Professor Hughes' blog ...
June 2010
May 2010
April 2010
March 2010
February 2010
January 2010
December 2009
November 2009
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March 2009
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January 2009
June 2010
June this year has flashbacks to 2009. Despite the long grey winter and spring, this month has improved by the week. As I write this, in the last days of the month, we are in the throes of a sun-drenched Wimbledon and (can it be true?) the beginning of a drought!
Our annual medical meeting “Ten Topcs” is to be held as usual at the start of July, this year on the 1st and 2nd. Two hundred doctors registered for this wonderful meeting. International guest speakers. Catering planned. Nothing can go wrong? (Last year was just as hot: the air conditioning in the lecture theatre at St Thomas’ Hospital failed.)
As usual, quite a chunk of the two day meeting will be devoted to Lupus and to Hughes Syndrome, with newer aspects of treatment and ‘hot topics’ including, for example, new data on how antiphospholipid antibodies might cause thrombosis and miscarriage. My own talk this year is on an interesting question that is “are there circumstances other than thrombosis where anticoagulation might be beneficial?”. Today’s ‘patient of the month’ could be one such example.
Patient of the Month: “I failed a job application of Wendy’s”
Mrs P.A., a 40 year old American lady had been diagnosed with Hughes Syndrome following three miscarriages and a possible previous thrombosis, first treated with warfarin but now on aspirin.
At first things had gone well, but more recently she had slowed down, partly because of aches and pains in both hips and possibly more seriously, because of increasing chest discomfort on walking up slopes.
Hip x-rays were normal, but cardiac testing showed slightly impaired blood supply to the heart muscle, despite normal–looking coronary arteries.
Blood tests revealed high anticardiolipin (aCL) levels and, a ‘blast from the past’, a false positive test for syphilis.
It was decided to change treatment to warfarin. Not only was there an immediate improvement in the chest discomfort (and in the heart tests), but to everyone’s surprise, the hip pains disappeared as well!
What is this patient teaching us?
Firstly the ‘false positive’ test for syphilis. One of the early serum tests for syphilis (in fact one of the very earliest test in immunology) was named after its inventor, the “Wasserman reaction” or “WR”. At first, a positive “WR” test was thought to indicate infection with syphilis. Later it was recognised that “false positive WR” tests could occur in other individuals, mainly lupus patients. We now know that those unfortunate lupus patients, including our 40 year old, who as an innocent 16 year old was devastated by being turned down for a job in Wendy’s fast food outlet because of a positive WR test. In retrospect, of course, she was carrying the aPL antibody. A close friend of my wife and I, herself a lupus patient from Cyprus, once told me how she and her husband had once planned a life in America, but were turned down by a (false) positive WR test.
There is another lesson to be learnt from this story. We have always suspected that in many cases the telltale antibodies appear long before the disease. In a recent widely reported study from America, a group in Oklahoma traced the records (and blood samples) of US military recruits. As might be guessed, a number of lupus patients with previous army records had had positive lupus tests years (and sometimes decades) prior to clinical symptoms.
The failed “Wendy teenager” might be a similar example. But even more interesting for the medical sleuths is the improvement not only in the chest pains, but also in the bilateral hip pain.
In previous publication and ‘blogs’ I have attempted to emphasise how important the syndrome might be in the world of cardiology. We have, for example, seen a number of patients with angina-like pain in whom the coronary main motorways seem clear (sometimes called rather mysteriously “Syndrome X)”. Presumably the ‘sticky blood’ is affecting the smaller vessels in the heart, the highways and byways rather than the coronaries, which are more usually affected in the other disease, atheroma.
And the hips? Interestingly further tests showed the hips as having early “avascular necrosis”, too subtle to be picked up on x-ray, but clearly shown on MRI. Now avascular necrosis “AVN” is a condition which results from impaired blood supply to the head of the femur and a number of cases have been seen in Hughes Syndrome.
I believe it is just conceivable that in Mrs P.A.’s case the condition was early enough for the symptoms to improve with better blood supply. Here’s hoping a bright young rheumatology of orthopaedic research fellow will follow this lead up!
May
2010
Spring at last!
This year has been so different from last – cold and
grey. It was May 15th before I finally shed my overcoat –
but then I’m a wimp. Finally, things did change –
dramatically, and today (May 24th) the temperature has reached
83 degrees in London. Late catch-up in the garden. Our one
year old puppy, Lucy, (a miniature Schnauzer) is in her element
– her moustache and eyebrows covered in new-mown grass.
In Britain, April
saw the general election bring a new coalition government.
I happened to be in central London (with colleagues at the
opening of the excellent renovated Florence Nightingale museum
at St Thomas’ Hospital) the evening after the election
results.
There was certainly
a ‘buzz’ in town, with big black cars scurrying
around Westminster, and TV reporters camped on college green.
This weekend we
stayed with our daughter Sarah and her family in Winchester.
We never fail to enjoy the beauty of this historic town –
the nation’s capital long before London.
Sarah’s youngest
was singing in the choir at morning service. We soaked up
the wonderful music, the atmosphere. It is easy to see how
much of an impact such a magnificent cathedral must have had
on the population in the middle ages – the soaring architecture,
the crimson and purple, the procession, the incense, the choir,
the organ – a frontal attack on all senses.
On April 14th we
held our annual patients’ forum at St Thomas’.
Organised for the Hughes Syndrome Foundation by Kate Hindle,
this meeting seems to grow year by year.
The afternoon was
devoted to short talks, followed by the ever-popular questions
and answers section. There were 120 patients and friends registered.
Munther Khamashta,
my colleague who runs the lupus pregnancy clinic (technically
mainly the APS pregnancy clinic) gave an update on treatment,
highlighting the improvements in management achieved with
early diagnsosis and more pro-active treatment, both medically
and obstetrically, for example with close monitoring of the
in-utero foetus’ blood flow by sensitive Doppler imaging.
Two patients gave
superb talks on their own stories, Mary McDonald on the long
and often tortuous road to diagnosis which resulted in the
publication of a paper: Patients’ experience of a diagnosis
of Hughes Syndrome, and Yvonne Wren on her experience with
INR self-testing on warfarin. Professor Beverley Hunt, Eve
Knight of Anticoagulation Europe
and Joanna Coleman of Roche Diagnostics covered aspects of
treatment, again highlighting the common sense of INR self-testing,
especially when warfarin control is erratic and also discussed
the future of warfarin. Sophia Georgopoulou, who has recently
completed a degree study on the role of social support in
Hughes Syndrome, presented the findings from her MSc dissertation.
Patient
of the month
Mrs CL, aged 51,
was diagnosed as having Hughes Syndrome, with a long history
of headaches, two previous miscarriages, and recently, worrying
memory loss. She had moderately strong levels of anticardiolipin
antibodies.
A brain scan was
normal apart from two small ‘dots’ – commonly
seen at this age, and usually regarded as ‘within normal
limits’.
She was ultimately
treated with warfarin, with definite improvement in balance,
and in memory (she was a keen Sudoku player and once more
was up to speed).
Her warfarin control
was managed by her local anticoagulation clinic, but the INR
did fluctuate. One weekend (of course it was a three day holiday
weekend), she developed increasingly severe migraine-like
headaches. She called the local hospital who advised her to
come to casualty. Her GP had previously provided Mrs CL with
two ampoules of low molecular weight heparin for such an event,
so Mrs CL opted to self-inject. There was immediate improvement
(almost total) of the headache. She did then queue up at her
local casualty, where the INR was found to have fallen to
two.
What is
this patient teaching us?
Possibly a number
of lessons. In an ideal world all patients with Hughes Syndrome
would be able to self-test – if for no other reason
than to avoid a stroke. Of course, this is not universally
practical – and there are obvious safety and responsibility
issues to consider.
However, where
a Hughes Syndrome patient on warfarin does develop worrying
features, and INR testing is not close at hand, we have found
than an injection of heparin (it must be the low molecular
weight variety) is safe, and often an effective short-term
measure prior to re-aligning the warfarin dose. Obviously,
this could only be under the guidance of the patient’s
doctor.
The other ‘lesson’
concerns the two ‘dots’ on the MRI brain scan.
A few years ago, these would have been regarded as a badge
of ageing. However, a very important study was published by
an x-ray team in Holland (first author Vemeer!) who retrospectively
analysed decades of brain MRIs, and showed that the presence
of these ‘mini-clots’ could in fact presage the
development of more significant lesions over time. Vital observations
for patients with Hughes Syndrome and the fight against stroke.
April
2010
A dry month. Very
odd for April! The month when the Icelandic volcano closed
the skies of Britain – more of that later.
There were two
meetings in April, one in Birmingham, UK and the other in
Galveston, Texas, US.
The meeting in
Galveston was big – the thirteenth International Congress
on Antiphospholipid Antibodies, organised by Silvia Pierangeli.
The meeting has
grown and grown in the past 26 years following our first APS
meeting in Hammersmith Hospital, London ( under 40 attendees
in 1984!).
The meeting was
a marvellous workshop, bringing together not only clinicians
and laboratory researchers, but members of patient groups
as well, such as Leslie Cornfeld (New York), Kristina Baily
(Atlanta), and Seresa Crowson who is the President and Founder
of the newly formed American APS Association.
The conference
was opened by Nigel Harris, who had originally worked on the
introduction of the antiphospholipid (aPL) test in my lab
in 1983. Nigel went on to an illustrious career (with Silvia
Pierangeli) in the USA and, more recently, to become Vice
Chancellor of the University of the West Indies.
Attendees came
from many countries and from most of the major APS research
centres – Milan, Barcelona, Sapporo, Chicago, New York,
London, Utrecht, Brescia and Chapel Hill and the majority
of the presentations and posters focussed on the (complex!)
mechanisms by which aPL appear to cause thrombosis. It is
probably fair to say that although the mechanisms are better
understood, they remain something of a mystery (at least to
a simple physician like me!).
Silvia and her
two co-authors Maria Bertolaccini and Munther Khamashta have
helped us by editing a superb ‘Special Issue’
of the Lupus journal, including all the abstracts, as well
as reviews by the leaders in the field - http://lup.sagepub.com/.
The meeting lasted
four days, but I had to beat a retreat before the end –
and here, unexpectedly, came my very lucky break! After an
overnight flight back to London, my flight touched down at
Heathrow at 11.30am – just half an hour before all UK
airports were closed down. Most of the European attendees
were stuck in Galveston for an extra week – a number
of them camping out in the home of Silvia and her husband
Alvaro Schleh.
