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Make your experience count!

Each of you has different experiences of having Hughes Syndrome from chasing a diagnosis to following treatment. Sharing these experiences can be helpful in many ways – for research and information, for support and sometimes just to vent. So now we want to help you share in a new way … blog about them.

You don’t need to have done this before, you just need to write about things others affected by, or interested in, Hughes Syndrome can relate to and understand.

Maybe you’re suffering personally, or supporting someone else who is; maybe you work in the field and want more ways to learn about the disease or help with it. Whatever the reason, your experience counts and you can share it through a blog.

The Hughes Syndrome Foundation free online resource managed by HealthUnlocked includes other things apart from blogs like reviewing the service you’ve had at a hospital or voting on a hot topic. However you participate, it’ll be your content that will make the site a success.

Remember, even if you don’t become a blogger, you can comment on other people’s posts once the site is launched. Don’t hold back – wouldn’t you like your words to make a difference? Please join the Hughes Syndrome Foundation's HealthUnlocked forum.

Professor Hughes' blog ...

May 2011

April 2011

March 2011

February 2011

January 2011

December 2010

December 2011

This is my last blog for some months.

Our young charity is growing fast.

Thanks to the efforts of Lynne Kirwin and Kate Hindle, and their dedicated helpers, we are beginning to see a mushrooming of interest in the syndrome, and some tangible results. For example, the survey carried out by Mary McDonald and Professor Peter Donnan on the awareness of Hughes syndrome, provided the basis for a paper (Antiphospholipid antibody testing – slow progress?) which is to be published shortly in a major medical journal: the International Journal of Clinical Practice.

We recently welcomed Estelle Morris, Baroness of Yardley, to Chair of our trustee meetings. Estelle, a prominent member of the House of Lords, former MP and member of the cabinet has already proved a great friend to our charity and a loyal supporter of our work.

Talking of supporters, this month was the tenth anniversary of the death of Louise Gergel whose parents are John and Linda Wolffe. Over the past ten years, John and Linda, along with their friends and family, have raised enough money to fund the salary of an APS research fellow – a truly superlative effort – and a wonderful homage to their lost daughter.

This year saw the publication of three new books (rather like London buses). Two were produced by Dr Shirish Sangle and myself and published by Springer – Hughes syndrome and Lupus, both in the Springer series of books for students. The third, published earlier, Tales of the Flying Doctor (and the story behind Hughes syndrome) was published by Hayward Medical Communications and gives, I hope, a humorous account of life as, first, a medical student, and second, of a fledgling doctor.

December is not a month to travel – tube strikes, packed airports. Luckily for me, therefore, there was only one overseas talk. A Saturday morning meeting on advances in medicine - in Brussels. A meeting organised by Professor Fred Houssiau – now a leading Belgian expert in lupus and other topics (including Hughes syndrome).

And the joy! The Eurostar – boarding and train in London (St Pancras) and arriving a mere two hours later in Brussels! The only way to travel!

This is the 36th monthly blog. Three years. I felt that it was time to pull back a little. I plan to continue the blog, but on a quarterly basis. I hope that this series of 36 ‘cases of the month’ has proved helpful. I am touched by the feedback you have offered. Many thanks.

Case of the Month

‘Taking the history’ from a patient is the first and most important part of a medical consultation. Sometimes the enormity of the process is overwhelming.

Mrs S.U. arrived for her appointment without a GP’s referral letter or any other documents – there had been some confusion. The 51 year old was, however, calm and unflustered. Bit by bit the history unfolded …

Doctor: “Did you have any childhood illnesses?”

Mrs S.U: “Not until the age of 14 when I had a fit in the middle of York market”.

Doctor: “Was any firm diagnosis made?”

Mrs S.U: “I was seen by a specialist and had tests. At first, there was no clear diagnosis. But the I had two further seizures, and for a year or two, I was put on epilepsy tablets”.

Doctor: “Any headaches or other symptoms?”

Mrs S.U: “I started to get frequent headaches, as well as funny pins and needles in my arms and legs. The doctors suspected multiple sclerosis. However, things didn’t progress, and in my twenties I was well apart from occasional migraine”.

Doctor: “Did you have any pregnancies?”

Mrs S.U: “My first pregnancy ended at eight months, when the baby died. The doctors couldn’t find a cause. The little boy seemed normal. Then I had two successful pregnancies and I have two healthy grown up daughters. My fourth pregnancy miscarried at four months. My husband and I decided then that ‘enough was enough’”.

Doctor: “In your thirties?”

Mrs S.U: “I was reasonably well, working full time in an office. I suppose it was about the age of forty, ten years ago, when new things happened. I started to suffer quite severe tummy pains – oddly enough, about an hour or so after a meal”.

Doctor: “Was any cause found?”

Mrs S.U: “No. I had scans and an endoscopy. Nothing. I tried Gaviscon and Zantac, and even tried a gluten-free diet but nothing really helped – apart from taking more frequent meals.

Doctor: “Any other symptoms?”

Mrs S.U: “Well, over the past two to three years, I have had a number of attacks of giddiness – first I was told it was Menieres disease, but I think they are not so certain now. Then, for the past few years, I have had a mixture of fatigue and aches and pains. The headaches have been bad”.

Doctor: “Any memory problems?”

Mrs S.U: “Oh yes! I used to have a wonderful memory but recently, it seems to have deserted me. I even forgot to collect the GP’s letter I had promised to bring to this appointment. I am a little concerned because I have had two episodes of numbness down one side of my body. It was then that my doctors started aspirin”.

Doctor: “Although, I don’t have a GP’s letter, clearly the diagnosis of Hughes syndrome was suspected?”

Mrs S.U: “The story is interesting: something of a ‘Eureka moment’ in fact. One evening, my husband came running upstairs – “I’ve got it”. And he had! He had been scouring the internet and had come across the Hughes Syndrome Foundation’s website (www.hughes-syndrome.org)”.

All the features added up. Made sense. And to their credit, Mrs S.U’s hospital doctor and GP followed up on the suggestion that Hughes syndrome was at least a part of the complex puzzle. They re-investigated her and found positive antiphospholipid antibody (aPL) tests. She was also found to have dry eyes (possible Sjogren’s) and a slight heart murmur – thought not to be serious. Her doctors started her on aspirin and Plaquenil.

What is this patient teaching us?

Firstly, of the many alternative diagnoses this patient received – migraine, epilepsy, multiple sclerosis, fibromyalgia, celiac, Sjogrens etc, some were helpful, some not.

Secondly, Hughes syndrome is complex. Like other autoimmune conditions such as lupus, it can present in a wide variety of guises.

Mrs S.U.’s early features included fits and migraine. A study carried out by Cimaz et al in Milan suggests that up to one in five cases of idiopathic (where no obvious cause is found) epilepsy were found to be aPL positive.

The tragic pregnancy history is also telling. The loss of a baby at eight months may have a number of causes – but high on the list is the potentially preventable condition, Hughes syndrome.

Later features include abdominal pain – possibly ‘abdominal angina’ – pain after a big meal because the blood supply needed for digestion is impaired. Add to that Sjogren’s (dry eyes, and aches and pains), heart murmurs, balance problems and memory loss – no wonder Mrs S.U.’s husband rushed up the stairs!

Mrs S.U. may well require more substantive anti-clotting treatment, such as warfarin. She is one of Britain’s heroes. I think she will do well.

November 2011

The second warmest November on record! Another record! (at least here in the south). This time last year we were under a (record?) heavy snow fall.

November brings the annual American College of Rheumatology (ACR) meeting. Far and away the best international meeting in our field, especially for those working in lupus. I have not been for three years, but this year was invited to run two consecutive ‘meet the professor’ breakfast sessions. These sessions are limited to thirty or so pre-booked attendees, and cover dozens of topics. I’m pleased to say that the ‘antiphospholipid’ session was fully booked. It was also very encouraging to see that the first nineteen papers in this massive meeting were all on our syndrome. Interest is spreading!

