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
Although the description of the syndrome, its critical propensity to artery thrombosis (e.g. stroke) and the development of simple assays for its detection are “modern” in comparative medical terms, for some of us, progress seems slow.
24.1 Thirty Years Old
Although the description of the syndrome, its critical propensity to artery thrombosis (e.g. stroke) and the development of simple assays for its detection are “modern” in comparative medical terms, for some of us, progress seems slow. For example, in a recent, “YouGov”, survey, commissioned by the charity, Hughes Syndrome Foundation (www.hughes-syndromefoundation.co.uk), only 15% of the responding public had heard of Hughes Syndrome or APS.
Yet there are grounds for optimism. In the world of obstetrics, aPL testing after serial miscarriage and late pregnancy loss is becoming standard practice.
24.2 One in Five
A rough rule of thumb can be drawn from publications so far, relating to Hughes Syndrome (APS) (Fig. 24.1).
Figure 24.1
Major features of HS
Hughes Syndrome accounts for 1 in 5 of all cases of recurrent miscarriage.
It accounts for 1 in 5 cases of DVT.
It accounts for 1 in 5 cases of stroke in the under 45 year olds – a striking figure!
And in lupus? Some 1 in 5 have positive aPL tests, with the consequent thrombotic complications.
24.3 Also One in Five?
Recent reports have suggested that young (under 45) patients – particularly females – with myocardial infarction have underlying Hughes Syndrome – 40% in one series having positive tests for aPL.
In the world of neurology, epilepsy has been shown to be an important feature – one study showing that 1 in 5 cases of ideopathic teenage epilepsy were aPL positive.
24.4 Migraine
Perhaps the biggest “missing link” concerns migraine. Such a common and prominent symptom in so many Hughes Syndrome patients, migraine, in all its forms, has received surprisingly few major studies linking it with APS.
Yet the literature contains a significant number of reports linking migraine with stroke and with heart attack. This physician believes that APS could be a strong “missing link” between migraine and vascular disease.
24.5 What Else?
Bright students of medicine will have picked up on a number of leads, published in the literature, picked up in this short book, which “need further study”. Some are highlighted here.
24.6 The Pill
The danger of thrombosis on the oral contraceptive pill is well known. The significantly increased risk of an aPL-positive woman developing thrombosis on the pill is not.
The report that an aPL-positive woman smoker starting the oral contraceptive has a 200-fold increase of suffering a stroke and a 20-fold increased risk of heart attack is arresting and vitally important.
24.7 Orthopaedic Surgery
DVT following knee or hip surgery costs every country millions of pounds. Many orthopaedic units now carry out pre-operative blood tests for clotting tendencies such as Factor V Leiden deficiency and aPL – but not all.
Furthermore, the discovery that some cases of unexpected fracture and of hip necrosis could be due to ischaemia secondary to Hughes Syndrome opens up important lines of research.
24.8 Memory Loss
In the longer term, it may well be that memory loss will become the leading clinical feature of Hughes Syndrome. Certainly in clinical practice, it is a common and extremely worrying symptom in Hughes Syndrome patients (Fig. 24.2).
Figure 24.2
Memory loss in HS (Reproduced with kind permission from Understanding Hughes Syndrome, ISBN-978-1-84800-375-09Springer)
In busy clinical practice however, there is not the time, nor the personnel for in-depth memory and other psychiatric testing.
Yet this is one of the potentially most important findings of the syndrome – a serious, yet potentially reversible brain problem – an aspect of Hughes Syndrome which, with future careful psychometric studies, must come to be recognised for the important clinical symptom that it surely is.
24.9 Unexpected Fracture
Again, the reports of metatarsal fractures in some patients with Hughes Syndrome may turn out to be the tip of the iceberg. Already there are reports of other fractures – possibly on the basis of bone ischaemia.
Those working in osteoporosis have long recognised that some patients seem to fracture without evidence of demineralisation – perhaps a percentage of these will prove to have “sticky blood”.
24.10 Infertility
We hope that the next few years might provide more insights into a possible link between antiphospholipid antibodies (aPL) and infertility. There are a number of excellent research groups looking at aPL and their influence on placentation, embryogenesis and vascular supply in each pregnancy.
24.11 And in Lupus?
In my own subject, lupus, the discovery of the antiphospholipid syndrome has genuinely revolutionised management. Many lupus features previously thought to be inflammatory – and “steroid-requiring” – are now thought more likely to be due to aPL-related thrombosis.
In the brain, for example, many features previously thought to be inflammatory, “vasculitis” – including stroke, seizure, myelopathy, memory loss, visual disturbance – are almost certainly more likely to be aPL related.
In the kidney, one of the major indications for renal biopsy is to assess the extent of glomerular thrombosis.
In pregnancy, we now know that lupus itself is almost certainly not a cause of miscarriage – it is the subset with aPL who are at risk.
And in treatment, the description of the syndrome has tipped the focus just a little bit away from steroids and immunosuppressives towards a more logical consideration in some cases of aspirin, heparin or warfarin.
24.12 Education
The recent, “YouGov”, survey showed, as might be expected, that few members of the general public were aware of APS/Hughes Syndrome. Hopefully, this will change.
I remember a similar survey 40 years ago conducted by a TV company asking about awareness of lupus. Few of those interviewed in Trafalgar Square had ever heard of lupus. How that has changed!