrictors, nasal cautery, and moisturizing or lubricating agents. (9) When nasal cautery is chosen for treatment, the clinician should anesthetize the bleeding site and restrict application of cautery only to the active or suspected site(s) of bleeding. (10) The clinician should evaluate, or refer to a clinician who can evaluate, candidacy for surgical arterial ligation or endovascular embolization for patients with persistent or recurrent bleeding not controlled by packing or nasal cauterization. (11) In the absence of life-threatening bleeding, the clinician should initiate first-line treatments prior to transfusion, reversal of anticoagulation, or withdrawal of anticoagulation/antiplatelet medications for patients using these medications. (12) The clinician should assess, or refer to a specialist who can assess, the presence of nasal telangiectasias and/or oral mucosal telangiectasias in patients who have a history of recurrent bilateral nosebleeds or a family history of recurrent nosebleeds to diagnose hereditary hemorrhagic telangiectasia syndrome. (13) The clinician should educate patients with nosebleeds and their caregivers about preventive measures for nosebleeds, home treatment for nosebleeds, and indications to seek additional medical care. (14) The clinician or designee should document the outcome of intervention within 30 days or document transition of care in patients who had a nosebleed treated with nonresorbable packing, surgery, or arterial ligation/embolization. The policy level for the following recommendation, about examination of the nasal cavity and nasopharynx using nasal endoscopy, was an option: (7b) The clinician may perform, or may refer to a clinician who can perform, nasal endoscopy to examine the nasal cavity and nasopharynx in patients with epistaxis that is difficult to control or when there is concern for unrecognized pathology contributing to epistaxis.

Hereditary hemorrhagic telangiectasia: diagnosis and management from the hematologist's perspective.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. The diagnosis of hereditary hemorrhagic telangiectasia is clinical, based on the Curaçao criteria. Genetic mutations that have been identified include ENG, ACVRL1/ALK1, and MADH4/SMAD4, among others. Patients with HHT may have telangiectasias and arteriovenous malformations in various organs and suffer from many complications including bleeding, anemia, iron deficiency, and high-output heart failure. Families with the same mutation exhibit considerable phenotypic variation. Optimal treatment is best delivered via a multidisciplinary approach with appropriate diagnosis, screening and local and/or systemic management of lesions. Anti-angiogenic agents such as bevacizumab have emerged as a promising systemic therapy in reducing bleeding complications but are not curative. Other pharmacological agents include iron supplementation, antifibrinolytics and hormonal treatment. This review discusses the biology of HHT, management issues that face the practising hematologist, and considerations of future directions in HHT treatment.

MACULAR PIGMENT DISTRIBUTION RESPONSES TO HIGH-DOSE ZEAXANTHIN SUPPLEMENTATION IN PATIENTS WITH MACULAR TELANGIECTASIA TYPE 2.

PURPOSE: To analyze macular pigment (MP) amount and distribution in patients with macular telangiectasia Type 2 receiving oral zeaxanthin supplementation in a randomized, open-label, interventional trial. METHODS: Eight macular telangiectasia Type 2 patients were randomized to 10 mg or 20 mg of zeaxanthin per day. At each visit, best-corrected visual acuity, contrast sensitivity, fundus biomicroscopy, color fundus photography, autofluorescence imaging, optical coherence tomography, and serum carotenoid levels were tested. Patients were assessed at baseline and after 6, 12, 18, and 24 months of zeaxanthin supplementation. Concentration of MP was analyzed and calculated from autofluorescence imaging obtained at 488-nm excitation wavelength. Serum carotenoid levels were obtained using high-performance liquid chromatography. RESULTS: The majority of patients had definite increases in the intensity of hypofluorescent ring of MP, but none of them deposited MP centrally at the fovea. Although some patients noted subjective improvements in vision, no objective improvements could be documented, and there were no changes in foveal optical coherence tomographic features. Yellowish, hypofluorescent crystals appeared in one patient's macular region with no change in visual acuity. These inner retinal crystals disappeared several months after discontinuing her 20-mg zeaxanthin supplement. CONCLUSION: Based on the current study, zeaxanthin supplementation does not result in any visual benefit in patients with macular telangiectasia Type 2 and does not reestablish a normal peaked distribution of MP in the fovea. One patient developed a novel, reversible, crystalline maculopathy in response to zeaxanthin supplementation that was reminiscent of canthaxanthin crystalline maculopathy.

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.

Hereditary haemorrhagic telangiectasia in a black adult male: case report.