The other November meeting was in York, arranged by a group called the Primary Care Rheumatology Society. This is a group of GPs who have a special interest in rheumatology. I gave a Friday lecture on ‘the big three’ (lupus, Sjogren’s syndrome and Hughes syndrome) adding, I hope, to the spread of awareness of these conditions. For me it was a thoroughly enjoyable day (I had never previously visited this beautiful city).

Case of the Month

Mrs GJ, aged 41, had been referred by a physician colleague as a possible case of Hughes syndrome. She had had one suspected (but not proved) leg clot (DVT) in the past, and had a long history of headaches, balance problems and ‘pins and needles’.

Her sister had suggested that she be tested for Hughes syndrome, and the tests did, in fact, turn up a positive anticardiolipin result (aCL). All other tests were essentially negative, and an ‘unproven’ diagnosis resulted. She was started on low dose aspirin. Some nine months later (despite some improvement in the headaches) she developed a more definite DVT and was started on warfarin.

She was investigated for a range of clotting disorders and, once again, the only positive test was a medium-to-strong positive anticardiolipin (aCL) result.

Her family history (once again) was interesting. She had two sisters with multiple sclerosis (MS), another with migraine, and a fourth sister with Hughes syndrome.

What is this patient teaching us?

Once again, the family history can be important in diagnosis. As well as a sister with Hughes syndrome and another with migraine, she had two other sisters with MS. For me, the link (or relationship) between Hughes syndrome and MS is tantalising. Some years ago, we ran a questionnaire in our clinic at St Thomas’ Hospital. We asked the question ‘did your doctor at any time consider your diagnosis to be MS?’ The result was striking - over 30% of patients with positive antiphospholipid tests replied ‘yes’ – compared with 8% of the remainder of (mainly lupus) patients.

I believe that there are three possible reasons for the observation:

1. That the two conditions, with balance and visual disturbances, sensation loss and other ‘neurological’ features can be hard to distinguish (my own preferred explanation).

2. That MS – also considered an autoimmune disease – is one of the spectrum of diseases (such as low thyroid) seen in ‘autoimmune families’.

3. That MS, like, for example, arthritis, is made up of a number of causes, each targeting the nervous system.

Given the importance of MS, to me it is very surprising that still, thirty years after our description of the antiphospholipid syndrome, there are few good studies of this conundrum.

October 2011

A lovely autumn – still dry in the South East.

It’s hard to believe that the London Lupus Centre has been going for five years! We estimate that we have now seen lupus and Hughes syndrome patients from 72 countries! Working here at London Bridge Hospital is a treat – overlooking the pool of London, between London Bridge and Tower Bridge, the area around the hospital, with the new ‘Shard’ skyscraper, Southwark cathedral, Borough market, and London Bridge station, has a real ‘buzz’ about it. Of course, we also have the London Dungeon and the ‘London Experience’ nearby, sometimes with ghosts, skeletons and ‘dead bodies’ out on the pavements – not a particularly good advert for our hospital!

Our annual ‘Ten Topics in Rheumatology’ is spreading worldwide, with ‘Ten Topics’ meetings now held in Barcelona, Nice, Rome and the Far East (Manilla last year, Hong Kong this year). This month ‘Ten Topics’ were held in Beirut (with Chris Edwards from Southampton and our unit lecturing, and Argentina (with Laura Bertolaccini and Maria Cuadrado taking part); these two meetings had 200 and 800 attendees respectively. I like to think that the Ten Topics meetings have contributed to teaching about lupus and about Hughes syndrome.

Case of the Month

Mrs K U, aged 41, gave a three year history of ‘chronic fatigue syndrome’ as well as aches and pains, and a tendency to ‘irritable bowel’. An initial diagnosis of ‘fibromyalgia’ (fatigues and aches and pains) was made.

A year later, in 2009, she developed slight shortness of breath, dry mouth, and frequent headaches. The headache became more severe, and frequently migrainous, so much so that on one occasion she was admitted to hospital in ‘status migrainosus’. A brain MRI was normal as was a chest x-ray. Subsequent investigations showed a positive ANA (anti-nuclear antibody) and a positive anticardiolipin test (strongly positive).

Clinical examination did not reveal any cause for the shortness of breath, but she did have two important critical signs. Firstly, she had a bone-dry Schirmers test (a simple test in which a strip of standardised blotting paper is hooked over the lower eyelid). The blotter is usually soaked in seconds. In Sjogrens syndrome (see below) it can remain dry for the full five minutes of the test.

Secondly, she had prominent livedo reticularis (blotchy ‘corned beef’ skin) on the forearms and thighs.

She was started on Plaquenil with (after a month or so) improvement in her aches, pains and fatigue.

The headaches remained. Aspirin failed to help. She suffered a mini stroke despite being on aspirin. A three week trial of heparin helped to improve the headaches.

She was ultimately started, in 2010, on warfarin, keeping the INR high at 3.5-4.

Six months later, she was a ‘changed person’. Not only had the headaches gone but, interestingly, the blotchy livedo skin had improved. As an added bonus, both the shortness of breath and the ‘irritable bowel’ had improved with the starting of warfarin anticoagulation.

What is this patient teaching us?

The story of this patient is a recurring theme: the association of Hughes syndrome (migraine, stroke and fatigue) with Sjogrens syndrome (dry eyes and mouth, aches and pains, positive ANA).

The improvement of patients with this clinical combination after starting Plaquenil and anticoagulation is often striking. The disappearance of the livedo is something we often see following successful warfarin anticoagulation.

In this patient, the shortness of breath improved (it is conceivable that this patient was suffering from mini lung clots). More surprisingly, the ‘irritable bowel’ symptoms immediately improved. A coincidence? I have certainly seen irritable bowel symptoms in a small number of our Hughes syndrome patients improve with anticoagulation. One possible explanation is that ‘bowel ischaemia’ (a sludgy blood supply to the bowel) might be contributing.

Finally, any clues to the cause(s) of Hughes syndrome? Yes. Two clues – ‘genetic’ and ‘enviromental’. Mrs K U had a strong family history of autoimmune disease (thyroid and rheumatoid in her family).

Secondly, her history possibly went back over twenty years. At the age of 21, she went down with severe glandular fever. She was laid up for over a month. She did not completely recover, fatigue, aches and pains and intermittent headaches, dating precisely from the glandular fever, continued for several years, before easing up, only to return in her late 30s.

Although final proof of a link between some cases of glandular fever (E-B virus) and autoimmune disease such as Sjogrens and Hughes syndrome remains elusive, the clinical suspicion is strong.

September 2011

Another record! – the first of October earlier this week was the hottest October day on record (as always, the record was recorded in Gravesend, Kent). “Hotter than the Sahara”.

This month was an important one for our charity. Estelle Morris (the Right Honourable Baroness of Yardley) has agreed to become the Chair of our charity. Estelle, a member of the House of Lords and MP for Birmingham Yardley, was the minister of education in the previous government.

She has become a friend and loyal supporter of our Louise Coote Lupus Unit at St Thomas’ Hospital and patron of the Hughes Syndrome Foundation for several years, and we are all absolutely delighted that she has agreed to become Chair.

Two lectures in September: one in Hong Kong and one in London. The Hong Kong meeting was high quality, organised by an old friend Chak Lau and with a keen audience – very knowledgeable about Hughes Syndrome. For me it was something of a whirlwind – out Thursday night-Friday, lecture Saturday, home Sunday. My theory is that if you come straight home, the body doesn’t have time to think about jet-lag (almost certainly wrong).

The second talk, here at the King’s Fund in London, was at the Anticoagulation Education Day organised by Anticoagulation Europe – many thanks to Michael and Eve Knight for their tremendous hard work. The audience consisted mainly of nurses and clinicians working in anticoagulation clinics.

Hughes Syndrome patients often require a high INR – especially those with headache or balance problems. In the past, this has often led to difficulties in the anticoagulation clinic, where lower INRs – for example 2-2.5 are the norm. This year at the Anticoagulation Education Day, there was a far wider acceptance of the need for better control in Hughes Syndrome patients, but also of the value of self-testing INR kits and their use in parallel with the anticoagulation clinic’s control.