One colleague whose
work particularly impressed me was Tom Greco. Tom and his
wife, practising in a clinic in Waterbury, Massachusetts have
built up a large clinical practice of patients with Hughes
Syndrome. They are strong believers in the frequency of the
syndrome, and find that many current publications under-estimate
its prevalence. Amongst other publications, they recently
reported on 344 patients with acute coronary syndrome and
found 40% aPL positive in one of more tests (Greco, TP et
al. American Journal of Clinical Pathology 2009, 132, 613-620).
The second meeting
– a one day workshop in Birmingham, brought together
haematologists, lab workers and patients groups involved in
anticoagulation. It was marvellous to see how many patients
(and clinics) were moving towards INR (prothrombin ratio)
self-testing – something which has become almost a religion
of mine. It was particularly encouraging to see the collaboration
between many anticoagulation clinics and those patients also
using their own machines. Until the hoped for newer anticoagulants
come along, I believe INR self-testing (just like the sugar
self-testing in diabetes) has got to be an improvement.
Home by train.
One and a half hours. No airports.
Patient
of the month
This month saw
the return of a patient I last saw fifteen years ago. A young
student aged 23, he developed an acute leg thrombosis (DVT)
following a weekend football match. At first it was thought
to be a calf injury, but the subsequent history and investigations
indicated a DVT.
He was fairly quickly
tested for aPL and found to have a strongly positive result.
Over the next two
years he developed further DVTs, each time following the weaning
off from warfarin. His physicians decided to advise life long
warfarin and he returned to his own country.
Last month, fifteen
years later, he returned for assessment. In the intervening
years, he had obtained a further degree in America, and held
down a busy engineering job in his country. During the past
two years, he had felt ‘unfit’, complaining of
shortness of breath on exercise and occasional (slight) chest
pains.
A review of his
warfarin control data (INR) clearly showed his results had
been less than perfect – indeed very definitely less
than perfect, with the INRs frequently in the 1.5-2.5 range.
Lung tests were fine, but the heart tests, despite showing
good coronaries, demonstrated poor perfusion to the cardiac
muscle.
What is
this patient teaching us?
I believe that
unlike the worldwide recognition of brain and placenta involvement
in Hughes Syndrome, the effects of ‘sticky blood’
on the heart may have been under-recognised. As well as coronary
and valve disease, it is becoming clear that smaller cardiac
blood vessels may well become compromised if the blood supply
is ‘sludgy’.
This case reinforces
the message of recent studies such as those by Tom Greco and
his team: it may be that there is a population of cardiac
patients out there in whom APS – or ‘sticky blood’
– is a cause – a possibly preventable cause.
March
2010
Rain, rain, snow,
cold! So different from last year. This cold grey winter has
gone on for nearly four months. Today, the last day of March,
we were wrapped up in overcoats, umbrellas and scarves. I
really feel sorry for the tourists, scurrying from shop to
shop. What a difference a year makes!
Earlier on this
month I took part in a renal/kidney conference at Hammersmith
Hospital. This was, for me, an excellent one day meeting on
kidney lupus, organised by the Hammersmith Hospital nephrologists,
Liz Lightstone and Megan Griffiths. My job was to review the
effects of the antiphospholipid syndrome on the kidney (not
simply kidney thrombosis, but also kidney artery and vein
occlusion).
For me, it was
a journey back in time. Surprisingly, perhaps, I had not been
back to Hammersmith for 25 years, since I had left for St
Thomas’ Hospital in 1985. It is an example of how time
flies – especially when one is busy. “The Hammersmith”
has changed little – a slightly dingy collection of
buildings snuggled up to the high walls of Wormwood Scrubs
prison.
My memories of
the Hammersmith are still vivid – for it was here that
we described the antiphospholipid syndrome. The ward rounds,
the animated discussions of our cases, the presentation of
our findings to the ‘grand rounds’ – and,
in 1982, the major presentation of the syndrome to the ‘Heberden
Round’ – the annual meeting of the British Society
of Rheumatology.
In particular,
the vivid memories of so many of my research fellows who played
such an active part in the description of the syndrome –
Dr Helen Englert (Australia), Dr Genevieve Derne (Belgium),
Dr Charles Mackworth-Young (London), Dr Bernie Colaco (London),
Dr Mee-Ling Boey (Singapore) and later, Dr Aziz Gharavi (Iran),
Dr Nigel Harris (Jamaica) and Dr Ron Asherson (Cape Town).
And the memory
of the first ‘world’ conference on APS (35 registrants)
held at Hammersmith. And the day on 26th November 1983, when
our Lancet research paper on labs methods for detecting antiphospholipid
antibodies was published – when we are repaired to an
Italian café for lunch in nearby Shepherd’s Bush!
Patient
of the month
Mrs IB (61) was
referred to me by an old friend Pat England, a semi-retired
orthopaedic surgeon. Her history was one of ‘classical’
Hughes Syndrome, with lifelong migraine, one DVT, balance
problems and deteriorating memory. Interestingly, her daughter
also had a history of severe migraine, having had to spend
two to three days each month in the school ‘darkness’
sick room.
Mrs IB’s
past history was otherwise ‘uneventful’ apart
from two years previously having three fractured metatarsal
bones in the foot.
She was tested
for antiphospholipid antibodies and found positive. She was
started on low-dose aspirin (with the possibility of a heparin
trial if aspirin was less than successful).
What is
this patient teaching us?
Look at the last
part of the history: three spontaneous fractures of the toe
bones (metatarsals).
Some years ago,
at St Thomas’ hospital, we noticed a ‘run’
of Hughes Syndrome patients with seemingly spontaneous fractures
of the bones in the feet.
This condition
– widely known as ‘march fracture’ following
its description in some army recruits after long training
marches, was always regarded as a simple stress fracture.
Following our observations
in St Thomas’, we rapidly collected a series of a dozen
or more patients with Hughes Syndrome who had had similar
‘march fractures’. (Dr Sangle, one of our able
research fellows was largely instrumental in following up
on these patients). It seemed more than a coincidence to us,
and suggested that the bones, just like other organs, might
suffer from impaired circulation in Hughes Syndrome.
Since our publication
on this association, a number of similar observations have
appeared including ‘spontaneous’ fractures of
ribs, vertebrae and other bones.
Whilst this complication
of Hughes Syndrome is rare, it does widen the spectrum of
the disease to include orthopaedics.
Until now, the
impact of the syndrome on the speciality of orthopaedics was
largely limited to the (important) matter of pre-operative
blood screening for ‘sticky blood’ prior to knee
or hip surgery.
Now it seems the
ripples are spreading more widely.
February
2010
What a long winter!
For three months it has been wet, cold, windy and …
miserable. Darwin must have had something to say about hibernation.
Three lectures
this month – two GP lectures and one specialist. The
specialist talk was in Barcelona – to their annual ‘Ten
Topics’ meeting (even my one day in Barcelona was cold
and wet). This meeting, voted last year as the most popular
Spanish medical meeting, follows on the success of the London
meeting – but to a larger audience of 300 attendees.
As with the St Thomas’ meeting, the emphasis in Barcelona
is heavily on lupus and Hughes Syndrome, and the level of
both content and discussion is high.
Each year the venue
is the same – the hotel Sants – a large, functional
hotel over the main railway station in Barcelona, well equipped
for meetings and conferences – of many varieties. Unforgettable
was the ‘Ten Topics’ meeting five years ago when
we shared the conference rooms with an annual ‘sex industry’
conference. Wandering around the hotel foyer were two specimens
of attendee – the ‘Ten Topics in Rheumatology’
doctors with their conservative conference bags, and the undoubtedly
more exotic ‘sex industry’ conference delegates
with (one can only presume) their more unorthodox kits!
The two GP meetings
here at London Bridge Hospital were, as always, memorable.
The second meeting held on a Saturday morning (!) attracted
100 GPs. The post-lecture discussion again opened ones eyes
to the importance of our syndrome in general practice –
the migraine, the miscarriages, the memory and balance symptoms,
and even the more severe complications of untreated Hughes
Syndrome – the angina and the strokes.
As always, the
discussion centred around ‘how many cases have we in
our practice?’ and ‘how common is the syndrome
in reality?’ And as always the answer remains uncertain.
It is one of my
ambitions to attempt a realistic survey to try to answer some
of these questions. It is a project which could be fairly
easily carried out, given the funding, say, for a research
graduate.
John Wolffe and
his family have done much to help our charity, and also recently
took part in a BBC Breakfast TV programme about Hughes Syndrome.
I was interviewed and again asked ‘why does the public,
the media and the medical profession know so little about
Hughes Syndrome?’ I sometimes feel that the media would
like specialists such as myself to criticise GPs for their
apparent lack of knowledge of the syndrome. That I would never
do, having been a summer locum GP for nearly fifteen years.
Why, then, the
lack of general knowledge about Hughes Syndrome?
Perhaps, surprisingly, it is not easy to answer. I am reminded
of the same lack of public awareness of lupus back in the
early 1970s when I set up my lupus clinic. At least that has
changed with the weekly lupus diagnosis on the TV programme
‘House’.
New studies
My colleagues at
St Thomas’ are starting a trial of the new anticoagulant
‘dabigatran’ (who thinks of these names?). As
you know, we have waited a long time for a genuinely new drug
that might prove an alternative to heparin or warfarin. This
drug has passed its preliminary hurdles and looks promising.
(The joy of not having to check INRs!). Such studies are painfully
slow, but with the large clinical experience at St Thomas’,
we hope to get an answer.
Two interesting
studies appeared in January. The first, from the lupus pregnancy
clinic at St Thomas’, compared the pregnancy outcome
in antiphospholipid antibody (aPL) positive pregnancies in
women with or without a previous thrombosis. As might be expected,
those with previous thrombosis had a poorer success rate.
On a similar theme
– Hughes Syndrome pregnancy – a group in Singapore
(Mak et al, Rheumatology 2010, 49, 281) found in a survey
of five major trials that a combination of heparin and aspirin
is superior to aspirin alone in pregnancy success rates of
aPL positive women with recurrent pregnancy loss.
Patient
of the month
A 57 year old solicitor
developed visual disturbance, diagnosed as optic neuritis.
He quickly went on to develop weakness in the limbs, balance
problems, and patchy loss of sensation.
He was diagnosed
as having multiple sclerosis. Over the next two to three years
he deteriorated and was largely confined to a wheelchair.
His local physician,
however, didn’t let things rest. Blood tests showed
a high aCL test (very high, in fact, at over 70 units). The
neurologist at first stuck to the MS diagnosis (“positive
aCL tests are sometimes seen in MS”), but the patient
and his physician were dogged and he was referred to our centre.
On examination,
the neurological features of course suggested MS. But there
were two small clues – firstly, the long history of
frequent headaches, and secondly, the borderline low platelet
count (107,000 – corrected to 130,000 on manual checking).