Hereditary haemorrhagic telangiectasia, (HHT) or Rendu-Osler-Weber disease is a genetic autosomal dominant disorder that is characterised by telangiectasias, (small vascular malformations), in mucocutaneous tissues and arterial venous malformations, (AVMs), in various internal organs. Although HHT is relatively common in whites, the disorder has been reported to be rare in people of black African descent. Majority of HHT patients present with recurrent epistaxis, which in a significant proportion of patients is severe, warranting repeated blood transfusions and iron supplementation. Telangiectasias are most frequent on the tongue, hands, nose, lips and the gastrointestinal tract (GIT). AVMs occur in internal organs, particularly the lungs, brain, and the liver. Early and correct diagnosis of HHT is crucial as patients derive benefit from certain specific treatment modalities. Besides, AVMs which occur in various organs pose serious complications that may lead to death and therefore require early detection. We report a 55 year old black African male with HHT who presented with severe recurrent epistaxis and haematochezia leading to severe anaemia requiring repeated blood transfusions. His son, daughter and a maternal uncle experience milder recurrent epistaxis. The management of this patient and a brief review of the clinical features and management of HHT is presented. Our aim is to raise awareness of the occurrence of HHT in Kenya, in order to enhance early diagnosis and appropriate management.

Hereditary haemorrhagic telangiectasia: state of the art.

Hereditary haemorrhagic teleangiectasia (HHT) or Rendu-Osler-Weber disease is a genetic autosomal-dominant disorder characterised by the presence of vascular telangiectases in mucocutaneous tissues, visceral organs and the Central Nervous System. Pulmonary arteriovenous malformations have a variable incidence rate ranging between 15-33%, and the safest treatment is transcatheter embolotherapy. Haemmorrhages from the gastrointestinal tract occur in 10-40% of patients with HHT localized in duodenum and colon and can be treated with endoscopy and laser coagulation, but this procedure is not efficacious for vascular anomalies in small intestine since this site cannot be easily reached. The prevalence of cerebrovascular malformations in hereditary haemorrhagic telangiectasia patients is 5-27%, and there are several types described including telangiectasias, cavernous angiomas, arteriovenous malformations, and aneurysms. Cerebrovascular malformations can be treated by: neurovascular surgery, embolization, and stereotactic radiosurgery, but the appropriate course of action for dealing with asymptomatic cerebrovascular malformations is still debated. The most common symptom in HHT patients is epistaxis, which can sometimes be so profuse that it requires multiple transfusions and iron supplementation. Nose bleeds begin before 10 years of age and become more severe in later decades. A multitude of different treatments are available, tailored to the severity of epistaxis. These include: hormonal therapy with oestrogens, application of fibrine tissue sealant, laser coagulation, embolization and septal dermoplasty using Saunder's technique. Aim of this study is to review diagnostic and therapeutic techniques, since continuous growth and danger of these arteriovenous malformations require early diagnosis, adequate treatment, prolonged follow-up and screening of the family.

Cutis marmorata telangiectatica congenita: report of two persistent cases.

Cutis marmorata telangiectatica congenita (CMTC) is defined as a localized or generalized reticulated, blue-violet vascular network in skin that is present at birth. The evolution is characterized by rapid improvement within 2 years. Rarely the lesions do not improve very much with age. Few reports include long-term follow-up of CMTC. We report two patients with persistent CMTC, including one with nervous breakdown and failure of laser treatment. The cause and incidence of persistent CMTC is unknown. Parents can be counseled that over time the lesions of CMTC may or not improve. There seems to be no predictive clinical sign. CMTC is usually a benign condition and therapy is rarely discussed. Treatment of persistent CMTC seems difficult and the effectiveness of laser therapy needs to be evaluated.

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.

Clinical spectrum of hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease).

Hereditary hemorrhagic telangiectasia (Osler-Weber-Rendu disease) is an autosomal dominant, systemic fibrovascular dysplasia in which telangiectases, arteriovenous malformations, and aneurysms may be widely distributed throughout the body vasculature. Major clinical manifestations include: recurrent bleeding from mucosal telangiectases and arteriovenous malformations; hypoxemia, cerebral embolism, and brain abscess due to pulmonary arteriovenous fistulas; high-output congestive heart failure and portosystemic encephalopathy from hepatic arteriovenous malformations; and a variety of neurologic symptoms due to central nervous system angiodysplasia. Therapy is primarily supportive, consisting of iron supplementation and blood transfusion. Septal dermoplasty and oral estrogens may allow prolonged remission of epistaxis, but permanent surgical cure of gastrointestinal bleeding is rarely feasible because of diffuse angiodysplasia of the alimentary tract. Ligation, resection, or embolization may be indicated for pulmonary arteriovenous fistulas. The prognosis and survival of patients with hereditary hemorrhagic telangiectasia are favorable, providing treatable complications are accurately diagnosed.