A rare and misdiagnosed bleeding disorder: hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease in which abnormal communications between arteries and veins, the so-called telangiectases, occur in the skin, mucosal surfaces, and solid organs [1]. Small telangiectases on the face may present an important cosmetic problem, but larger lesions can be a source of chronic blood loss, systemic emboli, hypoxemia, hepatic dysfunction, and high-output cardiac failure. HHT is an uncommon disease with an overall frequency calculated between 1 per 5000 and 10 000 persons [2]. In the literature, over the past 160 years, many disorders have been attributed to HHT but the criteria for a definite diagnosis have been established only few years ago. The clinical diagnosis of HHT is based on the presence of at least three of the following characteristics: recurrent epistaxis, mucocutaneous telangiectases, evidence of autosomal dominant inheritance, and visceral arteriovenous malformations [3]. Nomention of illnesses which could be reasonably attributed to HHT or a similar disease can be found in the early medical discourses of Hippocrates, Galenus, Avicenna. Moreover, HHT or recurring nosebleeding are not mentioned in the Bible, nor in the ancient writings from Egypt, Greece and Rome. In 1865, an hereditary form of epistaxis was described for the first time in The Lancet; Benjamin Guy Babington, an English physician, published a report on a patient who suffered from nosebleeds since he was 8 years old, as was also his mother [4]. Previously, in 1864, Gawen Sutton had already described the case of a man with vascular malformations and recurrent hemorrhage but since he was an orphan, no information regarding the family was available [5]. The unusual association of multiple telangiectases on mucous membranes and the skin was observed both by John Wickham Legg in 1876 [6] and Henry Louis Marie Rendu in 1896 [7,8]. At the meeting of the Royal Medical and Surgical Society in London, Wickham Legg described a patient with familiar epistaxis and multiple small ‘nevi’ which developed during his lifetime. In his case report, Henry Rendu described a 52-year-old man with anemia and daily recurrence of nosebleeds since the age of 12 years whose father also had a history of melena; other hemorrhages were not present but Rendu described numerous small red spots on the nose, tongue and upper lips due to dilatation of superficial vessels (telangiectases). In the paper, two additional cases were described in a family in which epistaxis had occurred in seven members; both patients had nosebleeds from childhood together with telangiectases. The condition was not related to hemophilia. Subsequently, in the John Hopkins Hospital Bulletin in 1901, Sir William Osler, a famous Canadian physician, reported on three families with hereditary telangiectasia and hemorrhages [9]. In the first family, George B., a sailor aged 57, was admitted to the JohnHopkins Hospital with weakness, anemia and swelling of the feet. From childhood his father had had bleeding from the nose and cuts. His mother was healthy but two of his four brothers suffered from epistaxis. George had always been very anemic and often bled from an angioma on the lower lip and on the mucosa of the septum. His face, ears, nose, cheeks and lips presented numerous telangiectases. In the second family, William B., aged 55, reported bleeding episodes every day but was admitted to the hospital because of nausea, vomiting and abdominal pain from which he had suffered for several months. He also demonstrated numerous gastric telangiectases of 3–4 mm in diameter. He died of hematemesis 1 month later. In the third family, a 48-year-old woman, Inez MWC, had recurrent epistaxis since the age of 10 and multiple telangiectases on the face. Her hemorrhaging lasted from a few minutes to half an hour. Sir William Osler was quite fascinated by this hereditary disease and published other new case reports 6 years later [10] in which he also emphasized the curious relationship of angiomata or telangiectases with abnormalities of the liver. These reports were followed by further descriptions by Frederick Parkes Weber in The Lancet in 1907; thus the Correspondence: Carlo Sabbà, University Interdepartmental HHT Center, Chair of Emergency Medicine – Clinica Medica ‘A.Murri’, DIMIMP-University of Bari, Policlinico, Piazza Giulio Cesare 11, Bari 70124, Italy. Tel/fax: +39-080-5478708; e-mail: [email protected]