Case of the Month

This patient, a 41 year old Guyanese lady, came up to me after the London meeting. She had had a long history of lupus, treated variously with Plaquenil and steroids over the years, and without severe kidney damage. Two years previously, she developed increasingly severe headaches, marked fatigue and widespread aches and pains. She then developed a DVT in the leg and was started on warfarin.

Before the warfarin treatment, her pains had never really totally left her. Since the start of warfarin therapy, almost all her symptoms have abated.

What is this patient teaching us?

Yes, she was (belatedly) found to have antiphospholipid antibodies (aPL). And her history suggests that in those 1 in 5 lupus patients who are aPL positive, a significant constellation of clinical features may be more down to circulation problems (‘sticky blood’) than to the inflammation of lupus. An important lesson.

As a simple rule of thumb, remember 1 in 5. All the published experience keeps coming up with a roughly 1 in 5 percentage in Hughes Syndrome.

‘One in Five’

1 in 5 lupus patients are aPL positive
1 in 5 strokes (under 45) are linked to aPL
1 in 5 recurrent miscarriage cases are aPL positive
1 in 5 cases of DVT are aPL positive

A 1 in 5 figure for aPL positivity has been reported in idiopathic teenage epilepsy: in future there may be more – memory problems, low platelets – and so on.

The medical, financial and sociological implications are huge.

August 2011

Last day of August. Grey and cold. “The coldest summer for eighteen years” – how we British love our records!

Earlier this month, I gave two lectures in Colombia, South America – two days in transit, two days in Colombia. What a wonderful reception – several hundred young doctors, keen and hungry for information. One told me that they have an ‘epidemic’ both of lupus and Hughes Syndrome – now two of the most commonest illnesses they face.

It was especially good to meet with two friends – Herman Gonzalez who had been a visiting fellow in the Louise Coote Lupus Unit at St Thomas’ 25 years previously, and Antonio Inglesias, Professor of Rheumatology in Colombia who has produced a massive two-volume history of lupus – a masterpiece.

The closing dinner on the evening of my lecture was also memorable. A major football match was being played that evening between Colombia and Mexico. A giant TV screen was erected, and we were all given yellow shirts and caps (Colombia). Colombia lost, but still great fun.

August also brought a new role. I was invited to become a patron of Britain’s national arthritis charity, Arthritis Research UK. I met their team, led by their new chief executive Liam O’Toole and also their director of philanthropy, Jacqui Manning. A real sense of optimism and purpose. I have no doubt that the charity will thrive, and break out of its old ‘clubby’ reputation. I will certainly do my best to help.

Finally, Kate Hindle gets married this Friday. All of us here wish her every success and happiness.

Case of the Month

Mrs AL, a 50 year old lady from Plymouth, was referred to the London Lupus Centre for a second opinion. Her history was complex. For some years she has suffered circulation problems, with two DVTs, one documented pulmonary emobolus, migraine, angina, transient ischaemic attacks (TIAs) and finally a slight stroke. She had also, in her twenties, suffered three miscarriages.

Also, for a number of years, she had suffered from widespread muscle and joint pains and aches. One physician had diagnosed fibromyalgia, which seemed to fit the pattern of her symptoms.

Her family history (important) was interesting. Her father had suffered autoimmune haemolyptic anemia, migraine and an early stroke. Her daughter had had five miscarriages but not been tested for antiphospholipid antibodies (aPL).

On examination, apart from evidence of slight residual weakness from the stroke, there were no abnormal findings in Mrs AL – with one notable exception. Testing her eyes for dryness (the so-called Schirmer tear test) showed a complete lack of tears – a finding suggesting Sjogren’s Syndrome.

What is this patient teaching us?

Clinically, a diagnosis of Hughes Syndrome is fairly clear – a diagnosis confirmed by the finding of strongly positive tests for aPL. She has been started on warfarin.

The history of ‘fibromyalgia’ is interesting. Although it is a common diagnosis, it can be misleading. For example, many of my lupus and Sjogren’s patients have initially been diagnosed with this label. In Mrs AL’s case, the diagnosis is almost certainly Sjogren’s Syndrome (dry eyes, dry mouth and aches and pains) – a syndrome which often goes hand in hand with ‘sticky blood’.

Normally in these blogs, there is a conclusion to the story. Not yet with Mrs AL. She has been started on Plaquenil for the Sjogren’s aches and pains and warfarin for the Hughes Syndrome. I promise to give an update in a few months.

July 2011

The first of July saw the final day of our annual ‘Ten Topics’ meeting – the 25th (and in my view, the very best) Ten Topics ever. Our speakers in the ‘masterclass’ series included Professors Cathy Nelson-Piercy and Lucilla Poston (pregnancy in lupus and Hughes Syndrome), Professor Fred Houssiau from Brussels (treatment of kidney disease) and Professor Yehuda Shoenfeld (Israel) who gave an overview of causes of disease entitled “The Mosaic of Autoimmunity”.

Dr Khamashta presented interesting data on our patients with clinical Hughes Syndrome in whom standard antiphospholipid tests are negative. During his three month sabbatical in America, he studied serum samples from a group of ‘sero-negative’ APS patients, using a batch of newer, sensitive tests. Guess what? Many showed positive tests in these refined analyses although such sophisticated testing is not yet available routinely, it does reinforce the feeling that our current tests still leave something to be desired.

While on the subject of newer tests, an interesting collaborative study from Hungary, Israel and Norway was published in the journal LUPUS. In it they found that antibodies against oxidised LDL (low density lipoproteins) were associated with the tendency to acute coronary disease. The relevance of this finding is that some patients with lupus and some with Hughes Syndrome develop angina. Oxidised LDL has long been implicated in causing atheroma and altering their structure by antibodies is a potentially important step in the process. I’m sure this family of antibodies will one day be incorporated in standard cardiology/health screening.

Thank you to the Wolffe family who are doing so much to support our fundraising efforts. On Thursday 21st July, they held a fundraising event at 11 Downing Street, residence of the Chancellor George Osborne. The event was organised by Anna Petrook, Louise’s sister, who works in the office at number 11. It was a splendid do, including speeches by Anna and by George Osborne – very generous considering that the chancellor was in the thick of the European financial meltdown!

Thank you also to those of you who have written such supporting letters regarding the break up of the Louise Coote Lupus Unit at St Thomas’. Although I am long retired from St Thomas’, the whole affair saddens me a lot. In the year when six European centres are setting up lupus clinics based on the St Thomas’ model, it is particularly poignant.

Case of the Month

Mrs P J, aged 37, had a past history of severe migraines and three miscarriages. Her mother had suffered from migraine and stroke (and had also had a full term pregnancy loss).

An interesting feature of her history was that following aeroplane flights, she invariably suffered migraine attacks, sometimes lasting for days.

Finally, after suffering two TIAs (transient ischemic attacks), she was started on warfarin.

She is now very well. No headaches. ‘Fit as a fiddle’. She monitors her own INR in collaboration with her local clinic.

What is this patient teaching us?

I suppose this patient’s history rings many bells – certainly it is a story I hear every day in my clinic at London Bridge Hospital.

Three messages: firstly, always get a detailed family history. Secondly, warfarin, despite its ‘bad press’ is a useful drug – and in many Hughes Syndrome patients, life changing.

The third message is a particular interest of mine – the history of altitude problems in some of our patients – something on which I am going to arrange a survey in our Hughes Syndrome Foundation members.

June 2011

A very late blog. I had privately planned to stop this month, but Kate flattered me by asking me to continue. So …

One of the main reasons for the delay is that there are major changes going on in the Louise Coote Lupus Unit at St Thomas’. It seems that those in power have decided to re-link the unit with rheumatology.

