Graham Hughes1 and Shirish Sangle2
(1)
The London Lupus Centre, London Bridge Hospital, London, UK
(2)
Louise Coote Lupus Unit, St Thomas’ Hospital, London, UK
Abstract
One of the major features distinguishing Hughes Syndrome from other clotting disorders is the involvement of arteries.
One of the major features distinguishing Hughes Syndrome from other clotting disorders is the involvement of arteries.
The spectrum of arterial involvement ranges from acute obstruction, leading to infarction and gangrene, through the focal stenoses almost characteristic of Hughes Syndrome, to generalised “accelerated” atheroma, currently attracting the attention of researchers.
10.1 Peripheral Arterial Thrombosis
One of the bizarre features of the disease is the sudden – without warning – peripheral artery thrombosis – most commonly in the lower limb (Fig. 10.1).
Figure 10.1
Right femoral artery occlusion in a patient with Hughes Syndrome. No femoral artery seen on the left side due to complete occlusion
One of my first patients with this presentation was the previously fit 19-year-old, rugby-playing son of the vice-chancellor of a UK university, who developed acute femoral artery thrombosis with peripheral ischaemia.
Arterial gangrene affecting the hands is unusual, though can be seen in patients with widespread “catastrophic” APS.
The unique picture of arterial thrombosis, seen in Hughes Syndrome, can even affect the aorta, and a number of cases of aortic arch syndrome mimicking Takayasu’s arteritis have been recorded (Fig. 10.2).
Figure 10.2
Right subclavian artery occlusion mimicking Takayasu’s Disease in a patient with Hughes Syndrome
10.2 Internal Organs
Acute renal artery occlusion with renal ischaemia can be the presenting manifestation of APS.
Involvement of all major arteries has been described, including, of course, stroke, as well as retinal artery thrombosis, pituitary thrombosis, liver infarction, hip joint, gut (one of our patients presented with infarction of several feet of intestine) bone marrow and skin.
10.3 Focal Stenotic Lesions
These have now been described in many sites, including brain arteries, carotid, renal and celiac artery.
Renal artery stenosis, in particular, may be a prominent feature (Fig. 10.3).
Figure 10.3
Renal Angiogram showing right renal artery stenosis in Hughes Syndrome
The stenotic lesions are completely different from those seen in atherosclerotic disease and fibro-muscular hyperplasia. They are localised, the remainder of the arterial tree (including the aorta) being smooth and usually free from the irregularities seen in atheroma.
Renal artery stenosis can lead to hypertension – to be discussed in the next chapter.
Whilst screening angiographically for renal artery stenosis, we came upon another lesion – celiac artery stenosis (Fig. 10.4). A number of these patients (though not all) suffered from the classic features of mesenteric angina, with abdominal pain following at an interval after a large meal.
Figure 10.4
Magnetic resonance arteriogram showing celiac artery stenosis in Hughes Syndrome
The aetiology of these focal lesions remains uncertain, though localised thrombosis does appear to be the most likely cause. It is possible (though unproven) that such local lesions could lead to arterial wall weakness: Interestingly, a small number of cases of arterial aneurysm formation have been reported in association with APS.
10.4 Accelerated Atheroma
A topic of active research is the possible link between antiphospholipid antibodies and accelerated arterial disease.
It is well known, for instance, in lupus patients, that early onset arterial disease can be a major problem – so much so that lupus is sometimes referred to as the “new diabetes”.
The causes of this feature remain uncertain – steroids, kidney disease and inflammation have all been looked at but none alone totally explains the link.
One line of research follows the observation that certain aPL can cross-react with oxidised low-density lipoproteins – a key player in atheroma formation.
Studies are in progress to assess whether aPL-positive lupus patients are more at risk from accelerated arterial disease.
An obvious question concerns the prevalence of this feature in APS patients (who have never taken steroids, who have no renal disease and who have no clinical evidence of chronic inflammation).
And, interestingly, initial studies do suggest early arterial disease in some of these patients – studies using indirect methods to look at arterial function, it must be said.