Eventually, it
was decided to start a trial of warfarin treatment. Nothing
to lose perhaps. And for six months, nothing much changed.
At follow ups, the warfarin anticoagulant INR card read 2.1,
2.5, 2.3, 2.6 ….. The dose was increased (the patient
now self-testing) ….. 3.5, 3.7, 3.8, 3.9. And clinical
improvement! For the first time in years, the patient is mobile
and, under physio guidance, is beginning to regain limb strength.
What is
this patient teaching us?
I make no apology
for coming back to MS. Such a difficult diagnosis. And with
the odds stacked against recovery in severe cases. And –
it must be said – with a reluctance in some quarters
to accept that some cases of APS may closely mimic the disease.
In this month’s
patient, time will tell. But for me there are two –
maybe three – lessons.
Firstly, that Hughes
Syndrome, if it starves the brain of oxygen, can mimic almost
any neurological condition. Secondly, that warfarin under-treatment
in some cases of Hughes Syndrome is a waste of time. Rather
like treating an under-active thyroid with half the dose of
thyroxine, or treating diabetes with half the dose of insulin.
Thirdly, the platelets
may be important players in the ‘sticky blood’
syndrome. A low platelet count in the machine used for testing
can sometimes be ‘artificially’ low due to platelet
stickiness. A small clue, perhaps, but good medicine is based
heavily on good detective work.
January 2010
Temperature two
degrees higher than the South Pole! So shouted the newspaper
headlines. More snow and railway chaos! As a nation we are
obsessed with the weather – not surprisingly perhaps.
My thanks (and congratulations) to all the lupus team at London
Bridge Hospital – all of whom came in by train –
and all of whom made it! Every day.
This year, we have
plans for a series of GP seminars on both Hughes Syndrome
and lupus, as well as postgraduate meetings (notably the annual
Ten Topics meeting on 1st and 2nd July).
The national Patients’
Forum is planned for Thursday 13th May at St Thomas’
– for more details do contact Kate at the Hughes Syndrome
Foundation.
Porto
I was one of the
overseas speakers in the annual medical meeting in Portugal
to lecture on Hughes Syndrome.
For me, the visit
was very thought provoking. The reason? – the organisers
had given me a rather unusual topic – ‘non-thrombotic
aspects of the antiphospholipid (Hughes) syndrome which respond
to anticoagulation’.
In other words,
we know that medicine such as aspirin, heparin and warfarin
protect against clots – but could they possibly have
other beneficial effects?
The answer is clearly
a ‘yes’. And in my talk I chose ten illustrative
histories taken from patients I have seen in the London Lupus
Centre at London Bridge Hospital.
Rather than describing
them now, I will discuss ten examples in more detail in later
blogs.
I have listed these
examples partly to demonstrate the variety of clinical faces
of the syndrome. Some have already been described in previous
blogs and in the book Understanding Hughes Syndrome. Others
will be described in this and future monthly blogs.
Patient
of the month
Mrs KT, a 48 year
old housewife had had a long medical history. From the age
of fourteen, she had suffered regular migraines, double vision,
pins and needles (thought at first to be early MS), thyroid
problems and poor memory.
One day in 1999,
she suddenly had a heart attack. Taken into intensive care,
her treatment included twice daily heparin injections and
a daily aspirin.
“To my amazement
I could read. My eyes were totally clear”.
Later that year,
she started to develop angina.
Angiograms showed
clear coronaries.
At this stage one
of the blood tests showed the words ‘lupus anticoagulant
positive’, but no medical checks were made. The angina
continued.
Mrs KT did what
so many now do – she surfed the web and came up with
details of Hughes Syndrome. The rest is history.
What is
this patient teaching us?
Some of you may
already have spotted the clues. The patient KT is Kay Thackray
whose book Sticky Blood Explained is, in my view, the best
book ever written about Hughes Syndrome.
Kay went on to
lifelong warfarin, with a return to a full, and angina-free
life. Her book provides a clear understanding of the complexity
of the syndrome, and what it can mean to have a complicated
disease (which might even have television’s ‘Dr
House’ scratching his head).
One of Mrs KT’s
symptoms was angina, leading to a possible heart attack. It
is easy to see why, amongst all the other clinical problems,
milder cases of angina could be overlooked.
But it is my strong
belief that angina is an important clinical feature –
indeed an under-recognised feature of some cases of Hughes
Syndrome. And a symptom which can be relieved by anticoagulants.
It has often seemed
to me that while neurological (brain) complications of Hughes
Syndrome are becoming better recognised, the heart features
have lagged behind. Hopefully, that is changing.
I predict that
in the next few years, antiphospholipid blood tests (simple
and cheap) will become part of the routine investigation of
any young (eg 50 or less) patient with angina or suspected
heart attack. Potentially so treatable.
December
2009
Snow. Lots of it. Chaos in London – roads unpassable,
trains cancelled, channel tunnel closed – Europe cut
off! This year has bucked the trend – white Christmases
are rare in London which is generally warmer and drier than
the rest of Britain.
This month included, for me, two meetings touching on Hughes
Syndrome.
The first was a one day meeting in Manila (jumbo-jet out,
one day in Manila, jumbo-jet back). A crazy schedule, but
well worth the effort and time. This was the second Asia-Pacific
‘Ten Topics’ meeting.
First held in St Thomas’ some 25 years ago, ‘Ten
Topics in Rheumatology’ – a postgraduate two day
clinical meeting, has grown from strength to strength. Concentrating
as it does on autoimmune conditions such as lupus and Hughes
Syndrome, it bucked the trend of the then rheumatology meetings
by broadening clinical shared experience in these complex
diseases.
With the organisation in the hands of Sandy Hampson (www.tentopics.com)
the concept took hold and now ‘Ten Topics’ are
held regularly in Barcelona, Rome, Argentina, Nice –
and last year in Singapore - the first Asian Ten Topics, organised
by Professor Feng – a father figure of Asian rheumatology.
The meeting in Manila – organised by Sandra Navarra,
was an eye-opener. Two hundred keen trainee doctors, a jam-packed
programme (including a patients’ meeting) and blazing
enthusiasm (both lupus and Hughes Syndrome are big, big problems
in the Philippines): lupus, for example, has overtaken rheumatoid
arthritis in prevalence there.
The second December meeting was held nearer home – in
London Bridge Hospital on 18th December, a week before Christmas.
There was a small (30 strong) ‘think tank’ meeting
organised by the London Lupus Centre to review data on a promising
‘new’ drug – Rituximab. This drug (used
for a number of years for lymphoma) selectively attacks ‘B
cells’ – the cells producing antibodies (such
as antiphospholipid antibodies, the major suspects in Hughes
Syndrome).
This workshop was attended by experts (mainly nephrologists
and rheumatologists) from all the major lupus centres in the
UK. As well as updating the growing experience in lupus (very
promising), some very preliminary data was shared on experience
in Hughes Syndrome, where a reduction in antibody levels and
encouraging clinical responses were seen.
Patient of the month (a short case!)
Mrs MJS, a 41 year old patient, had a strong family history
of Hughes Syndrome, with other family members suffering migraine,
miscarriage, two relatives with multiple sclerosis, and two
with stroke (both testing positive for aPL).
Mrs MJS had, herself, suffered frequent headaches, often with
double vision, balance problems, stomach pains. Rarely a week
went by without some of these symptoms. She had been investigated
and no obvious cause was found. Brain scans were normal.
Egged on by her family, she was tested for antiphospholipid
antibodies and found strongly positive. She was started on
low dose aspirin. The rest, as they say, is history.
Last week I saw Mrs MJS in clinic – the last clinic
before Christmas. For the past year (on aspirin) she has had
no headaches. And no stomach pains. Life has improved beyond
recognition.
What is this patient teaching us?
Perhaps a more appropriate heading might be “why so
many questions”.
Why do some aPL positive patients respond so convincingly
to aspirin – almost miraculously as in this patient?
And in others, no response at all? Why do some people respond
well to heparin and less well to warfarin? Why do some patients
on warfarin respond to an INR of 3 and other need even ‘thinner’
blood – an INR of 3.8 or even higher in some individuals?
Perhaps the answer lies in the complexity of the clotting
process. All medical students struggle with the complicated
flow-chart of the steps involved in clotting. Perhaps in the
not too distant future, haematologists will be able to pinpoint
an individual’s clotting defect much more precisely,
and give us some sort of prediction as to the therapy most
like to succeed.
The future
Christmas is upon us and the new year arrives soon. From the
medical viewpoint two important meetings come up in 2010.
These are the thirteenth international antiphospholipid meeting
– a meeting which attracts many of the world’s
leading researchers – a meeting which also encourages
patient participation (www.utmb.edu/apla2010/).
The other – held every three years – is the international
lupus conference – to be held in Vancouver in July.
For those of us who can’t get to either, the good news
is that abstracts and highlights of both meetings will be
published in the international journal Lupus (www.lup.sagepub.com).
A happy and healthy New Year!
November
2009
The rains finally
came – wet all over the UK, but disastrous in the Lake
District.
We are even more
conscious of the weather as we now we have a lovely new puppy
– Lucy – a jet black Schnauzer – non-stop
walks and play. Earlier this year our old (17 years old) Westie,
Rhys, died. I couldn’t write about it.
The rain was also
a major feature in a visit Monica and I made, in early November,
to give a talk to the patients’ lupus society in Asturias
in northern Spain. The other guest lecturer was Robert Lahita
– lupus doctor from New York, editor of one of the major
lupus textbooks – and old friend.
The Asturias Lupus
Association brings with it a wonderful story. Some years ago,
this small group of (mainly) ladies bought some tickets for
the annual Spanish lottery – a major national event.
They won second prize – 15 million euros! Now
their association has an office, subsidise research posts
and projects, and fund a prestigious annual lupus meeting
– one of the best (and friendliest) it has been my pleasure
to attend.
Britain has a new
American ambassador, Louis Susman, an appointee of President
Barack Obama. Mrs Susman, herself a lupus patient, has been
a major supporter of lupus research in America.
Within a month
of her arrival here in London, and despite an unbelievable
business and social diary, Marjorie Susman made it one her
first objectives to meet a group of people working in lupus.
At a reception
held at the ambassador’s official residence, Mrs Susman
brought together doctors, charity workers and friends working
for lupus and for Hughes Syndrome. What marvellous good fortune
for the UK to have such a positive and energetic supporter
to join us.
Patient
of the month
A 53 year old man
(Mr M J) was diagnosed with multiple sclerosis. He had developed
visual symptoms, balance problems, changes in sensation and
severe headaches. The brain scan showed abnormalities (white
patches) compatible with MS.
