Indian Journal of Dermatology, Venereology and Leprology Medknow Publications on behalf of The Indian Association of Dermatologists, Venereologists and Leprologists (IADVL) ISSN: 0378-6323 EISSN: 0973-3922 Vol. 75, Num. 1, 2009, pp. 100-100

Indian Journal of Dermatology, Venereology and Leprology, Vol. 75, No. 1, January-February, 2009, pp. 100

Net Case

Osler-Weber-Rendu syndrome: A case report with familial clustering

Grover Sanjiv, Grewal RS, Verma Rajesh, Sahni H, Muralidhar R, Sinha Preema

Department of Dermatology, Armed Forces Medical College and Command Hospital, Pune - 411 040
Correspondence Address:Department of Dermatology, Armed Forces Medical College, Pune - 411 040, sanjivgrover@rediffmail.com

Code Number: dv09032

Abstract

Keywords: Familial, Hereditary, Telangiectasia

Introduction

Case Report

A 45-year-old postmenopausal lady born to nonconsanguineous parents presented with multiple red raised lesions on the tongue and both hands of almost 25 years duration. She also had breathlessness on exertion and easy fatig ability since 15 years. She had a history of recurrent spontaneous severe bleeding from the lesions, especially from those on the tongue due to which she had to receive multiple blood transfusions in the past two decades, and multiple episodes of mild epistaxis, palpitations, and frequent blackouts. There was no history of bleeding gums, abdominal pain, bleeding rectum, headaches, seizures, visual disturbances, hemoptysis, menorrhagia, or bluish discoloration of fingertips or nose. There was history of similar lesions being present in 11 of her immediate family members [Figure - 1]. Her three elder sisters died of severe bleeding from such lesions in the mouth and hands; also, her father suffered from hemiplegia.

Clinical examination revealed pallor and absence of organomegaly. Dermatologically, multiple erythematous macular blanchable lesions on both palms, multiple erythematous compressible nonpulsatile papulonodular lesions on the tongue, and multiple petechiae over the palate [Figure - 2] were evident.

Investigations revealed microcytic hypochromic anemia, normal reticulocyte count, and normal coagulation profile. Serum for antinuclear antibody (ANA), urine for hemoglobinuria, and Sickling test were negative. Abdominal ultrasonogram, chest skiagram, and fundoscopy were unremarkable. Angiogram of carotids revealed multiple telangiectatic lesions in the tongue fed by bilateral lingual arteries, while those in the palate were fed by sphenopalatine branch of internal maxillary artery (IMA) [Figure - 3]. The lesions showed early venous drainage with persistence of stain in the parenchymal phase. Upper GI endoscopy revealed multiple petechiae in the abdominal wall. Neither colonoscopy nor abdominal, pulmonary, and renal angiograms revealed any AVMs in other organ systems.

Discussion

While Henri Rendu (1896), Sir William Osler (1901), and Frederick Parks Weber (1907) emphasized and published detailed observations of the syndrome which bears their names, it was Sutton (1864) who first described Osler-Weber-Rendu disease and Benjamin Guy Babington (1865) was the first to note its familial nature.

A number of variants of HHT have been described in literature. HHT type-1 and type-2 are due to defective endoglin ( ENG ) and activin like receptor kinase ( ALK1 ) genes, respectively. Mutations of ENG are located on the long arm of chromosome 9 (9q33-34), whereas ALK1 mutations are on the long arm of chromosome 12 (12q13). ^[2],[3] HHT type-3 involves mutations of the long arm of chromosome 5 (5q31.1-32) and type-4 maps to the short arm of chromosome 7 (7p14). ^[4],[5] A HHT-juvenile polyposis overlap syndrome due to mutations of SMAD4 has also been described. ^[6] Patients with the HHT type-1 genotype have higher prevalence of pulmonary and cerebral AVMs, and more severe GI bleeding than in those with the HHT type-2 genotype. Conversely, the prevalence of hepatic AVMs is higher in patients with HHT type-2 than in those with HHT type-1. ^[7] Although the precise mechanism remains poorly understood, bleeding tendency in HHT is attributed to localized vessel wall weakness.

Diagnosis is based on the four components of the Curaηao criteria, established by the Scientific Advisory Board of the HHT Foundation International, Inc., viz. (1) epistaxis: spontaneous and recurrent; (2) telangiectasias: multiple, at characteristic sites, including lips, oral cavity, fingers, and nose; (3) presence of internal lesions: GI telangiectasia, pulmonary, hepatic, cerebral, and spinal AVMs; and (4) family history: first-degree relative with HHT according to these criteria. The diagnosis is considered definite if any three of the above mentioned criteria are present and possible if any two of the criteria are present. The diagnosis is unlikely if less than two criteria are present. ^[8] Our case was unique with the presence of all four criteria confirming the diagnosis. In the absence of pulmonary AVMs, her symptomatology is attributed to anemia resulting from frequent bleeding from her vascular lesions.

The varied treatment modalities include estrogen, Î-amino-caproic acid, cryotherapy, cautery, infrared coagulation, radiofrequency, pulse dye laser, Nd-YAG laser, and surgical ablation - all of which may be fraught with risks. ^{[9],[10],[11],[12],[13]}

Asymptomatic pulmonary and CNS AVMs and their hemorrhagic or embolic complications, viz. brain abscess and stroke are responsible for most of HHT′s 10% mortality rate. It is crucial that a long-term follow-up for identification of potential complications is maintained and patients are counseled regarding the autosomal dominant nature of the condition.

Though cases have been reported with digital and mucocutaneous telangiectasias, ^[14] our case is particularly unique as it had all the four criteria for diagnosis and that 12 members of the same family could be identified with this disease.

References

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