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CASE IN POINT: CLINICS IN INTERNAL MEDICINE
Year : 2017  |  Volume : 3  |  Issue : 4  |  Page : 228-230

Hereditary hemorrhagic telangiectasia with severe anemia and recurrent CNS infections


Department of General Medicine, Tirumala Hospitals, Vizianagaram, Andhra Pradesh, India

Date of Web Publication7-Jul-2017

Correspondence Address:
Peesapati Nrushen
Department of General Medicine, Tirumala Hospitals, Vizianagaram, Andhra Pradesh
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/astrocyte.astrocyte_4_17

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  Abstract 

Hereditary hemorrhagic telangiectasia also known as Osler–Rendu–Weber disease is a rare autosomal dominant disorder affecting small vessels of multiple systems whose main pathological change is the presence of abnormal arteriovenous communications. It usually presents as skin and mucosal telangiectasia, epistaxis, gastrointestinal bleeding, and visceral arteriovenous malformations. Although epistaxis and gastrointestinal blood loss can result in anemia, patients with hereditary hemorrhagic telangiectasia rarely present with severe anemia and central nervous system (CNS) infections. Here, we report the case of a 57-year-old man who presented with severe anemia resulting in congestive cardiac failure with a history of recurrent blood transfusions and recurrent CNS infections who was ultimately diagnosed as hereditary hemorrhagic telangiectasia with recurrent epistaxis as a cause of his severe anemia.

Keywords: Anemia, arteriovenous fistula, epistaxis, hereditary hemorrhagic telangiectasia, Rendu–Osler–Weber


How to cite this article:
Nrushen P, Sunitha S, Sivaram P V. Hereditary hemorrhagic telangiectasia with severe anemia and recurrent CNS infections. Astrocyte 2017;3:228-30

How to cite this URL:
Nrushen P, Sunitha S, Sivaram P V. Hereditary hemorrhagic telangiectasia with severe anemia and recurrent CNS infections. Astrocyte [serial online] 2017 [cited 2020 Aug 12];3:228-30. Available from: http://www.astrocyte.in/text.asp?2017/3/4/228/209930


  Introduction Top


Hereditary hemorrhagic telangiectasia (HHT), first described in 1865, is an autosomal dominant disorder causing abnormal capillary dilatations or connections called telangiectasia between arterioles and venules. Vascular lesions in HHT may also present as arteriovenous malformations (AVM) or aneurysms, especially found in the brain, lungs, liver, and gastrointestinal system (visceral AVMs). Such connections remain usually asymptomatic and can be life threatening if ruptured. HHT is usually not considered early in the differential diagnosis of severe anemia.[1] A careful history with thorough examination is required to diagnose the disease.

The diagnosis is based on Curacao criterion [2] established in 1999–2000 which include

  1. Spontaneous, recurrent epistaxis. Nocturnal nosebleeds heighten concern for HHT
  2. Mucocutaneous telangiectasia, especially on the lips, tongue, oral cavity, fingers, and nose
  3. Internal AVM (s) (pulmonary, cerebral, hepatic, gastrointestinal, spinal)
  4. First-degree relative with HHT according to these criteria.


Definite diagnosis: 3 or more criteria present

Possible diagnosis: 2 criteria present

Unlikely diagnosis: <2 criteria present

The clinical profile of HHT, a rare disease with a classic presentation, quite rarely includes severe anemia and recurrent central nervous system (CNS) infections. Patients with HHT present normal hemostasis and platelet function, and the recurrent bleeding is therefore related to the telangiectasia. Anemia can be due to one or both factors: recurrent epistaxis and gastrointestinal bleeding; recurrent CNS infections are caused by septic emboli from pulmonary AVMs.


  Case Report Top


A 57-year-old male with a history of recurrent blood transfusions was admitted with complaints of dyspnea on exertion, easy fatigability, and pedal edema since 1 month. He also had a history of recurrent spontaneous epistaxis since his childhood, i.e., around 3–4 episodes per month. The patient gave a history of surgical intervention for left parietotemporal cerebral abscess in 1994 evidenced by gliosis in recent imaging. He was diagnosed having Pott's spine in 2005 and underwent surgery. Presently, he was on antituberculous therapy since December 2015 for suspected tuberculoma in cerebral parenchyma.

On probing, the patient admitted that some of his family members also had recurrent epistaxis and telangiectasia over the fingers and tongue [Figure 1] and [Figure 2]. Neither the patient nor his family members were labelled with any specific diagnosis before this presentation. Detailed family history was taken to document the mode of inheritance (Pedigree chart of patient, [Figure 3]).
Figure 1: This 57-year-old male presented with multiple telengectasias over the dorsum of his tongue.

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Figure 2: The patient also had a number of telengectasias on his finge

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Figure 3: The pedigree chart of the patient drawn to document the mode of inheritance.

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Family history clearly revealed that the epistaxis had occurred for generations in a pattern indicative of autosomal dominant inheritance. Physical examination revealed marked pallor, bilateral pitting type of pedal edema, and raised jugular venous pressure. On careful observation, capillary telangiectasia were present on the dorsum of tongue and finger tips.

On auscultation, there was continuous murmur of grade 5/6 heard over the left interscapular region, which was suggestive of AVM and was confirmed by color Doppler imaging.