His local neurologist
however, felt that there were some odd features. He carried
out more tests and came up with a strongly positive test for
antiphospholipid antibodies (aPL).
After a lot of
discussion between his neurologist and ourselves, it was decided
to start Mr M J on warfarin.
Clinically, there
seemed to be some improvement. The headaches all but disappeared.
The seemingly relentless progression of the ‘MS’
halted. But there are problems. Despite self testing, the
INR still fluctuates; he finds the headaches and balance problems
returning when the INR falls below 3.5. He has also moved
to a new town where his current neurologist doesn’t
believe in the diagnosis.
However, three
years on, the disease remains clinically stable.
What is
this patient teaching us?
‘MS’,
probably like ‘arthritis’, is almost certainly
the end product of a number of processes. In our early studies
of the similarities between MS and Hughes Syndrome, we reported
three observations:
1. A staggering
32% of our patients with positive tests for aPL had, at some
stage in their medical journey, been labelled as ‘possible
MS’.
2. The clinical
pictures of MS and Hughes Syndrome could be tantalisingly
similar.
3. The MRI brain
scans in the two diseases were indistinguishable (read ‘blind’
by consultant neuro-radiologists).
It doesn’t
take much imagination to recognise the implications of these
findings. It is quite possible that some patients out there
with a label of ‘MS’ actually have Hughes Syndrome
– potentially treatable. Is it 1% or 5% or more?
As with the case of Mr M J, it is apparent that neurologists
are divided.
There is urgency
about the need for a really proper, prospective neurological
survey in MS clinics to try to find the true figures. Guesswork
won’t do. Let me keep you posted.
October
2009
What
a scorcher! Today’s paper (October 29th) described the
glorious autumn colours and the ‘flocking to the beach’
as temperatures reached 20 degrees Centrigrade (68 degrees
Fahrenheit). Here in Kent the drought continues – but
this wonderful Indian summer begins to make up for awful July.
October has been a busy month, especially in the clinic where
we are seeing 300 lupus and Hughes Syndrome patients a month.
Those who have visited our clinic at London Bridge will know
how good our secretarial and clerical team here is –
certainly the best I have ever worked with. Led by Sandy Hampson
who, as many of you know, is herself a lupus patient, they
are dedicated, efficient and great fun. My thanks to them.
On the research and education side, our charity, the Hughes
Syndrome Foundation, has been joined by Lynne Kirwin who has
taken on the voluntary role of Chief Executive Officer. Lynne
is a huge asset to our work, coming from a background of media
and marketing, she is a wonderful colleague, full of ideas
and energy. We are now holding monthly meetings to plan next
years fundraising and education activities. If any of you
reading this, or your family and friends, would like to help
in any way, please do contact Kate on 0207 188 8217 –
we would all appreciate it so much.
Our big meeting this month was the annual American College
of Rheumatology meeting – the best of the ‘big’
meetings. David D’Cruz, Shirish Sangle, Rachel Davies
and Laura Bertolaccini (the first Louise Gergel Fellowship
research fellow) all presented research papers there. I didn’t
go, but still hope to discuss highlights gleaned from the
abstracts and from my colleagues in my next blog.
My main presentation this
month coincided with the American meeting – a lecture
to the Italian Society of Nephrology in Rome. A wonderful
one day visit, with many good friends in the audience. Like
all the other organs, the kidney can be involved in Hughes
Syndrome, with lesions ranging from large thromboses to multiple
micro-clots – equally dangerous if not treated. One
of the clinically important findings has been that of localised
narrowing (presumably following localised clotting) of the
kidney artery – a condition which leads to raised blood
pressure – and if spotted and treated, can be cured.
Ideas often come out of the blue. This week, I met a retired
GP from Dublin who had been following my work. He made an
interesting observation which I had never considered. Maybe
one of the reasons a healthy diet helps lower the risk of
clotting in Hughes Syndrome comes from salicylates. Fresh
fruit and vegetables, it seems, contain natural salicylates
(aspirin-like compounds) – ingredients which slowly
disappear with storage. It is possible that even the small
amount of salicylate taken in this way could have a clot-protective
effect.
Patient of the month
A very
‘short’ case this month. A 59 year old lady had
been diagnosed with Hughes Syndrome, having previously suffered
miscarriages, one episode of low platelets, and a TIA (mini
stroke). She was put on to lifelong warfarin.
Of late she had developed discomfort in the right side of
her face, with ‘toothache-like’ pain in the jaws,
and tingling and ‘nerve’ pain in the left cheek
and around the left eye. Initially she was concerned about
whether it was another TIA but was assured that it was not.
Interestingly, she noticed that the face symptoms always worsened
when the warfarin control was poor (ie. when the INR was low).
What is this patient teaching us?
Her condition is known as ‘trigeminal neuralgia’
– a fairly common, but rather unpleasant symptom. The
trigeminal (‘three branches’) nerve supplies the
side of the face – one branch to the forehead, one to
the cheek and the third to the eye.
What this patient has observed is very interesting,
and not something that I have previously written about.
I have always maintained that the organs of the body
most sensitive to ‘sticky blood’ in Hughes Syndrome
are the placenta, in pregnancy, and the brain. Perhaps we
should add to that list the ‘nerves’. A number
of my patients have developed symptoms suggestive of nerve
irritation, for example, in the leg or arm and, in a number,
these unpleasant nerve symptoms improve with anticoagulation.
[Perhaps a parallel situation is seen in diabetes, where the
nerves are very sensitive to trauma or to poor blood supply].
In any event, I think this patient is teaching us a lesson:
nerve symptoms can be prominent in Hughes Syndrome. Perhaps
future research publications will confirm the observation
reported in this blog!
September 2009
‘Barbecue
summer’ it was not. July was terrible, but things have
improved. So much so, that during the whole of September there
were only two rain showers in our town in Kent – the
garden is parched!
I must start on a sad note. Many of you will have read in
the newspapers of the sad death of Lucy Vodden. Lucy, one
of my patients in the Lupus clinic, was a childhood friend
of John Lennon’s son Julian. She was the ‘Lucy’
in John Lennon’s classic song Lucy In The Sky With Diamonds.
Julian had drawn a picture of his little friend Lucy surrounded
by sparkling diamonds – a picture which inspired John
Lennon to write the song. Her sad death has triggered a number
of articles in the Times and other newspapers, and today’s
Mail on Sunday (4th October) has come out with an extremely
well written two page article giving details of lupus and
Hughes Syndrome. The article ends “and sufferers will
always be so grateful to Lucy. She raised the profile of the
disease – not for herself, but simply to help others”.
Hear, hear.
Two lectures this month – one in Copenhagen and one
in Birmingham. By coincidence both meetings had a similar
theme – how to improve our lab tests for lupus and Hughes
Syndrome. Perhaps meetings on this topic are becoming more
frequent – I know that all of us dealing with these
two diseases recognise the importance of trying to minimise
the variation in techniques – and in results –
between different labs. Not only critical in clinical practice,
but also when it comes to publishing research papers.
One such paper which came out this week supported something
which our research team at St Thomas’ have always believed
– that individuals positive for antiphospholipid antibodies
(aPL) may require a second ‘hit’ in order to develop
a blood clot. Examples of these might include long haul flights,
altitude, dehydration, infection and even diet (an excellent
study from India showed that aPL positive individuals in Kuwait
are far more likely to develop a clot than similar individuals
in New Delhi -? Lifestyle differences).
Almost certainly, oestrogen – the basis of the old oral
contraceptive pill is one such catalyst for thrombosis in
susceptible individuals. This week’s Lancet paper from
a group of colleagues in Holland strongly supported this view.
They found that women with positive aPL tests who went on
the oestrogen oral contraceptive pill had an increased risk
of both stroke and heart attack. And not just a ‘slightly’
increased risk – stroke was 200 times more likely and
heart attacks 22 times more likely! Staggering figures. If
confirmed, they make a strong case for health authorities
to consider more widespread testing of aPL.
Patient of the month
I’ve got my life back! Such was the joy of 48 year old
Mrs B.R. of Texas (the second patient this month from the
Lone Star state. Over a ten year period, she had suffered
increasingly from three major symptoms – headaches,
memory loss and general fatigue. She had been investigated
in Texas and found to have fairly normal blood tests and a
normal brain scan. Her physicians had, however, picked up
three clues – firstly, a cold, blotchy circulation,
secondly, severe memory defects on formal testing and thirdly,
dry, gritty eyes. The penny dropped and she was found to have
positive tests for aPL and for Sjogrens Syndrome (see below).
She was started on low dose aspirin, but with little in the
way of improvement. While on a six month family stay in England,
two additional changes were made – a three week trial
of heparin, and the addition of quinine (Plaquenil) –
an important treatment for Sjogrens.
The effect of the short trial of heparin was startling –
the memory defects and word finding problems improved and
the headaches all but disappeared.
Back home in Texas, she was switched to warfarin. She is now
back at work in a law firm, having got her ‘life back’.
What is this patient teaching us?
Two big lessons – firstly the profound effects which
Hughes Syndrome can have on the brain – with migraine
and memory loss being both frequent and severe – and
the unbelievable improvement which treatment can produce.
Secondly, the link with Sjogrens Syndrome. This syndrome (dry
eyes, dry mouth, fatigue and aches and pains) is a ‘cousin’
of lupus – less dangerous perhaps, but often undiagnosed.
Plaquenil (derived from quinine – from the bark of the
Cinchona tree, is a very useful (and safe) medicine, especially
good in reducing the fatigue of Sjogrens*.
I sometimes think of my patients with Hughes Syndrome and
Sjogrens being treated with ‘two trees’ –
aspirin (willow tree) and Plaquenil (Cinchona).
*Further reading:
The Big 3 – Hughes
Syndrome, lupus and Sjogrens - available from the charity
The London Lupus Centre book of Lupus
August
2009
I
was wrong! July must have been a temporary aberration. The
sun returned in August (at least in Kent), and once again
the lawn is parched.
We were lucky.
Our annual holiday in St Margaret’s Bay, was blessed
with fine weather – we even dipped our toes in the sea.
St Margaret’s,
situated at the moment south-easterly tip of England, is the
nearest village to France – during the war it was known
as the “Hell Fire Corner”. For fifteen (maybe
more) years I became the village GP there – a locum
for three weeks each summer for the regular GP, the much-loved
Dr Melhuish. Even after becoming consultant at the Hammersmith
hospital, I carried on with our ‘summer holiday locum’
for a few years. Now the rules have changed, but the experience
(and enjoyment) gained was incredible.
Hughes
Syndrome Foundation
Kate and her team
have been joined, as you know, by Lynne Kirwin who is proving
a wonderful supporter of our charity. Lynne has a working
lifetime’s experience in the media, especially in the
world of entertainment and stage, working alongside Sir Peter
Hall, Cameron Mackintosh and the National Theatre.