Although most of my colleagues there have, so far, received little or no information, things are already changing. The Louise Coote Lupus Unit will hold rheumatology clinics, and our lupus and Hughes Syndrome patients may be shunted to general rheumatology clinic in Guy’s Hospital, or to haematology on the fourth floor at St Thomas’. Some of this has already happened. This week the charity offices of the Hughes Syndrome Foundation and the St Thomas Lupus Trust moved to an empty ward in Guy’s Hospital – Kate and Angie have kept their old phone numbers but have little else at present.

Although I am long retired from St Thomas’, it saddens me to see the world famous unit being divided up – especially at a time when six major clinics across Europe are setting up units based on our model – a unit bringing together specialists and staff expertise in dealing with these complex disorders. And patients not having to travel from pillar to post …

Two interesting meetings this month. The first was our annual Ten Topics meeting at St Thomas’ Hospital. A very special meeting – the 25th anniversary. As always, the two day meeting (held this year on 30th June and 1st July) was fully booked, with doctors registering from all over Britain and the continent, and attendees from as far afield as Lebanon, Israel, South Africa and one brave doctor making it from Libya.

This meeting covers all the major advances in rheumatology, with especial emphasis on lupus and Hughes Syndrome. The 25th meeting, including a number of speakers making ‘comebacks’ from previous meetings was, in my view, the best ever.

The second meeting was rather different – a guest lecture in China (Changsha) – a whirlwind visit – travel out on Thursday/Friday, lecture on Saturday, home Sunday! My naïve theory is that you don’t get jet lag if you make the visit short!

The meeting was great, with over 1000 attendees – very keen interest in Hughes Syndrome. As with lupus, there appear to be very large numbers of people in China already diagnosed with Hughes Syndrome. And as with other aspects of medicine, there is a dramatic increase in the research effort into these two diseases, as evidenced by the exponential growth of papers submitted to the international journal LUPUS.

Case of the Month

A 30 year old man was referred by an Ear/Nose/Throat (ENT) colleague with a history of acute hearing loss in one ear. Interestingly, blood tests had turned up two positive tests for anticardiolipin antibodies (aCL). Could there be a connection?

The man’s previous health had been good, with nothing to suggest thrombosis or underlying disease. The family history threw up no clues. He had, however, suffered from severe migraine in his late teens and early twenties – often as frequently as one every third or fourth day.

Our own investigations proved intriguing. He had negative aCL and lupus anticoagulant (LA) tests on this occasion, but had a strongly positive anti-beta2-glycoprotein1 test.

We have started low dose aspirin, but may have to change to clopidogrel (Plavix) if there is any negative further effect on his hearing.

What is this patient teaching us?

ENT problems, especially balance problems, are becoming well recognised in Hughes Syndrome. Whether this patient’s hearing loss is a direct result of ‘sticky blood’ is of course uncertain, though his past history of severe migraine does suggest a clinical link with antiphospholipid antibodies (aPL).

For me, there is another lesson. Our testing for aPL is still imperfect – there are laboratory differences, and there are an increasing number of patients seen who have all the hallmarks of Hughes Syndrome, but with negative tests.

The development of newer tests is proceeding apace. One test now increasingly added to the two routine tests (aCL and LA) is the prosaically named anti-beta2-glycoprotein1 antibody test – usually shortened to ‘Beta 2’. While our experience so far has not turned up many ‘aPL-negative’ patients where the Beta 2 is the only positive clue, it certainly opens ones eyes. Watch this space.

May 2011

What a month!

Here in Kent, it has been wall to wall sunshine. Rain on one single day in our garden (last Thursday) – garden parched, but Provence-style blue skies and wonderful gardens for the whole month. We, the British, have a nerd-like fixation on weather ‘records’ – ‘the wettest since last week’ etc. But this morning’s paper proclaimed this spring (in the south East corner at least) “the driest since records began in Oliver Cromwell’s time”.

Two meetings this month – the annual ‘EULAR’ meeting (European Rheumatology), held this year in London. A meeting of over 14,000! I dipped in for a day – a well organised meeting covering all aspects of rheumatology (including a session on antiphospholipid syndrome). The other meeting was the annual patients’ forum on Hughes Syndrome at St Thomas’. This is, both for the patients attending, as well as for me, a marvellous afternoon meeting, where the ‘question and answer’ sessions pulsate. So much is exchanged. So much is learned. The session on self-testing INR (warfarin control) was especially noteworthy – with patients (and doctors) dragging the subject into the 21st century. If diabetics can be trusted with self-monitoring, why not warfarin/INR patients?

The month of May ended with an evening reception for lupus research workers at the residence of the American ambassador, Louis Susman, at Winfield House in Regent’s Park. The driving force for this link with lupus (and Hughes syndrome) is Majorie Susman, who, before her posting to London, was an active and effective lobbyist for lupus in the USA. A fantastic ally in our efforts to spread awareness of lupus and its related diseases.

Case of the Month

Mrs P.Y., a 37 year old housewife, developed severe headaches, back pain and, ultimately, paralysis of the lower limbs. MRI tests showed lesions in the brain and spinal cord, and a possible diagnosis of multiple sclerosis (MS) was made. Investigations, however, showed very high levels of anticardiolipin antibodies (aCL).

Her past history was interesting, and possibly relevant. Fifteen years before she had had silicone breast implants. At first, these had been trouble-free, but after a few years began leaking and became lumpy and painful. It was about this time that she began to complain of new symptoms – headache, fatigue, aches and pains, and ultimately, partial lower limb paralysis.

The local medical team investigated. As well as very high titres of aCL, biopsy of an enlarged armpit lymph node revealed silicone-altered particles. The ruptured silicone breast implants were removed and non-silicone replacements substituted.

What is this patient teaching us?

Possibly too early to say. But the breast surgeon involved in the case felt that he had seen a number of ‘neurological’ symptoms in patients with ruptured silicone breast implants.

Could there be a connection? There has been a long recognised link between silicone implants and medical problems. Silicone is known to be an ‘adjuvant’ – a ‘kicker-upper’ of the immune system, and prominent amongst the wide effects reported following silicone implant problems have been autoimmune features such as Sjogrens syndrome (lupus-like), anti-nuclear antibodies, and, yes, anticardiolipin antibodies.

April 2011

After the long, cold, windy, wet winter, a dramatic change - dry and hot! Easter was the hottest on record and the country basked in the sun over the long weekend - and on until the royal wedding.

Every two years or so, a European lupus meeting is held, rotating from city to city. This year was Porto's turn, a pretty northern Portuguese city famous, of course, for its port.

This year's congress was organised by three very good 'lupus' friends. Carlos Vasconcelos of Porto, Ricard Cervera (Barcelona) and Munther Khamashta (St Thomas' Hospital).

Although the conference focuses on lupus, I'm pleased to say that there is an increasing recognition of Hughes Syndrome and the importance of antiphospholipid antibodies. Although the two conditions are different, up to 20% of lupus patients carrying antiphospholipid antibodies are subject to the same clotting and miscarriage complications as those with Hughes Syndrome.

The opening ceremony was, for me, memorable for two reasons. Firstly, I was presented with a special lifetime award for my work in lupus and antiphospholipid syndrome.

This was the first time such an honour had been given at this international meeting. The programme headed the event as 'homage to a simple physician'. I'm not sure about the 'simple' bit, but it was a huge honour for me (and, I hope, for British medicine).

The second highlight of the evening was the singing of traditional Fado - two instrumentalists, a girl with a beautiful and dramatic voice intoning the emotive, melancholic - almost Arabic - music. Unforgettable.

Case of the Month

A 43 year old lady from Selby Oak, near Birmingham, was referred by her GP for a second opinion. Her present complaints were of severe headaches, balance problems and memory loss. She had been diagnosed as having Hughes Syndrome and was on 'baby' aspirin.

Her history was remarkable.

At the age of fifteen she developed seizures and was diagnosed as having epilepsy. At eighteen, balance problems started, together with some neurological symptoms. She was labelled as 'multiple-sclerosis' and treated for a period with some of the newer drugs being tried in MS. At the age of twenty, she experienced menstrual irregularities and was started on the oral contraceptive pill - with severe consequences: the headaches to which she was prone became severe and migrainous. Within two weeks she developed a leg vein thrombosis and pulmonary embolism. She received warfarin for eight months and was then changed back to aspirin.

