We present a prepubertal male cystic fibrosis patient with high circulating oestrogen levels (as a consequence of severe cystic-fibrosis-related hepatobiliary disease) who subsequently developed a large pelvic arteriovenous malformation. This has not previously been described in patients with cystic fibrosis, despite the association between high oestrogen levels and arteriovenous malformations. The aetiology and treatment options of arteriovenous malformations are discussed.
- arteriovenous malformation
- cystic fibrosis
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Although life expectancy in cystic fibrosis (CF) continues to improve, most patients still have considerable morbidity from multiorgan disease. Vascular abnormalities are well known in CF, and usually involve the bronchopulmonary or portal circulation. It is also recognised that arteriovenous malformations (AVMs) occur more frequently where there are high levels of circulating oestrogens, a state which can occur in CF patients with advanced liver disease. Despite this, AVMs have not previously been described in CF patients. We present a case of a pelvic AVM developing in an 18-year-old CF patient with delayed puberty and severe respiratory and hepatobiliary disease. The pathogenesis, diagnosis, and treatment of these lesions are discussed.
An 18-year-old male CF patient had secondary biliary cirrhosis noted aged 8 years, and subsequently developed oesophageal varices. Following this he had several upper gut bleeds and multiple courses of sclerotherapy. By the age of 14 years his main problem was symptomatic massive splenomegaly which was corrected by splenectomy. Male hormone treatment (Sustenon 250) was commenced for delayed puberty (no pubic hair and Tanner stage II genitalia) at 16 years, given by intramuscular deltoid injection monthly for six doses. Despite this, he still has no signs of secondary sexual development and recent assay of his sex hormones reveal him to have very low luteinising hormone, follicle-stimulating hormone, and testosterone levels, in keeping with delayed puberty. Furthermore, he had a normal serum zinc level but raised oestradiol level secondary to his severe liver disease.
At 18 years a painful lump appeared on his left buttock and examination revealed a large firm swelling affecting the whole of the left buttock and to a lesser extent the right buttock and lumbar region (figure 1). The swelling was non-pulsatile, warm, mildly tender, and not fixed to the overlying skin. Rectal examination revealed no evidence of haemorrhoidal varices. Computed tomography (CT) showed a large vascular lesion involving the gluteal muscles, the skin and subcutaneous tissues (figure 2). Angiography demonstrated extensive arteriovenous communications within the pelvic and gluteal areas fed by both internal iliac systems and a large median sacral artery.
Arteriovenous malformations can be either congenital or acquired. In the primitive mesenchyme interlacing blood spaces are partly absorbed and coalesce, and separate venous and arterial conduits appear around the capillary network. Developmental arrest or misdirection causes formation of communicating channels between mature arteries and veins, associated with the appearance of supernumerary branches due to overgrowth of vascular elements. Increase in size of congenital AVMs is due to engorgement and ageing of the component elements. Acquired AVMs are rarer and may be due to trauma: Natali1 described a woman who developed a pelvic AVM a year after trauma to her buttock. However, some authors believe that trauma simply calls to attention congenital lesions.2
The majority of AVMs involve the extremities, head and neck, and lungs. Pelvic AVMs are very rare (< 2% of the total)3; there are less than 60 cases described in the world literature. Most are diagnosed in the second and third decades of life.4Symptoms depend on the size and site of the lesion: pelvic lesions may grow to a large size before they occur. Paradoxically, systemic haemodynamic effects rarely occur because communications are multiple, tortuous, and narrow, maintaining peripheral vascular resistance. High output cardiac failure has been observed only in very bulky lesions and in pelvic lesions during pregnancy.6 7
Angiographic investigation demonstrates the flow characteristics of the lesion, feeding arteries, draining veins, and their relationship to the normal circulation. Magnetic resonance imaging or CT will reveal the extent of the lesion. Treatment requires a team approach and a combination of pre-operative embolisation and surgery is advocated, with complete excision of isolated lesions resulting in the best cure rates.8 Recurrence is common if there is simply ligation of feeding vessels. However, asymptomatic static lesions can be monitored and may not require active treatment.
Two-thirds of AVMs occur in women and there is a relationship to parity, suggesting an effect of fluctuating oestrogen and progesterone levels on the vascular wall,5 and oophorectomy may lead to regression of an AVM.9 Despite the association between AVMs and high oestrogen levels, oestrogen blocking agents have not been used to treat these lesions.
Management of pelvic AVMs
asymptomatic non-enlarging lesions: monitor only
indications for intervention: relative (pain, functional impairment) or absolute (haemorrhage, high output cardiac failure)
percutaneous arterial embolisation
surgical devascularisation ± excision of mass
percutaneous arterial embolisation to diminish size of AVM then surgical excision
Our patient did not have zinc deficiency which has been associated with delayed puberty in CF,10 but did have severe liver disease and high oestrogen levels, which may have contributed to the condition. To our knowledge there have been no previous case reports of AVMs in patients with CF. As survival prospects for patients with CF continue to improve, there will be more individuals with severe CF-related liver disease and therefore it is possible that more of these unusual complications will occur within this patient group. In our patient, a combination of embolisation with surgical resection and plastic reconstruction of the buttocks would be required. Indications for this would be haemorrhage, heart failure, skin breakdown, or pain intolerable to the patient. Since he has many concomitant problems which limit his survival prospects, surgery would be a hazardous undertaking and therefore a conservative approach has been adopted.