One of the aims
of our charity is to raise awareness, both in the public and
in the medical profession, and Lynne is already beavering
away at this, and re-asking the important questions –
how common is Hughes Syndrome – does it affect 1 in
100 or 1 in 500 of the population? How common is migraine?
How important is it as a cause of stroke, heart attack, of
‘Alzheimer’s’, of atypical ‘MS’
… for example. I really do believe that we can get nearer
to answers to some of these questions with the help of our
charity and its members. We are now planning more patients’
meetings and questionnaires and I will keep you posted.
Patients often
ask me – why isn’t it more widely known about?
This week’s patients include two common stories –
a patient from Somerset with Hughes Syndrome, severe migraine,
headaches and one small stroke on brain scan. An urgent case
needing anticoagulants, but her GP was sceptical about the
condition. Direct phone call, mailed literature and gentle
diplomacy needed. The other patient all the way from Austin,
Texas – similar story.
Getting the message
across is not for want of trying. All of us in this area of
medicine spend much of our spare time giving talks, writing
articles etc.
In some ways, I
get encouragement from the world of lupus. In 1990 when I
set up the first lupus clinic in the UK, few had heard of
the disease. Now, thanks to the work of Cheryl Marcus and
all who followed her in Lupus UK, most Brits have at least
heard of the disease.
Patient
of the Month
Mrs L.S. aged 51,
was referred to me by Dr Peter Savundra, an outstanding London
ear, nose and throat specialist. She had started to experience
dizzy attacks, culminating in a severe episode of vertigo.
Menieres Disease possibly – but Peter was suspicious.
She had previously suffered increasing headaches of some aches
and pains. A brain scan (MRI) showed one isolated brain lesion
– a small stroke. She tested positive for antiphospholipid
antibodies and he referred her to me.
On examination,
she had two of the tell-tale signs – blotchy circulation
(livedo) and bone-dry eyes on careful tear-testing. Significantly,
some 30 years before, she had suffered a number of miscarriages
but had also had one successful pregnancy.
What is
this patient teaching us?
She had Hughes
Syndrome both on clinical grounds and on blood tests.
The dry eyes and
aches and pains suggested that she also had Sjogrens Syndrome
– a condition which frequently accompanies Hughes Syndrome.
Perhaps there are
two main lessons here. Firstly, that giddiness, balance disorder
and even some cases of Menieres Disease may be features of
Hughes Syndrome, possibly secondary to the effect of ‘sticky
blood’ on the balance organs. I think it is no coincidence
that Peter Savundra is sending me a steady stream of similar
cases.
The second lesson
(or question) relates to this lady’s history of repeated
miscarriage, 30 years before. At the time of writing (31st
August 2009), we still not really know what the long term
(untreated) future for these women is.
I hope that the
stimulus provided by Kate and Lynne, and our charity, will
encourage clinics around the world to try to answer this and
other related questions.
July
2009
When we were younger
autumn started in September. Then it became August. This year
it arrived in July – cold, rainy, early evening darkness.
Apart from the first three days, that is. On Thursday and
Friday the 2nd and 3rd July, we had our annual medical meeting
‘Ten Topics’ at St Thomas’ hospital. Two
hundred registrants, temperatures in the 90s and, yes –
you’ve guessed it – the air conditioning not working.

Ten Topics has
been running at St Thomas’ for over twenty years. It
is a two day postgraduate meeting attracting doctors from
all over the world (nine countries represented at this year’s
meeting). Although the ‘topics’ cover all of rheumatology,
the emphasis has always been on lupus and Hughes Syndrome
and this year was no exception – I’ll highlight
some of the messages from this year’s meeting.
David D’Cruz
(St Thomas’) reviewed the evidence for treatment of
severe lupus and severe Hughes Syndrome with the new ‘biologics’
such as Rituximab. This drug, an agent which attacks the blood’s
“B cells” (the cells which produce the antibodies)
is now being used around the world in cases of severe lupus.
It is very promising – especially in kidney disease
(lupus nephritis). It dramatically cuts the numbers of circulating
B cells and, as a result, reduces the level of many of the
circulating antibodies in lupus. In Hughes Syndrome, the drug
can certainly reduce the level of antiphospholipid antibodies.
However, the results, so far, concerning the associated risk
of thrombosis are not clear cut. These are early days, but
there are two grounds for optimism. Firstly, the drug has
a very good safety record, with a low incidence of side effects.
Secondly, the results in lupus, which has some similarities
to Hughes Syndrome (autoimmune, with antibodies involved),
are very encouraging.
Dr Munther Khamashta
(St Thomas’) reviewed the world literature on ‘catastrophic
APS’. Fortunately very rare, this is a condition in
which widespread clotting suddenly occurs, with life-threatening
collapse of multiple organs. No one knows what triggers this
acute event – two suspects are the sudden stopping of
warfarin (in one or two patients) or an acute infection. The
most successful treatments so far have included full anticoagulation
and, interestingly, plasma exchange.
Professor Angela
Vincent (Oxford) reviewed the topic of other antibodies, recently
discovered, which can affect nerve and brain function –
a topic I touched on in an earlier blog.
One of the main
features of Hughes Syndrome is the prominence of ‘brain’
features – migraine, memory loss, balance problems and
stroke. Another way in which the brain reacts to impaired
blood flow is with ‘movement disorders’. Dr M
Sharif, Consultant Neurologist, reviewed the wide variety
of these which he has seen in Hughes Syndrome – ranging
from simple jerks or tics, through to St Vitus Dance. Interestingly,
so many of these movement disorders go away when proper anticoagulation
treatment is started.
We then had a series
of short talks – ‘hot topics’ – presented
by some of the St Thomas’ Lupus team – Dr Laura
Bertolaccini on ‘progenitor cells’ – some
of the cells which can develop into different tissues; Dr
Maria Cuadrado on ‘proteonomics’ the genetic fingerprinting
of some of the proteins thought to be key players in Hughes
Syndrome. Dr Shirish Sangle presented his work on the clinical
observation that some patients with the syndrome develop localised
artery narrowing. In the arteries supplying the intestines,
for example, this can lead to abdominal pain after a big meal.
Because of the importance of the arteries (both in lupus and
in Hughes Syndrome), ways of measuring the thickness and the
blood flow in arteries is very important. Dr Rachel Davies
highlighted some of the newer sensitive scanning methods in
use.
Two of our overseas
speakers came from neighbouring but very different countries
– Israel and Lebanon. Dr Uthman reviewed his experience
(a big experience) of Hughes Syndrome in Lebanon. Our last
overseas speaker was Professor Yehuda Shoenfeld from Tel Aviv.
He gave a brilliant overview of the autoimmune diseases, reviewing
the evidence that in many cases, infection (eg. virus infection)
might be the trigger. He also presented data on a ‘new’
clinical finding – the acute loss of sense of smell
in some patients with neurological disease – including,
I believe, occasional patients with Hughes Syndrome. A rare
manifestation, perhaps, but it brings me to my ‘patient
of the month’.
Patient
of the Month
Mrs P.E. aged 48,
had two medical problems, Hughes Syndrome and back pain. The
back pain probably dated from a bad fall many years previously,
but recently had become more of a problem. Xrays showed clear
disc disease. The pain had begun to affect the nerves down
the legs – so much so that Mrs E had to regularly stop
after walking 100 yards or so. An MRI confirmed that the narrowing
caused by the discs was compressing the nerves – a condition
known as spinal stenosis.
Mrs E’s Hughes
Syndrome included many years’ migraine headaches, balance
problems and a slightly ‘cold’ circulation. She
had been taking baby aspirin with some success. However, in
2007, she developed a probable DVT (thrombosis) in the arm
and was started first on heparin, then on warfarin.
And the leg pains
disappeared! …… Since that time she has remained
leg pain free – except when the INR falls below 2.5!
- an observation she has made a number of times.
What is
this patient teaching us?
Next year I face
an interesting challenge. I have been asked to give a lecture
at the world conference of ‘rarer manifestations of
Hughes Syndrome’. The difficulty of course is to decide
whether a ‘rare’ manifestation is a part of the
syndrome or is merely a coincidence.
What about our
‘patient of the month’: Hughes Syndrome and back
pain from spinal stenosis? Well …
Firstly, the observation
is clear-cut. Mrs E is a good and careful witness. The back
(nerve) pain improved predictably with good anticoagulation.
Could it be that her ‘sticky blood’ further compromised
her leg nerve pain? Possibly. It is certainly not uncommon
to see ‘nerve’ symptoms such as pins and needles
improve in our patients on starting warfarin or heparin. In
fact, Mrs E is my third patient with Hughes Syndrome whose
‘spinal stenosis’ symptoms have improved with
blood thinning. Three cases might just be a series!
Perhaps the take-home
message is that it is possible to have more than one condition
– and that the one can be influenced by the other. A
‘two-hit’ phenomenon.
June
2009
“Hotter than Barbados”.
The headline in today’s (30th June) daily paper. Wimbledon
sizzling, our garden parched and London decked for summer.
The river boats plying back and forth past the London Bridge
hospital tightly packed with tourists.
Tomorrow we start
our annual international medical meeting “Ten Topics”
at St Thomas’. This popular postgraduate meeting, focussing
heavily on lupus and Hughes Syndrome, attracts doctors from
all over Europe. The speakers are the ‘crème
de la crème’. As organiser, it’s not the
speakers I worry about, but whether the air conditioning is
working. I will let you know.
Last week, I was
invited to an art exhibition run by Jane Phillips, one of
my patients. Her pictures – many of South East France,
were wonderful. Jane was generously giving a donation from
her sales to the Hughes Syndrome Foundation.
Also last week
(again with the temperature in the high 80s), Kate introduced
me to Trevor Glover who is kindly going to help update our
website and make it more attractive and ‘modern’.
June also saw a
reunion. Monica and I had supper with a long lost friend,
David Allison and his wife Deirdre. David was a contemporary
of mine in my early days as a consultant at the Hammersmith.
As a consultant radiologist, he was Europe’s leader
in ‘interventional radiology’ – a genius
who could, with his various probes, reach almost any part
of the body without having to resort to surgery (we used to
call him DynoRod!). Patients with internal bleeding, or with
inaccessible cancers were referred to David from all over
the world. Professor Allison was also a fantastic raconteur
and an encyclopaedia of jokes and stories – it comes
as no surprise to hear that since retirement, David Allison
has become a very successful children’s author.
Patient
of the month
Peter, a 56 year
old man, was referred as possibly suffering from Hughes Syndrome.