Hence, in view of a history of recurrent epistaxis, autosomal dominant inheritance, and mucocutaneous and visceral telangiectasia, a diagnosis of HHT was made (Curacao criteria). Laboratory investigations demonstrated severe microcytic microchromic anemia, normal thrombocytes and a normal coagulation profile. Upper gastrointestinal endoscopy revealed multiple telangiectatic lesions in the duodenum, suggesting visceral AVMs.


  Discussion Top


HHT is a rare disorder with a prevalence of 1 in 5000 to 10000 with an autosomal dominant transmission, despite the fact that approximately 20% of the cases may not have a family history.[3] It is thought that the abnormal vessels in HHT develop because of aberrant transforming growth factor signaling at some stage during vascular development and mutations of HHT-associated genes. HHT is divided in to four types on genetically.[4] It has been proposed that, in the case of HHT, disease severity is more pronounced in HHT1 compared to HHT2, with an earlier age of onset for epistaxis, appearance of telangiectasia, and higher incidence of pulmonary AVMs. HHT1 is caused by mutations in the gene, ENG (endoglin), encoding endoglin on chromosome 9q. HHT2 occurs due to mutations in the gene ALK-1 (activin receptor-like kinase 1), encoding activin receptor-like kinase 1 on chromosome 12q13. The clinical manifestations of HHT are known to be variable and age-dependent. Epistaxis is the first and most common symptom (90% of patients), 80% of the patients have telangiectasia of the skin, lip, or mouth. These usually do not cause serious illness; however, patients may have a variety of serious complications due to the vascular involvement of internal organs, such as the gastrointestinal tract (15%), lungs (30%), hepatic AVMs (<30%), central nervous system (10%), and spinal AVMs (1%).

Patients need thorough investigations and close follow-up for visceral AVMs because each may contain clinically silent lesions that can result in sudden morbidity or death. Pulmonary AVMs may present with dyspnea, cyanosis, massive hemoptysis, and hemothorax. For clinical relevance, the diameter of the artery of the pulmonary AVM must be ≥3 mm. Pulmonary AVMs cause right-to-left shunts resulting in hypoxemia.

Our patient had a history of recurrent CNS infections [Figure 4] and [Figure 5], which can be due to absence of a filtering capillary bed allowing emboli to reach the systemic circulation.[5]
Figure 4: CT showing ring enhancing lesion with perilesional edema (tuberculoma) and left temporoparietal gliosis.

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Figure 5: MR imaging and spectroscopy of the ring enhancing le

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Cerebral AVMs can lead to headaches, seizures, strokes, transient ischemic attacks, and both intracerebral and subarachnoid hemorrhage. Gastrointestinal bleeding (common from the stomach and duodenum) can result in iron deficiency anemia or acute gastrointestinal hemorrhage.

Treatment of hereditary hemorrhagic telangiectasia

No definitive treatment is available for HHT. Appropriate management depends on clinical manifestations and site of the disease and remains largely symptomatic. Management options for cutaneous lesions include electrocauterization with diathermy, sclerotherapy, or laser therapy. AVMs need intervention either as coiling or by clipping; treatment for bleeding is symptomatic and can require iron therapy and blood transfusions. Aspirin and other medicaments that impair hemostasis are contraindicated in such cases.

Recent advances: Role of bivacizumab

Bivacizumab is a humanized monoclonal anti-VEGF antibody. It inhibits vascular endothelial growth factor A (VEGF-A). VEGF-A stimulates angiogenesis in a variety of diseases including HHT. It significantly reduces epistaxis, causes improvement in gastrointestinal blood loss, and hepatic AVMs in latest studies. It is given at a dose of 5 mg/kg body weight as intravenous infusion for 4 weeks.[6] We could not give it to our patient due to economic constraints.


  Summary Top


In summary, although HHT is a rare disease, it needs to be suspected in a patient with recurrent bleeding and normal coagulation. Moreover, it can be easily recognized by careful family history and close observation for telangiectasia. Incorrect diagnosis postpones appropriate therapeutic measures and increases the possibility of chronic complications which can remain unrecognized till advanced stages of the disease.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Šupak V, Bilić-Zulle L, Duletić-Naćinović A, Fičić E. Case report of hereditary hemorrhagic telangiectasia with severe anemia. Biochem Med 2008;18:106-14.  Back to cited text no. 1
    
2.
Shovlin CL, Guttmacher AE, Buscarini E, Faughnan ME, Hyland RH, Westermann CJ, et al. Diagnostic criteria for hereditary hemorrhagic telangiectasia (Rendu-Osler-Weber syndrome). Am J Med Gene 2000;91:66-7.  Back to cited text no. 2
    
3.
Deshpande P, Bhat S, Karmarkar A. Hereditary Haemorrhagic Telangiectasia-A Rare Cause of Severe Anaemia. J Assoc Physicians India 2014;62:48-51.  Back to cited text no. 3
    
4.
te Veldhuis EC, te Veldhuis AH, van Dijk FS, Kwee ML, van Hagen JM, Baart JA, et al. Rendu-Osler-Weber disease: Update of medical and dental considerations, Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2008;105:e38-e41.  Back to cited text no. 4
    
5.
Bose P, Holter JL, Selby GB. Bivacizumab in Hereditary Hemorrhagic Telangiectasia. N Engl J Med 2009;360:2143-4.  Back to cited text no. 5
    
6.
Solanki SP, Taylor C, Robertson I. Hereditary haemorrhagic telangiectasia manifesting as subdural empyema. Br J Neurosurg 2016;30:356-8.  Back to cited text no. 6
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]



 

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