Over the past three years, she had felt that the headaches were worsening, as was her memory. Investigations included a brain MRI which showed no abnormalities.

However, three months previously she suffered a TIA (transient ischemic attack), and four weeks before her London Lupus Centre appointment, a more prolonged stroke, from which she was slowly recovering.

She was known to have positive anticardiolipin (aCL) tests - in the low to moderate range, and had also been found to have borderline low platelet counts.

As she was leaving the room, I asked about pregnancies. Thirteen miscarriages. No children �

What is this patient teaching us?

The history of this uncomplaining lady came out like hammer blows. Hughes Syndrome with migraine, 'multiple sclerosis', DVT, pulmonary embolism, positive aPL, low platelets and memory loss. And now one, maybe two, strokes! And treatable! With warfarin - probably to an INR level in the high 3 range - she will be so much better. And hopefully, free from further strokes.

I suppose the lesson from this gentle, long-suffering lady is of the complexity of the syndrome, and the epic 'journey' some patients face before being correctly diagnosed and treated.

For my part, I felt humbled that in the unfolding of her complex history, I almost forgot to ask about her pregnancy history �

Thirteen miscarriages!

March 2011

The week after my visit to Japan, the earthquake and tsunami struck. To think that five days earlier, my plane from Sapporo down to Tokyo passed over the area devastated by the disasters. Our team in the London Lupus Centre emailed our wishes and hopes to colleagues in Sapporo – Dr Koike, an old friend and eminent lupus doctor. Two of his research fellows – Dr Astsumi and Dr Olga Amengual (from Spain) met while on sabbatical in our unit in London, married and now live happily in Japan. The calm dignity and orderliness of the Japanese during this devastation is an example to us all.

In terms of ‘news’, March has been quite quiet, with daily clinics and no major medical events. Next month, April, promises a lot. The European conference on lupus (with a significant input on Hughes Syndrome) is being held in Porto, while in London, preparations are in place for the annual EULAR rheumatology meeting – some 14,000 attendees! The good news is that our syndrome is being represented, thanks to the efforts of Kristina Bailey and the American APS Association who managed the impossible in obtaining an exhibition stand for FREE! Kate and her colleagues will be there.

Also in April is the launch of my own book (apologies for the plug), called ‘Tales of a flying doctor and the story behind Hughes syndrome’* – an autobiography of our work leading up to the discovery of the antiphospholipid syndrome. Not Jeffrey Archer, I’m afraid, but I hope it’s an enjoyable read!

Case of the Month

A 41 year old man complained of pins and needles, weakness in the legs, difficulty in walking and, occasionally, difficulty in passing urine. He was investigated by a specialist. An MRI showed a lesion in the spinal cord, and a diagnosis of multiple sclerosis (MS) was made.

The patient was not totally convinced. He had had other symptoms which didn’t quite fit – severe migraines, cold hands and feet, and occasional episodes of arthritis.

He was seen by a second consultant, a neurologist, who agreed that, at best, this was atypical MS. A further blood test revealed high levels of antiphospholipid antibodies (aPL) – very high, at over 200 units.

He was referred to the London Lupus Centre where a probable diagnosis of APS was made.

He started a course of warfarin. Dramatic initial improvement, but after six months, the symptoms worsened again. MS after all? His INR record, however, gave a clue. Readings regularly in the 2-2.5 range.

Too low a dose: rather like treating diabetes with too low a dose of insulin. For the past four years he has remained symptom-free, keeping his own INR sticking at 3.4-4.

What is this patient teaching us?

I make no apologies for coming back to the story of Hughes Syndrome and MS.

For three reasons…

Firstly, a number of the features of Hughes Syndrome can mimic MS – the sensory loss, the balance problems, the spinal cord lesions. Secondly, it does often seem that these patients with prominent neurological features of Hughes Syndrome may need a higher INR.

Thirdly, and perhaps most importantly, the message needs to get out more widely that the brain, when impaired by ‘sticky blood’ can complain in a wide variety of ways, ranging from migraine through to memory loss and, yes, atypical multiple sclerosis.

* Tales of a flying doctor and the story behind Hughes syndrome is available from Hayward Medical Communications, tel: 0207 240 4493 or email: edit@hayward.co.uk

February 2011

Still cold and grey. Early March. I estimate that we’ve had eight hours of real sunlight this winter. No wonder vitamin D deficiency is rife. Vitamin D is, in fact, very fashionable. I used to regard vitamin D as ‘bones’. However, much recent research has suggested that vitamin D is also important in the protection given by the immune system – indeed recent evidence suggests that vitamin D deficiency is important in diseases such as lupus and Hughes Syndrome, where the immune system is disordered.

Last week, I travelled thousands of miles – to Oman and on to Japan. Two meetings, both, coincidentally, in honour of outstanding colleagues.

First to Oman – a beautiful and, until last week (!), a peaceful country – some say the original garden of Eden. Professor Nick Woodhouse, an old colleague and friend from thirty years ago, has spent most of his medical career in the Middle East – firstly in Iran, then in Saudi Arabia, and for the past twenty years or so, in the Sultan Qaboos University in Muscat, Oman, a glorious marbled palace of a campus, shimmering in the desert. Nick has been instrumental in linking western medicine with Oman, and has held regular annual postgraduate meetings there. This year, the 13th such meeting was his last – an outstanding three day event, with 300 keen young doctors, and a faculty of a dozen international experts.

As fate would have it, later in the same week, an almost identical celebratory event was held in Japan – in the northern town of Sapporo, where one of the world’s leaders in research into Hughes Syndrome – Professor Takao Koike, was holding a retirement one day meeting or ‘festschrift’.

I would not normally have travelled so far to a meeting, but for me, this was a special event – a very old friend, and a giant of medicine, was being honoured.

So, from the blue sky (it exists!) of Oman, via Dubai and Hong Kong, to snow-bound Sapporo. Two days there, then a twelve hour flight home from Tokyo. No more long haul, I hope, for some time.

During this epic voyage, just as with a similar long haul visit to Mexico two years ago, it was a joy to meet up with an old friend, Yehuda Shoenfeld, whose ideas and enthusiasm seem to marry with my own.

We plan to write a review attempting to highlight not only the importance of blood testing for antiphospholipid antibodies, but the shameful lack of such testing in present day health care.

Case of the Month

Mrs L R, a 37 year old actress, suffered a pregnancy loss at 34 weeks. Until then, the pregnancy had seemingly gone well, and routine pregnancy scans etc were all in order.

Mrs L R’s medical health was excellent, though a previous pregnancy had ended in miscarriage at four months. Some months following her late pregnancy loss, a more complete medical screen revealed an anticardiolipin (aCL) test as positive.

What is this patient teaching us?

Recently (and probably many times before), there have been a number of high profile newspaper reports of show-biz and other celebrities suffering tragic unexpected pregnancy losses.

While early miscarriage (usually in the first 12 weeks) is common, late pregnancy loss, as in the case of Mrs L R, is unusual – and very, very significantly is associated with Hughes Syndrome/APS. Medical experts are all agreed that any woman with late pregnancy loss – foetal death – should be tested for antiphospholipid antibodies (aPL). For the sake of a test costing a few dollars/pounds/euros, future pregnancy disasters could be prevented – with treatments as simple as aspirin and heparin.

And, in the case of Mrs L R, there had been an earlier miscarriage. Should she have been tested for aPL then? Statistically, arguably. Medically, definitely – her later tragic pregnancy loss could certainly have been prevented.

Hopefully, my colleague Professor Shoenfeld and I will put a strong (and passionate) case forward to the medical world arguing for more routine aPL testing in pregnancy.

January 2011

Wet, wet, wet! Cold, cold, cold! An unpleasant January. Semi-hibernation. Again, the kitchen floor covered in Lucy’s muddy paw-marks.