His history was fairly typical – with migraine headache,
memory loss and fatigue, though his own doctor was not convinced.
He was accompanied by his sister, Ruth, who having worked
in the NHS (as an EEG technician), helped with the history.
And what a story there was to unfold!
The ‘family
history’ included mum (who had strokes and temporal
lobe epilepsy) and Peter’s three sisters: Ruth (severe
migraine, balance disturbances, swollen parotid glands and
dry eyes); Lesley (multiple miscarriage, severe migraine,
thyroid problems) who died in America of pulmonary embolism;
and Jane (miscarriages, migraines, possible ‘MS’,
and an eye clot) who had been investigated in South Africa
and found to have very positive anticardiolipin antibodies.
Lesley had two daughters – one with migraine and a positive
antiphospholipid (aPL) test and Jane, in South Africa, had
a daughter of 19, who was investigated for migraine and also
found to be aPL positive.
But possibly the
most interesting anecdote came from Ruth. Twenty years earlier
as a fledgling EEG technician, she had practiced on her three
siblings. All had temporal lobe epilepsy – a frequently
‘silent’ abnormality of brain waves.
What is this
patient teaching us?
Many lessons –
the importance of the family history, the prominence of migraine
and the importance of brain symptoms such as balance problems
and ‘MS’. And, of course, the history of multiple
miscarriage.
Intriguingly, the
findings of a form of seizure disorder in the family - long
before the diagnosis of Hughes Syndrome was made, suggests
a link with the condition. Needless to say, my colleagues
at St Thomas’ are now chasing this observation up.
Lastly, a lesson
for the researchers: genetic studies are bound to come up
with data on Hughes Syndrome. But for the data to be truly
meaningful, the input from the clinicians has to be really
comprehensive – often with single patients supplying
many, many clues.
May
2009
May is going out in glorious sunshine. Temperature
here in the mid eighties and a blue, blue sky. A busy month
at the London Lupus Centre, and a lot to report. Today, my
aunt Pat phoned from Liverpool, up in arms because she had
heard that a doctor on the radio had pronounced that taking
regular aspirin was bad. He clearly hadn’t heard of
Hughes Syndrome and the vital role junior aspirin is playing
in the lives of many of our patients (as evidenced by this
month’s ‘patient of the month’ (see below).
I am involved with the Florence Nightingale trust
and its work in bringing to life the Florence Nightingale
museum at St Thomas’ hospital. I am reading the new
book on Florence Nightingale written by Mark Bostridge and
am struck once again by the struggles it took to bring in
medical (and social) advances in those days – our own
efforts at spreading our message seem small by comparison.
I have two May meetings to report:
Patients’ Forum 20th May 2009: the twice yearly
patients’ forum was held this time in Governors’
Hall at St Thomas’ Hospital.
Speakers included Professor Beverley Hunt, who answered questions
about treatment, Dr Munther Khamashta, who talked about Hughes
Syndrome and pregnancy, Dr Laura Bertolaccini, recipient of
the Louise Gergel research fellowship, who reviewed her work
on testing for Hughes Syndrome (of which more below). There
was also an important presentation by Leisel Castelloni Roche
(one of the manufacturers of self testing machines). Leisel’s
talk showed us once again that for many, many patients on
warfarin, simple ‘finger prick’ testing of blood
thickness (INR) has improved their quality of life. As one
of my patients put it ‘I am free to travel abroad, and
to go on holiday with new confidence. When a headache comes
on or the ‘fog comes down’ I am able to immediately
check my INR and, if necessary, to make an adjustment to my
dose’.
Two patients gave memorable presentations –
Hazel Edwards a moving story of her strokes, her balance problems,
her memory loss – and the difficult times before the
diagnosis of Hughes Syndrome was made and life returned to
near-normal.
The second patient was Rita Williams, who took part
in a ‘medical consultation’ with me. Her history
brought out many important aspects of Hughes Syndrome –
not least the genetic side – all of her other siblings,
two sisters and one brother having the syndrome!
The meeting ended with the ‘highlight’ –
the questions and answers session between the audience and
the speakers. Munther and I got into a debate (which we have
regularly!) on when to test for Hughes Syndrome in pregnancy
and miscarriages. The ‘official’ view is after
three of more consecutive miscarriages – because, as
there are many other causes of miscarriage, testing after
only one would not be cost-effective. My own view is any miscarriage
is a tragedy – for the sake of a simple (and cheap)
blood test, further miscarriages could be prevented. I’ve
no doubt that we will return to this debate!
My thanks to the speakers, and to Kate Fitzpatrick and her
team of helpers for a hugely successful meeting. We will keep
you posted on dates for future meetings.
Mainz
The other meeting (a one day meeting in Mainz, Germany)
was very technical, but in many ways equally important. It
concerned the tests for Hughes Syndrome. In the 25 years since
our paper in the Lancet described the assay for antiphospholipid
antibodies (aPL) – the standard blood test for Hughes
Syndrome – things have moved on. There are now dozens
of variations of the original test, and the makers of testing
kits compete with each other. Not surprisingly, the kits and
the results, can differ. This can lead to confusion, for example,
if a patient tests positive in Plymouth and then negative
in London.
This is one of the most important problems facing
us. Fortunately, there is very active research going to try
to standardise testing. This is truly internationally collaborative
work. For example, the St Thomas’ team is working together
with colleagues in Milan, Brazil, Barcelona, Sapporo and the
USA, sending samples to each other and sharing ideas and results.
The one day meeting in Germany was a reflection of
this, bringing together doctors and technicians from clinics
and labs throughout Europe. I genuinely believe that we will
see a gradual smoothing out of our different lab methods and
their occasionally variable results.
Patient of the month
Last week, Galena P, a 26 year old Greek student
came down from Loughborough for a follow-up visit. She was
accompanied by her mother, her aunt and her two sisters and,
for some time, the consulting room was alive with talk, with
laughter, and with inter-family discussion (and disagreements)
all in Greek! It was a happy occasion, because hers was a
success story.
Several years previously, at the age of 19, Galena
had suffered headaches, and two severe episodes of acute ‘Menieres’
– imbalance attacks. She also developed problems with
focussing, and some weakness in the limbs. A brain MRI showed
two small ‘dots’. A diagnosis of probable multiple
sclerosis was made. But there were some other features –
prominent ‘livedo’ (blotchy skin), a strong family
history of autoimmune disease – thyroid problems, in
particular. Furthermore, the illness seemed to have been precipitated
by the oestrogen (oral contraceptive) pill.
She was seen by an old friend of mine, Dr Phaedon
Kaklanonis (Athens) – an astute physician – who
tested Galena for antiphospholipid antibodies (aPL): strongly
positive. He started her on 75 mg aspirin daily and asked
me to see her in London – she was hoping to study in
the UK. That was some six years ago.
This May, Galena returned – completely well.
No sign of multiple sclerosis. About to get married and planning
pregnancies. Still aPL positive, still on junior aspirin.
What is this patient teaching us?
Think of the diagnosis! A simple blood test can change
lives. With hindsight it seems likely that the ‘pill’
triggered brain clotting problems in a girl with positive
aPL antibodies (and with a positive family history of autoimmune
disease).
A presentation mimicking multiple sclerosis is not
uncommon in my experience. Interestingly, so is acute balance
disorder, often initially diagnosed as ‘Menieres Disease’.
This young woman will certainly be advised to continue
her low dose aspirin in pregnancy. However, the unknown factor
is whether, in this patient, aspirin is enough. All our evidence
suggests that warfarin is aspirin better at protecting against
further strokes in those patients showing clinical or MRI
scan evidence of previous stroke. Both Galena and her physician
preferred aspirin alone. So far, they are correct. Nevertheless,
the choice of long term treatment for those patients with
brain clotting remains one of the big questions in Hughes
Syndrome. Not yet fully resolved.
Last night Monica and I attended a musical talent
competition in London. The ‘Voice of Tomorrow’
was a three day extravaganza, the finals of a singing (musicals)
competition, held at a packed West End theatre. Nick Murdoch,
the producer of the show had generously chosen to donate a
portion of the show’s profits to the Hughes Syndrome
Foundation. The evening was great fun and the voices marvellous
(the audience had to vote ‘X-factor style’ for
the winner). The downside was that I had to go on stage to
give a vote of thanks. I am quite happy to give lectures to
medical audiences of a thousand or more – but this was
different. Scared stiff.
My thanks to Mags McCormick and Beth Willis who worked so
hard on the charity’s behalf with Nick and his team,
and to Kate Fitzpatrick and her helpers – Ann Sumra,
Zoe Dwek-Adams, Christine Preen, Kay and Katie Thackray and
Sandy Hampson for such a fantastic effort.
April
2009
The best April
blossom in living memory. The colours in our corner of Kent
– and I imagine in much of Britain – have been
breathtaking. And London was at her very best for the Obama
visit – wall to wall sunshine.
As I write this,
there are a small number of confirmed cases of ‘Mexican
flu’ in the UK. The news coverage has been comprehensive
– somewhat in contrast to the coverage of the rather
severe viral flu-like illness which hit so many people here
a month or so ago – an acute – very acute –
chest infection, leaving a trail of cough and chest complaints
lasting up to a month. My friend, Dr Richard Leach, consultant
chest physician at St Thomas’, described the infection
as ‘almost as vicious as Legionnaire’s Disease’.
Hughes
Syndrome
In the clinic,
we seem to be busier than ever. The range of clinical pictures
of Hughes Syndrome never ceases to amaze me. While the ‘official’
view of the syndrome is “thrombosis and recurrent miscarriage
loss associated with the presence of antiphospholipid antibodies”,
the clinical spectrum seems far, far wider. I have always
been particularly interested in the ‘brain’ manifestations
– the migraine, the memory problems, the ‘MS’.
And the epilepsy – did you know, for example, that recent
publications have found that up to 1 in 5 cases of ‘idiopathic’
(cause unknown) teenage epilepsy are associated with Hughes
Syndrome.
Last week, one
of my patients, herself an EEG (brain-wave) technician, told
me that she had tested four of her siblings – all had
EEG brain-waves suggestive of temporal lobe epilepsy –
a condition in which the sufferer experiences odd cerebral
episodes such as ‘déjà vu’. I have
always believed that temporal lobe epilepsy is an under-reported
feature of Hughes Syndrome – I’ll come back to
this topic in a future blog – but this month’s
topic is the much better recognised association with recurrent
pregnancy loss.