On Saturday 15th January, we held a GP postgraduate meeting. Something of an experiment for two reasons: firstly, on a Saturday morning, so soon after Christmas, we worried that we would have an empty room. And secondly, this was the first ‘Ten Topics in Rheumatology’ for GPs.

For the past 25 years we have held an annual two-day postgraduate rheumatology meeting at St Thomas’ Hospital. The formula of the ‘Ten Topics’ meeting is for short (15-20 minute) presentations by leading experts – presentations which are at the cutting edge of treatment and research. The meeting is run on a tight budget (£50 registration fee for doctors in training) and is limited by the size of the lecture theatre at St Thomas’ to 200.

So successful has the formula been that not only is the meeting fully subscribed, but ‘satellite’ Ten Topics are now held regularly in Barcelona, Rome, Buenos Aires, Singapore, Manilla, Hong Kong, Beirut and Nice – a successful medical ‘export’ from the UK.

This summer, we will be holding a very special ‘25th anniversary Ten Topics’ on 30th June and 1st July. If any of you have consultant or registrar friends who might be interested please email Sandy Hampson or visit the Ten Topics website.

And the January GP meeting? Amazingly, one hundred and sixteen GPs came to London for the morning’s programme. Ten 15-minute rheumatology topics, ranging from Hughes Syndrome, to lupus, to osteoporosis, to gout presented by the London Lupus Centre team. A big success – we certainly plan repeats; again I will give as much notice as possible, but do give the names of any of your doctors who might be interested to Sandy Hampson.

Finally, while on the subject of meetings, our annual patients’ forum is being held at St Thomas’ Hospital on Wednesday 25th May – please speak to Kate Hindle or visit the HSF website for more details on how to register.

Case of the Month

This is a patient I saw yesterday. I was asked by an orthopaedic colleague to see a 49 year old business man. He had been admitted for a hip replacement operation.

The history (at first) seemed straightforward. He was a keep-fit enthusiast, with gym exercises and jogging. Some six months earlier, he had started to complain of pain around the left hip. On examination, left hip joint movement was slightly limited by pain. An xray showed slight wear and tear, but a subsequent MRI scan was much more dramatic, showing extensive ‘softening’ of the head of the femur (a condition known as ‘avascular necrosis’, usually ascribed to an impairment of blood supply to that area).

With such an advanced stage of necrosis, there was only one real option. Hip replacement, which was carried out successfully. (Worryingly, the other ‘normal’ hip showed MRI signs of early avascular necrosis). The surgeons arranged for a series of tests – after all this was an unexpected event.

The past history of the patient was significant. A few years earlier, he had suffered two deep vein thromboses (DVTs) in the leg and, for a year, had been treated with warfarin.

There were no other features in the history (such as migraines) to suggest Hughes Syndrome – though he was concerned about recent memory loss.

The blood tests showed high titres of anticardiolipin antibodies (aCL).

What is this patient teaching us?

Previous ‘cases of the month’ have involved neurologists, obstetricians and cardiologists. We now know that orthopaedic surgeons can also see Hughes Syndrome. In the early 1980s, when we described the syndrome, we saw a number of cases presenting with hip (and sometimes other joint) necrosis. It has long been recognised that conditions causing blood sludging or clotting (such as sickle cell anaemia) can affect the blood supply to the head of the femur, and Hughes Syndrome is no exception.

Over the years, we have reported an increasing number of Hughes Syndrome patients with this complication. Even more interestingly, we have seen a number of patients who have developed foot bone (metatarsal) fractures – presumably on the basis of bone ischaemia. As yet, we don’t know how common these cases are or what proportion of the orthopaedic workload they represent.

The patient has been re-started on warfarin (in this case with an INR of 3). It will be interesting to see whether an improvement in blood circulation halts the disease progression in the other hip.

And the memory loss? The patient is booked for a brain MRI. I will keep you posted.

December 2010

There. It’s official. The coldest December since UK records began. The snow before Christmas was the deepest we have ever seen – and of course, everything stopped. Kent again cut off from London. At least it gave me the experience of an unusual journey to work. Trudging through the snow in my wellingtons, a lady must have taken pity on me. Her husband was coming to give her a lift. Would I like a lift? The next hour was spent in the back of a builder’s van, crawling and slipping towards London! Eternally grateful …

The headline in the Metro one morning in December was miscarriage link to risk of heart attack’. It quoted a study from Heidelberg, Germany, which had found a link between a history of miscarriages and later heart problems. No mention of mechanics.

For me, there was at least one possible link – antiphospholipid antibodies and untreated Hughes Syndrome.

We have known for nearly thirty years that if untreated, Hughes Syndrome can lead to both vein clots and, more seriously, to artery clots – for example, coronary thrombosis or stroke. And we also know that correct diagnosis and treatment can prevent these disasters.

It also, I strongly believe, supports the argument for the more routine testing for the antibody in miscarriage – and not just after three miscarriages – if only to pick out those women in whom prophylactic treatment (eg. with junior aspirin) might well make all the difference.

I know that this is something of a hobby-horse of mine, but I have aired these views in the January 2011 edition of the journal LUPUS.

This blog (including December’s case of the month) is rather serious for a piece written during the Christmas season. I apologise, but passionately believe that the message needs to get out to both the public and the population at large that here is a common and treatable condition. All that is needed is early diagnosis.

Case of the Month

Mrs D L, a 32 year old housewife, was referred down from Scotland by a haematology colleague who had diagnosed Hughes Syndrome.

Her history was interesting – and dramatic.

She was well as a child and as a teenager. No migraines and no major illnesses (her older sister and father were migraine sufferers). She became pregnant. Disaster. At eight months the foetus died.

Some three years later, and, interestingly, taking low dose aspirin, Mrs D L had a successful pregnancy, her daughter now a healthy seven year old. A year later she became pregnant a third time but miscarried at three months. No further pregnancies.

Six years later, she suffered a moderately severe headache and went to bed. The following morning she suddenly developed severe weakness in the left side of the body, and speech disturbance. A stroke. She was admitted to hospital where an MRI demonstrated a major cerebral infarct.

Over the following three months, she made a gradual but sustained improvement in strength, the speech returning to normal.

She was referred to a consultant in Glasgow who made the correct diagnosis, the investigations showing two abnormalities – a positive (medium strength) test for anticardiolipin antibodies, and a positive test for anti-Ro (one of the lupus tests).

What is this patient teaching us?

She has the antiphospholipid syndrome – with positive blood tests – albeit not strongly positive – a major artery brain clot, a history of late pregnancy loss, migraine.

Interestingly, one of the tests for lupus and related conditions – ‘anti-Ro’ - is also positive, supporting the diagnosis of autoimmune clotting disease.

Treatment options are clear. She needs immediate warfarin anticoagulation, keeping the ‘sticky blood’ thinner. Nobody, but nobody, needs another stroke.

A major lesson is the need to investigate (with simple blood tests for antiphospholipid antibodies) any woman with recurrent miscarriage – especially late pregnancy loss. Our patient from Scotland underlines this message so clearly.

One day – hopefully not too far away – patients such as Scottish Mrs D L will be tested, diagnosed, and treated correctly – and the risk of medical tragedies such as young peoples’ stroke, reduced.

November 2010

Cut off from London! November ended with a flourish. Snow and icy winds blowing down from the north. This morning (December 1st) the snow here in Kent is over a foot deep. Roads blocked. No trains to London. Joined a shivering band of doughty commuters on our local railway station platform. To no avail. All cancelled.

In forty years of commuting up to my hospital clinics in London, this is the first time we have been stranded. Still, it does mean that I can write my November blog – a day late. The start of advent – the marvellous chocolate advent calendar kindly given to our clinic by the German mother of one of our lupus patients. The countdown to Christmas – with no let up in our daily clinics.

Case of the Month

A 33 year old woman suffered a late pregnancy loss – seven and a half months into the pregnancy. There had been no prior warning of the tragedy. Her previous health had been good apart from the occasional migraine attack, but she had suffered one previous miscarriage at three months.