Patient
of the month
Mrs Lesley H, aged
36, had a tragic history of recurrent pregnancy loss. Unlike
her sister, Deirdre*, whose problem was infertility, Lesley
had no difficulty in getting pregnant – her first pregnancy
was in the year of her marriage, aged 19. her problem was
miscarriage. Over the ensuing ten years she suffered no less
than 12 miscarriages – most of which occurred at around
three months, but two of which were late pregnancy losses
at six and seven months. With hindsight, Lesley did have other
clues to the diagnosis of Hughes Syndrome – a long history
of migraine and of a sister and aunt with thrombosis.
Why wasn’t
the diagnosis made? Don’t know. In fairness, the world
of obstetrics has been one of the first to pick up on the
syndrome – indeed Hughes Syndrome is now recognised
as the commonest treatable cause of recurrent pregnancy loss.
The story does
have a happy ending. The penny dropped and Lesley was tested
for antiphospholipid antibodies (aPL) and found very strongly
positive. In view of her terrible obstetrics history, she
was immediately treated in her next pregnancy with a combination
of aspirin and heparin. Success – she now has three
healthy children.
What is
this patient teaching us?
More and more is
being learnt about the reasons why Hughes Syndrome leads to
pregnancy loss. While the most obvious cause is ‘sticky
blood’ and a clogging up of the placenta, we now recognise
that there are possibly a number of reasons – including
the vital earliest stage in pregnancy – ‘placentation’.
It is not surprising therefore that infertility is also now
a recognised association of the syndrome, leading to the use
of heparin in some IVF clinics.
[Lesley’s
sister, Deirdre*, also has high titres of aPL.]
Glasgow
April 2009 was,
in one respect, a ‘red letter month’ for Hughes
Syndrome. Although I first reported the discovery of the syndrome
to a meeting of the British Society of Rheumatology (BSR)
in 1982 – a year before our first publications in the
Lancet and the British Medical Journal, the subsequent annual
meeting of the BSR, sadly showed little interest in the syndrome.
This year however, all that changed. For the first time in
26 years, the BSR devoted a major session to the syndrome.
The main auditorium in the Glasgow convention centre was packed
and I was so pleased to see this recognition of its importance.
There were four
invited speakers and I will briefly highlight their talks
to provide a brief update on what is going on in research
in this disease.
Professor Anisur
Rahman (UCH) introduced the subject. He had first come across
Hughes Syndrome as a trainee doctor in 1990 when is was considered
‘small print’ – no longer so. How do the
antibodies cause thrombosis? Complicated! Imagine the cell
as a ‘sausage’ (be it a blood vessel lining cell,
a circulating cell such as a monocyte, or even a cell-like
particle called a platelet). To get into the cell and cause
the disruption and the clotting, the antibody must penetrate
the ‘sausage skin’ or cell membrane. We now recognise
that this process involves several steps:
1. The antibody
attaches to a protein
2. The antibody-protein warship attaches to a protein on the
cell surface (one group of ‘reception’ proteins
is know as ‘toll-like’ receptors).
3. They enter the cell, and start a cascade of chemical changes
in the cell, leading to inflammation, and to increased ‘stickiness’
of the cells – and in our syndrome – to thrombosis.
What is the relevance
of all this detailed protein chemistry? Well, the hope is
that by identifying target proteins, we will be able to produce
specific antidotes – ‘magic bullets’ –
much like some of the new anti-cancer drugs and anti-TNF drugs
now used in rheumatoid arthritis.
Professor Sylvia
Pierangeli (Texas) one of the world’s leading researchers
in Hughes Syndrome, talked about her detailed work on the
mechanisms of thrombosis. She had studied the disease in mice
– a breed of which developed thrombosis and multiple
fetal losses in pregnancy. So much has been learnt from the
‘mouse model’ – including trials of new
therapeutic agents. Sylvia was careful, however, to remind
us that although there are useful lessons to be learnt from
the mouse, it would be wrong to over-interpret.
It was great to
see Sylvia coming over to the UK as an invited speaker. She
had joined my two research fellow Dr Nigel Harris and the
late (and great) Aziz Gharavi when they moved to the USA and
now runs an internationally renowned lab in Galveston, Texas.
The third speaker
was Professor Lesley Regan. Lesley is not only head of St
Mary’s famous recurrent miscarriage clinic, but also
a TV star with her own weekly consumer’s programme –
Professor Lesley Regan’s Medicine Cabinet.
Professor Regan
gave a clear overview of the many pregnancy problems associated
with Hughes Syndrome – not only the recurrent miscarriage
and late pregnancy loss, but the increased risk of intra-uterine
growth retardation.
Recognition of
the syndrome, and its treatment, has been one of the major
advances in the field of obstetrics in the late 20th century
– the pregnancy success rate in Hughes Syndrome has
improved from a terrible 15-18% in the late 1980s to a present
90% in specialist clinics such as St Mary’s and St Thomas’.
Dr Munther Khamashta
(St Thomas’ Hospital) ended the symposium with a talk
on ‘controversies in APS’. There is no-one better
than my colleague Munther to take on this task. He throws
everything into his work and his views on what’s going
on in our little world. His main topic was the debate over
the detection and treatment of stroke in Hughes Syndrome.
Unfortunately,
some years ago, a large American stroke study came to the
conclusion that testing for APS was not warranted! This study
had a number of major ‘design faults’ which Munther
pointed out. But unfortunately, at least for now, some neurologists
quote this study as evidence against routine blood testing.
We know this is wrong but time – and many more studies
– will tell.
Conclusions
I am optimistic
that, year on year, knowledge of Hughes Syndrome, and its
implications in so many branches of medicine, will improve.
This month, the
British Society of Rheumatology took the syndrome on board.
For us, one of
the successes of this meeting was a meeting with Professor
Lesley Regan at which we set up a joint collaborative study.
This month’s ‘patient of the month’ had
a tragic pregnancy history, but with a happy ending. But what
of her future? Our collaborative study linking one of the
UK’s biggest miscarriage clinics with the St Thomas’
Lupus Unit and its weekly ‘lupus pregnancy’ clinic
may go some way to answering that question.
March
2009
Two important
anniversaries in March – our 43rd wedding anniversary
and our old dog’s 17th birthday.
Our elderly Westie
still gives us as much pleasure in his dotage as he and his
“naughty little sister” did 17 years ago. I’m
sure other dog owners can sympathise, but the dog is the main
reason for our preference to ‘stay at home’.
Lectures
Even professional
lectures, both at home and abroad are planned to allow the
least possible time away (airlines permitting). For example,
I have just returned from a 24 hour round trip to a meeting
in Bergamo, Italy (of more anon).
Of course, everyone
in research enjoys these meetings – not just the new
places, but the friends, and the exchange of ideas. There
are some downsides – airport lounges, for example.
On the other hand,
there can be unexpected – totally unexpected –
pluses. Like the lecture I gave some years ago in Athens.
After my late afternoon talk, my host came up to me and whispered:
“the rest of the day is in Greek. So we have a choice.
I can either take you on a tour of Athens churches and monuments
or, alternatively, I have two tickets for Liverpool versus
Parathanaikos” … magic!
The Brain
The Bergamo meeting
was very interesting. A whole day devoted to antibodies and
the brain. A full house of some 300 Italian neurologists (mostly
young) interested in the causes of brain problems in autoimmune
diseases such as lupus, Hughes Syndrome and MS. Such an important
topic. Do antibodies – such as the antiphospholipid
antibodies found in Hughes Syndrome and some of those found
in lupus and other neurological diseases – have a direct
action on some brain cells? The answer is yes! Huge, obvious
implications for treatment. Two of the overseas speakers were
Vanda Lennon (Mayo Clinic) and Angela Vincent (Oxford) –
both international experts in this area.
Accompanying me
to this one day meeting was Dr Giovanni Sanna, recently appointed
consultant to the Lupus Unit at St Thomas’ Giovanni
has also made the ‘brain’ aspects of lupus and
Hughes Syndrome his own special interest. Both of us came
away buzzing with ideas for new angles of research as well
as plans for collaborative projects.
My own talk was
on Hughes Syndrome and the brain, but with particular emphasis
on stroke … which leads me to my ‘Case of the
Month’.
Patient
of the Month
A 39 year old office
salesman complained of increasing headaches. These had been
present on and off for over a decade and were only partially
helped by paracetamol. Following a suspected (but not proven)
leg thrombosis which followed a knock on the leg during a
football match, he was investigated and found to have positive
anticardiolipin tests. In fact, the reason he was tested was
more to do with pressure from his sister, a known Hughes patients
herself.
He was treated
with a 3 month course of warfarin, and later switched to aspirin.
Although he felt
the ‘baby’ aspirin reduced the frequency of the
headaches, he gradually missed out on, then ceased, the medication.
Eight years after
the leg incident, the headaches became more frequent, sometimes
migranous. Clinical examination was unrevealing and a brain
scan was normal.
One day, while
driving to a meeting, he felt an acute head pain. He felt
mentally “unreal” and, fortunately, pulled into
a lay-by. He must have lost consciousness for some two hours,
later he came to, in hospital, having been found by a passing
police car. He had left sided arm and leg weakness and had
difficulty in speaking. A new MRI scan showed an area of poor
blood supply - a stroke.
In view of this
known diagnosis of Hughes Syndrome, he was fairly quickly
started on anticoagulants.
He has made a full
(if slow) recovery and is now on lifelong warfarin.
What is
this patient teaching us?
All the evidence
over the past 25 years suggests that if untreated, Hughes
Syndrome, can be a cause of stroke – indeed an excellent
study from Rome suggested that of all strokes in the under
45s, Hughes Syndrome underlies no less than 1 in 5.
And yet there seems
to be a reluctance to accept that this is a real risk and
a preventable problem.
Hughes
Syndrome and Stroke
The British government
is now embarked on an excellent stroke initiative, spearheaded
by Liam Donaldson. Many of you will have seen the punchy TV
adverts, advising how to spot the early signs of stroke.
Our charity contacted
the government but (to-date) received a disappointing reply
– their medical advisor (whoever he/she is) did not
feel that there was enough evidence to warrant blood testing
– even in strokes in the under 45 year olds.
It is estimated
that the costs of stroke in financial terms is $43 billion
per annum in the USA and £2.8 billion per annum in the
UK. And that is only the financial cost! Watch this space
…
Lupus and
Rheumatology at London Bridge Hospital
As some of you
know, since my ‘official’ retirement after 40
years in the NHS, I have set up a ‘new’ venture
at London Bridge Hospital, ‘The London Lupus Centre’,
with a number of my colleagues. We have our own four room
department in St Olaf House, London Bridge – ideally
situated as part of the busy London Bridge Hospital, overlooking
the Thames, and across the road from London Bridge station.
We have nine consultants, all of whom trained in the Lupus
Units at St Thomas’, seeing patients with lupus, but
also, critically, patients with ‘general’ rheumatology
problems.