Blood tests after the pregnancy loss showed anticardiolipin antibodies (aCL) in moderately high titre.

What is this patient teaching us?

Two messages at least, one concerning diagnosis and one concerning blood tests.

In my view, this lady has Hughes Syndrome – the late pregnancy loss, past miscarriage, positive aCL test and migraine all point to the diagnosis. Yet she would not be classified as having the syndrome.

It is sometimes forgotten that diagnosis and ‘classification’ are different. Take the case of another disease – lupus. The American College of Rheumatology have drawn up a list of a dozen ‘criteria’ – a patient having four or more positive criteria being ‘classified’ as having lupus for inclusion, for example, in a research trial. But a patient with, say, a butterfly rash, nephritis and a strongly positive DNA test – clearly lupus – would not satisfy the criteria for entry into a study.

Likewise in Hughes Syndrome, classification criteria have been produced by a committee of doctors – useful for uniformity in international collaborative studies, but definitely not for diagnosis. Clear?

The second lesson from this sad case of the month concerns a hobby-horse of mine – aCL testing in pregnancy.

Although Hughes Syndrome is now recognised as the commonest, treatable cause of recurrent pregnancy loss, routine testing for aCL in pregnancy is still not carried out – indeed the current practice is only to recommend aCL testing after three consecutive miscarriages! The reason for this current practice, of course, is that there are many causes of early miscarriage, a common occurrence, and that aCL testing would not be cost effective.

And yet when a woman checks into our hospital pregnancy clinic, a series of tests is routinely carried out – including one for syphilis (how common a problem is that?).

My response is two-fold – firstly, if one of my family were to have a miscarriage, I would want to know the result of aCL testing – I most certainly would after a second one.

Tragically, late pregnancy loss – the death of a fully formed infant – can also be a feature of Hughes Syndrome. (Fortunately, they are a rare occurrence).

Could the tragedy have been prevented? With hindsight, of course, the answer would be yes. This patient had suffered a previous miscarriage. For the sake of a simple blood test (aCL) a future pregnancy could have been flagged up as ‘high risk’.

I suppose that as usual, it comes down to economics. Having said that, there have been a few cases of fetal loss recently in well-known people, including showbiz personalities, bringing much needed newspaper coverage to the subject. Perhaps the message will ultimately get across.

October 2010

Like London buses, medical conferences come in runs. Autumn is a particularly busy time for meetings and this year is no exception.

In early October I gave a lecture on the antiphospholipid syndrome to the Arabic Rheumatology meeting in Dubai. As it seems, all over the world, there is an increasing recognition of Hughes Syndrome in all aspects of clinical practice, from cardiology (angina), to ear, nose and throat (giddiness, balance problems) to orthopaedic (bone softening) to psychiatry (memory loss). The questions after each lecture and these meetings are seemingly endless. The Dubai meeting was on a Sunday, so the round trip was speedy (two days).

Incidentally, next year (30th June and 1st July 2011) will be our 25th ‘Ten Topics’ meeting, so we are planning a very special event. The conference, designed on a mixture of clinical and ‘basic science’, brief presentations, and focussing heavily on lupus and Hughes Syndrome, has proved extremely popular, and satellite ‘Ten Topics’ meeting are now held regularly in Spain, Italy, France, Argentina and the Far East. I will keep everyone posted in our Ten Topics website

Finally, on meetings and ‘spreading the word’ – in December (December 15th to be precise), we are holding an evening meeting for GPs at the London Bridge Hospital on two topics – lupus and Hughes Syndrome. If any of you have a GP who might be interested, please do contact Sandy Hampson on 0207 234 2155.

Case of the Month – ‘thirty years on’

Miss Joan R, then 18, presented to my clinic in 1980 (then at the Hammersmith Hospital) with a history of joint pains and fatigue. Her doctor tested her for lupus and rheumatoid arthritis, but apart from a positive ANA (anti nuclear antibody) test, all the tests were negative.

However, over the next few weeks, she developed headaches and grossly abnormal movements in the arms and legs. These were characteristic of chorea, better known as ‘St Vitus dance’. As well as the writhing ‘Thai dancer’ movements of the hands, there were involuntary head and neck movements.

One possible diagnosis was rheumatic fever, but tests showed no evidence for this (or for streptococcal infection).

At this time at Hammersmith, we were heavily into our research into antiphospholipid antibodies and their clinically associated features. We had seen a number of similar cases and, sure enough, Joan R tested strongly positive. Critically, brain MRI showed two small ‘dots’ and we elected to anticoagulate with warfarin.

Amazingly, the Chorea stopped. Almost overnight. Over the ensuing thirty years, Joan has remained well. A couple of attempts to stop warfarin resulted in a return of headaches and we quickly returned to medicine.

What is this patient teaching us?

Three lessons. Firstly, given correct diagnosis and treatment, the prognosis can be good. One of the questions I am always asked concerns the long term outlook. With a relatively ‘new’ condition, we don’t fully know, but cases such as Miss Joan R, then 18, now 48, do give us hope.

The second lesson concerns duration of treatment. As in other patients, attempts to stop anticoagulation treatment met with a return of symptoms – in Joan’s case, worrying headaches.

The third lesson concerns Chorea. St Vitus dance has long been recognised as a feature of rheumatic fever (a condition all but extinct in the United Kingdom), it is also (rarely) seen in lupus, in pregnancy, and in some women on the oral contraceptive pill. In retrospect, these cases may well have been individuals positive for antiphospholipid antibodies. Another example of the brain’s dislike of ‘sticky blood’.

The rapid response to warfarin begs the question …why? Permanent brain ischemia due to thrombosis would hardly have responded in this way. One possible explanation, though with no real proof as yet, is that some of the brain symptoms such as Chorea may be more down to the ‘sludging’ of the blood – impaired circulation – rather than full blown thrombosis or infarction. Possibly the newer brain scans such as PET and SPECT may help to answer such questions.

Footnote

One interesting talk I heard during busy October was from a Portuguese colleague (- and awareness of Hughes Syndrome is very high in Portugal and Spain). This doctor was reporting on an audit carried out by his team on the various antibody tests requested in his country – routine tests including ANA (anti nuclear antibody), anti DNA (for lupus), anticardiolipin (aCL) and rheumatoid factor.

And the most frequently requested test? aCL! My colleague, Dr Munther Khamashta, often reminds me that my colleagues (Dr Nigel Harris and Aziz Gharvi) and I should have patented the aCL test before we published it in the Lancet in 1983 – we would – he claims – have been millionaires with yachts in Cannes. Ah well …

September 2010

A few days late. My apologies. So different from last year’s glorious autumn. September was wet and dull. The kitchen floor is covered with Lucy’s muddy paw marks. In London, daily life made more difficult by frequent tube strikes. A number of my patients couldn’t make their appointments because of the disruption.

At London Bridge hospital, we have started a survey of the relevance of positive anticardiolipin tests in cardiology patients. We have a large cardiology department and we are in an ideal position to assess the possible contribution of ‘sticky blood’ to various cardiac symptoms such as angina and rhythm abnormalities.

One conference towards the end of the month – the biannual Anglo-French meeting, dealing largely with the two topics – lupus and Hughes Syndrome. The one day meeting was in Nice – the Brits are not alone with strikes – an air traffic controllers strike in France resulted in five of the speakers getting stuck en route.

From the lupus point of view, one of the ‘hot topics’ of the meeting was the advent of new drugs, notably Rituximab and Belimumab (most of the drugs end in ‘mab’, standing for monoclonal antibiotics). Although very new and very expensive, they are without doubt very promising – suppressing the so-called B-cells which produce the antibodies. A bit early at present for any experience in Hughes Syndrome, but watch this space. From a doctor’s point of view, it is great to have the major pharmaceuticals interested in our group of diseases at last. Hopefully, with their large research teams and enthusiasm, we will see real progress.

Flew back from Nice – azure sky, glittering sea, to Heathrow – torrential rain – first day of the Ryder Cup in Wales.

Patient of the month

A 57 year old housewife complained of increasing fatigue, aches and pains, sluggishness (both mentally and physically) and headaches. Her physician suspected an underactive thyroid and the blood tests confirmed his suspicions.

Further investigation showed a positive anti-nuclear antibody test. Lupus was considered but the main test for lupus (anti DNA) was negative. She was found to have dry eyes and mouth. The diagnosis was changed to Sjogrens Syndrome, and the very old-fashioned drug quinine (Plaquenil) was added.

Over the next six months, the aches and pains disappeared, but the headaches, and (to a lesser extent) the fatigue remained.

Further testing showed normal blood chemistry, a normal brain scan but a positive test for anticardiolipin antibodies (aCL). Baby aspirin (75mg) was started and, finally, the headaches and fatigue disappeared.

What is this patient teaching us?

Firstly, that there may be more than one diagnosis. Secondly, the triad of low thyroid, Sjogrens Syndrome and Hughes Syndrome commonly occur together. As these are classified as autoimmune diseases it is therefore not surprising that there should be overlap. (Anecdotally, it is also quite common for one or more of these conditions to be found in family members of our patients).

Each of the three conditions is helped by ‘natural’ and safe medicines – thyroid replacement, Plaquenil and aspirin. I often refer to the latter treatment as ‘two trees’ – aspirin from the willow tree and Plaquenil, a derivative of quinine, from the South American cinchona tree – allegedly chewed by native Indians years ago to treat fever!

August 2010

The rains came. Not in the biblical sense, but suddenly, in mid August, the sun disappeared and rain, wind and dreariness descended. A recent quote from the groundsman at Lord’s cricket ground: “we haven’t seen the sun for seventeen days!”

We were lucky during our holiday in coastal Kent. The rain held off for the Saturday evening on which Monica and I and the family had booked at an open-air opera performance of La Traviata. It was a wonderful evening in the grounds of Godington House – a magnificent pile, with lovely gardens, buried several miles from Canterbury in deepest Kent.

London, despite the weather, has been packed with tourists. The London Dungeon, opposite my hospital, London Bridge Hospital, has daily queues stretching for hundreds of yards each way. It adds to the bustle and colour of this part of London – though I’m not sure the ‘skeletons’ and ‘dead bodies’ scattered along the pavement outside our hospital do anything for the hospital’s reputation!

I suppose that for most people, August is the ‘quiet before the September storm’. It is certainly true in the world of medicine, September and October being the key months for lectures and meetings. More about those next month.

Patient of the month

Mrs T.B., a 37 year old hospital cook, had a life-long history of migraine. Between the ages of 5 and 15, her attacks had been almost monthly. They eased a little in her late teens and twenties, but returned with a vengeance in her thirties. There were some new features then, too. She complained of balance problems – generally mild, but occasionally more worrying. She also started to suffer occasional bouts of abdominal pain – thought to be ‘abdominal migraine’.

Her general health had otherwise been good apart from occasional bouts of asthma.

Her family history was significant with one sister with lupus, one aunt with rheumatoid arthritis and her mother and another aunt with thyroid problems.

She tested positive for antiphospholipid antibodies (aPL) and was treated with clopidogrel (Plavix) tablets. The migraine attacks have stopped. Totally.

What is this patient teaching us?

I make no apologies for coming back to the topic of migraine. It needs to be shouted from the roof tops that 1) migraine is a common feature of Hughes Syndrome and 2) treatment of Hughes Syndrome (with aspirin, Plavix, heparin or warfarin) often results in improvement – sometimes the abolition of the migraine.

What led to this patient’s successful treatment? Firstly, the family history of autoimmune diseases (lupus, rheumatoid arthritis and thyroid disease) led to a heightened suspicion of the diagnosis, and the testing for aPL by her physician.

Normally, the first line of treatment might be aspirin. However, Mrs T.B. suffered from asthma – usually a contra-indication to aspirin. The alternative to aspirin in this situation is a tablet called clopidogrel (the trade name in the UK is Plavix). This agent, similar to aspirin but with less stomach irritation, is widely used in cardiology. I am increasingly using it in some of my Hughes Syndrome patients and am impressed with the results in quite a number of those patients with migraine.

Finally, there may be another significant spin-off from this observation. It has long been recognised that occasional migraine patients suffer from stroke. Obviously, it is quite possible that the antiphospholipid syndrome might be the missing link in some patients.

I hope the next couple of years will see the publication of studies from around the world addressing these questions.

The simple observation that a drug as simple as aspirin or Plavix can bring relief to some cases of migraine could just lead to bigger medical rewards, both for the patients and for the medical world at large.

July 2010

Yes, the good weather lasted and our Ten Topics meeting went well. And the air conditioning worked!

Our annual St Thomas’ two-day medical meeting was possibly the best ever. Two hundred attendees from eleven countries (including America and Japan). New data on Hughes Syndrome – the hopes for new warfarin alternatives getting stronger, and more details on the mechanisms behind the increased clotting seen in the syndrome. In the parallel world of lupus, the excitement of new drugs such as rituximab and belimumab, and the worldwide increase in awareness of lupus as a common and important disease.

Each year we also invite one (or two) ‘V.I.P’ speakers. This year was the turn of Dr Ed Coats, who gave a thrilling account of his epic journey to the South Pole with Ben Fogle and James Cracknell, filmed for television. The other was Dr Richard Horton, Editor of Lancet, who gave a brilliant overview of the strengths and weaknesses of scientific journalism. It is no wonder that the Lancet’s star shines so brightly.

July has been sunny, hot and dry – indeed, in our area in North West Kent there has been only one rain shower all month. Our town seems to have an ecosystem of its own – one of the driest spots in Britain. Our miniature Schnauzer puppy, Lucy, seems to thrive on the desert conditions in our garden, her moustache full of straw and twiglets.

Finally, many of you will know that Kate Hindle, who runs our charity, has been ill and off work for the past month. Get well soon, Kate.

Patient of the month

Mrs J.L.’s G.P. phoned to say that his patient’s latest blood tests showed a falling platelet count – the last figure being 90,000 (normal 130 – 400 thousand). Apart from slight bruising, she was very well – on warfarin.

Her past history was striking. As a teenager she had been admitted to hospital with low platelets – a count of less than 10,000) and diagnosed as having ‘ITP’ (idiopathic thrombocytopenic purpura), the word ‘idiopathic’ meaning that other known causes such as lupus had been excluded.

She was treated with a course of steroids and responded well.

Some ten years later, she suffered two miscarriages followed by increasingly severe headaches, culminating in a ‘TIA’ (transient ischaemic attack, or ‘mini’ stroke). MRI at that time was normal, but some months later she again suffered a probable stroke accompanied by loss of half of her field of vision. At this time the MRI showed definite abnormalities. She was also found to have positive antiphospholipid antibodies, diagnosed as having Hughes Syndrome, and started on warfarin.

And for the following nine years she remained well…., until now, at the age of 38 when she was found to have a reduced platelet count.

What is this patient teaching us?

Certainly the warfarin has been ‘life-saving’ with no progression of headaches or stroke for nine years.

On examination, she was unable to see out of the left half of her visual field – a defect pinpointing the previous stroke precisely to the right posterior (occipital) brain cortex. No doubt about the seriousness of her disease and the necessity for warfarin.

But what about the low platelets? Very low platelet counts can result in dangerous bleeding – indeed, Hughes Syndrome is one of the few situations that can perversely lead both to clotting and to bleeding. Treatment of low platelets is generally with steroids (or in more resistant cases, with globulin) – fortunately this patient’s platelet count at 90,000 is not dangerous, and no new treatment is required. Watch and wait.

For the researchers, this patient’s history again serves to link blood platelets with the tendency to blood clots in this situation. In retrospect, her teenage ‘ITP’ was certainly a manifestation of Hughes Syndrome.

Most telling of all, it highlights the link between positive antiphospholipid antibodies and stroke, something that needs shouting from the roof-tops.

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