This month we are
setting out on a new venture at London Bridge Hospital –
the ‘London Rheumatology Centre’ – a 24
hour screening service which covers referrals from every corner
of rheumatology, from knee pain to back pain, from osteoporosis
to tennis elbow. We believe that our unique team of nine rheumatologists,
27 orthopaedic surgeons, our x-ray and MRI facilities will
provide a fairly comprehensive back-up service for anyone
wishing to undergo a rheumatology/orthopaedic/sports medicine
‘MOT test’.
It’s a new
service – I do hope it works – there’s certainly
a need for such an available, ‘no frills’, ‘no
waiting list’ service of this sort.
After the bureaucracy
of the NHS, the London Bridge clinic is pure bliss. Just ‘doctor,
patient and secretary’. Immediate appointments. No lost
notes; results within 1-2 days! No committees, no ‘targets’,
no ‘issues’. No armies of managers. And as everyone
who has visited the clinic finds, a marvellous, professional
team of Sandy Hampson, Alison Ward, Kim Hough, Brenda Friedner,
Melody Stritter and Sharon D’Mello.
Of course it is
a private clinic since I am retired from the NHS. But I hope
to include in our program new public/private initiatives,
and a series of patients’ meetings – to host question
and answer sessions on some of the conditions we see.
We have already
held the first. Kate Fitzpatrick will keep you posted via
the HSF website and newsletter on future plans. We hope to
see you there.
February
2009
Leon, Mexico
Leon is a long
way away, especially for a stay of only two days. Eleven hours
to Mexico City, two hours wait, one hour local flight to Leon.
This was to give
the visiting lecture at the Annual Conference of the Mexico
Rheumatology Society. Having agreed over a year earlier to
give the lecture, there was no excuse for complaining about
jet lag when the diary date came up (Friday 13th(!), February
2009).
Yet there in the
meeting, all the travel weariness evaporated. The ‘keynote’
speech was on Hughes Syndrome, and over one thousand keen
young doctors in the audience showed their appreciation and
interest, with a question and answer session that went well
over the allocated time.
Mexico, like Spain,
Italy, Israel, the USA and France, has had a major clinical
and research interest in the antiphospholipid syndrome. The
late Donato Alarcon-Segovia was one of the first to follow
up on our description of the syndrome in the 1980’s,
and two of his trainees, Marie-Carmen Amigo and Antonio Cabral
(this year’s President of the Mexican Rheumatism Association)
have become leaders in the field.
Meetings such as
this give one a renewed sense of optimism that recognition
of the syndrome, of its clinical importance, is indeed gaining
ground. As so often happens, the post lecture coffee break
is where some of the more retiring members of the audience
do their button-holing. And always, amongst the questions,
the personal case …..
One of the rheumatologists
came up to me after my talk to ask about her sister. The sister,
a patient with Hughes Syndrome, had had numerous vein thrombosis,
several strokes, worsening heart valve disease and a major
lung thrombosis. Yes, she was on anticoagulants and had also
been on steroids. They had even tried the new “wonder
drug” Rituximab but this had produced an almost fatal
anaphylactic reaction ……… very humbling.
Of course, another
bonus of a meeting such as this is the reunion with old friends.
The other overseas lecturer was Yehuda Shoenfeld (Tel Aviv).
In the transfer lounge at Mexico City, each waiting for his
long flight home, we had the rare chance of two hours uninterrupted
“shop talk”. Yehuda agreed to edit a Special Issue
on “Immunisation and Vaccination – the good and
the bad” for the journal LUPUS. A true bonus.
Patient
of the Month
Much of my learning
comes from patients. In the book “Hughes Syndrome –
50 clinical cases” (Springer), I have written about
the lessons learnt from 50 of my patients. In my (I hope)
monthly “blog”, I will try to continue the theme.
Mrs J.S., a 52
year old housewife, complained of fatigue, headaches and worrying
memory loss. The fatigue was so bad that she would often have
to get a couple of hours sleep in the late afternoon. Her
GP had examined her and no firm diagnosis was made. The headaches
became more frequent and she was referred to a neurologist.
A brain scan showed 3 or 4 small ‘dots’ but no
tumour or other pathology. She had a past history of three
miscarriages, of teenage migraine and of one possible DVT
(deep vein thrombosis) in the leg.
Her family history
was interesting, one sister having lupus, and mother and an
aunt with underactive thyroid. Two cousins had multiple sclerosis.Examination
revealed one important clue – a blotchy skin appearance
known as “livedo” (or “corned beef skin”,
as one of my patients calls it). In view of the history (as
well as the family history) she was tested for both lupus
and Hughes Syndrome. All tests negative. What to do?
Despite the negative
tests, there was a lot to suggest Hughes Syndrome. She was
started on baby aspirin and quinine (Plaquenil) – a
safe and useful drug used especially in lupus for treating
fatigue.
Within 2 –
3 months there was a marked improvement. However, some 2 years
later, she developed more severe headaches and another possible
DVT. She was started on warfarin and has “never looked
back”. As well as a disappearance of the headaches,
she has noticed a definite and striking improvement in memory.
What is
this patient teaching us?
Lesson 1:
We are sure that out there, there are a number of patients
with Hughes Syndrome yet with negative tests. We have labelled
this group “sero-negative APS” – just as
50 years ago, there were “sero-negative” lupus
cases – simply because the “serum” tests
at the time were not sophisticated enough.
Could this be one
of the reasons? The answer is almost certainly ‘yes’.
And there is some up-to-date news on this. At St Thomas’
we are collaborating with a group in Rome who have developed
a new, more sensitive test for ‘sticky blood’.
And sure enough, of the first batch of samples we sent from
patients with “sero-negative APS”, over half came
up positive.
Lesson 2:
If the clinical suspicion is strong enough, treatment is well
worth a try, despite the negative tests.
Our Charity
It hardly seems
believable that over a quarter of a century has passed since
our description of Hughes Syndrome was first published –
in 3 U.K. medical journals, The British Medical Journal (1983),
Lancet (1983) and Clinical & Experimental Dermatology
(1984).
Since then, the
syndrome has come to be recognised as an important medical
condition – both common and potentially treatable –
a cause of migraine, miscarriage, stroke, heart attack –
and a wide variety of other features.
Frustrated by the
seemingly slow recognition of the syndrome, some years ago,
we formed our charity – Hughes Syndrome Foundation –
in order to try to increase awareness – both amongst
patients and doctors.
This year, 2009,
our charity was joined by two outstanding “new brooms”.
Lynne Kirwin and Linda Fischer. More of Linda below. Lynne,
a patient of mine with a lifetime background in the media,
has already had a huge impact on our efforts to “spread
the word”. One of her many suggestions has been to start
a monthly “blog” on our website, updating those
who are interested in all that is going on in research, in
treatment and in news in general.
I never considered
myself a “blogger”, but to update everyone on
what’s going on around the world with Hughes Syndrome
– yes, I’m happy to give it a try”.
House of
Commons
I mentioned Linda
Fischer. An American lady now living in London, and a patient
of mine, she has brought with her a long experience of patient-based
awareness campaigns in the USA, as well as a wonderful combination
of energy and focus. She has had an immediate impact on our
charity. She was the catalyst who encouraged me to publish
my patient book “Hughes Syndrome : 50 Clinical Cases”.
She also thought that public knowledge of the syndrome was
still poor (rather as with lupus thirty years ago) and immediately
set about doing something to change things.
It so happens that
the Government is currently running a campaign to educate
the public about stroke. Very important – yet we now
know that Hughes Syndrome underlies up to 20% of stokes in
the under 45’s! No mention of that in Government papers.
What better that a book launch in the House of Commons?
Think big! So, together with Lynne Kirwin and Baroness Estelle
Morris, and aided and abetted from the Hughes Syndrome Foundation
by Kate Fitzpatrick and Sandy Hampson, the evening of 5th
February was chosen for a small reception. Estelle Morris
was wonderful as the hostess – actively taking part
in all the planning as well as contributing a wealth of ideas.
And on the night,
friends, helpers, MP’s and members of the press heard
more about the syndrome and the research work going on in
its causes and treatment.
The two speeches
by Estelle Morris and Linda Fischer were among the best I
have ever heard. I think we all came away optimistic that,
at last, the awareness campaign was really about to take off.
January
2009
I never thought
I’d become a blogger! Family and friends cannot believe
it. Yet it was family and friends who piled on the pressure
for me to write a monthly ‘blog’ (more a diary
perhaps) to supplement the Hughes Syndrome Foundation website.
In the 26 years
since we described the antiphospholipid syndrome, recognition
of its importance in medicine, surgery and obstetrics has
gathered pace. Slowly at first, but more rapidly now, with
journal publications, national and international conferences
(the next world conference on Hughes Syndrome will be in Texas
from 13-16 April 2010).
The clinical features
of the syndrome: thrombosis, migraine, miscarriage, stroke,
low platelets, memory loss and kidney and liver thrombosis,
described in our 1983 papers have expanded to include movement
disorders, balance problems, atypical MS, angina, infertility,
visual symptoms and bone fractures (to name but a few).
Clearly the effects
of ‘sticky blood’ can be felt in any organ of
the body, and Hughes Syndrome features in the clinics of heart
specialists, ear nose and throat specialists, orthopaedists,
psychiatrists and, of course, general practitioners.
Especially general
practitioners. A simple rule of thumb of 1 in 5 highlights
the frequency of Hughes Syndrome in some common disorders
( ‘1 in 5‘ quoted here comes from published work).
Hughes Syndrome
is implicated in 1 in 5 cases of:
Deep vein thrombosis
Recurrent miscarriage
Young strokes (under 45)
Young heart attacks (under 45)
Systemic lupus
Clearly in light
of our knowledge, there is a strong argument for antiphospholipid
(aPL) blood testing in any of the above conditions, as well
as in severe migraine and a number of other conditions.
Frustratingly,
testing in these situations is not routinely carried out.
The Hughes Syndrome Foundation has made it its prime objective
to improve awareness of the condition. I am sure it will succeed.
For me, the state
of public knowledge about Hughes Syndrome resembles that of
lupus forty years ago when I first set up my lupus clinic.
And how that has changed, with lupus seemingly cropping up
almost weekly in the TV series ‘House’.
My plan, in writing
this monthly blog, is to begin with an update on new research,
meetings etc, and to follow this with a ‘patient of
the month’ – a case report based on a true medical
history, each case report hopefully teaching us a lesson,
following the formula started in my book ‘Hughes Syndrome:
50 clinical cases” (Springer).
I hope the blog
becomes a useful medical diary. Please don’t let it
ever become boring!
Graham Hughes
The London Lupus Centre
London Bridge Hospital
www.thelondonlupuscentre.com
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