Lower urinary tract symptoms (LUTS) are a common complaint in adult men with a major impact on quality-of-life and substantial economic burden.
The present EAU Non-neurogenic Male LUTS Guidelines are symptom-orientated and offer practical evidence-based guidance on the assessment and treatment of men aged 40 years or older with various non-neurogenic benign forms of LUTS.
The understanding of the LUT as a functional unit, and the multifactorial aetiology of associated symptoms, means that LUTS now constitute the main focus, rather than the former emphasis on benign prostatic hyperplasia (BPH), and secondary to benign prostatic obstruction (BPO), detrusor overactivity (DO)/overactive bladder (OAB), or nocturnal polyuria in men over 40 years.
The high prevalence and the underlying multifactorial pathophysiology of male LUTS mean that an accurate assessment of LUTS is critical to provide best evidence-based care.
A practical algorithm has been developed by the EAU for guidance (see Figure 2).
LUTS management (summary)
Conservative and pharmacological treatment
Watchful waiting is suitable for mild-to-moderate uncomplicated LUTS. It includes education, reassurance, lifestyle advice, and periodic monitoring.
First choice of therapy is behavioural modification, with or without pharmacological treatment. A flow chart illustrating conservative and pharmacological treatment choices according to evidence-based medicine and patients’ profiles is provided in the guidelines.
Prostate surgery is usually required when patients have experienced recurrent or refractory urinary retention, overflow incontinence, recurrent urinary tract infections, bladder stones or diverticula, treatment-resistant macroscopic haematuria due to BPH/BPE, or dilatation of the upper urinary tract due to BPO, with or without renal insufficiency (absolute operation indications, need for surgery). Surgery is usually needed when patients have had insufficient relief in LUTS or post-void residual after conservative or pharmacological treatments (relative operation indications).
The choice of the surgical technique depends on prostate size, comorbidities, ability to undergo anaesthesia, patient’s preference/willingness to accept surgery-associated side effects, etc.
In relation to the management of nocturia in male LUTS patients, the guidelines state that assessment must establish whether the patient has polyuria, LUTS, sleep disorder or a combination. Therapy may be driven by the bother it causes, but non-bothersome nocturia may warrant assessment of a frequency volume chart (FVC), depending on history and clinical examination, since potential presence of a serious underlying medical condition must be considered.
EAU guidelines recommended male LUTS patients follow-up strategy:
Patients with watchful waiting should be reviewed at six months and then annually, provided symptoms do not deteriorate or absolute indications develop for surgical treatment.
Patients receiving beta-1-blockers, muscarinic receptor antagonists, beta-3 agonists, phosphodiesterase-5 inhibitors, or a combination should be reviewed four-to-six weeks after drug initiation. If patients gain symptomatic relief without troublesome side-effects, drug therapy may be continued. Patients should be reviewed at six months and then annually, provided symptoms do not deteriorate or absolute indications develop for surgical treatment.
Patients receiving 5α-reductase inhibitors should be reviewed after 12 weeks and six months to determine their response and adverse events.
Patients receiving desmopressin: Serum sodium concentration should be measured at day three and seven and after one month and, if serum sodium concentration has remained normal, every three months subsequently; the follow-up sequence should be restarted after dose escalation.
Patients after prostate surgery should be reviewed four-to-six weeks after catheter removal to evaluate treatment response and side effects. If patients have symptomatic relief and there are no side effects, further assessment is not necessary.
The Non-neurogenic Male LUTS Guidelines can be accessed at the EAU website at http://www.uroweb.org/guideline/treatment-of-non-neurogenic-male-luts/.
Urinary incontinence is largely a ‘hidden’ condition. Patients do not readily admit to symptoms and some doctors are still to this day unaware of their prevalence. Within the general population, up to 19 per cent of children and at least 20 per cent of women and 10 per cent of men may be affected by some form of urinary incontinence.
It is estimated that about one-third of the population in Ireland is affected by one or more of the different aspects of incontinence, with the incidence increasing with age, and an estimated 350,000 people over the age of 40 years are affected with overactive bladder (OAB) alone.
The term ‘urinary incontinence’ refers to the complaint of any involuntary loss of urine. Urinary incontinence can be categorised into several distinct subtypes based on associated characteristics and circumstances surrounding episodes of urine leakage. Although defining the type of incontinence will not establish a definitive underlying diagnosis, it will ultimately guide investigation and treatment (see Table 1).
Initial assessment of urinary incontinence
Patients with urinary incontinence can be identified through routine screening, or if the patient initiates a discussion about their urinary symptoms. The initial assessment should help with understanding the type of incontinence, while identifying potentially modifiable contributing factors. Most primary treatment options, such as lifestyle modifications and behavioural treatments, are the same for different types of incontinence.
Should include questions in relation to aggravating factors of urinary loss, onset, duration of symptoms, and degree of bother. Acute symptoms can be related to patterns of fluid intake and output, acute urinary tract infection, or recent surgery or trauma. Chronic symptoms should prompt queries about a history of congenital abnormalities, neurological disease, relevant surgery or general health. A detailed history of medications with known or possible effects on the lower urinary tract should also be obtained.
Use of questionnaires may help with disclosure of embarrassing symptoms and ensure that symptoms are not omitted. In the absence of a questionnaire, we would recommend the use of a standardised table of questions (see Table 2).
A bladder diary is recommended in order to document and communicate objective information and observations by the patient during the diary period. Despite the fact that diaries are never completely diagnostic, they may demonstrate both normal and abnormal patterns.
The ideal duration of a bladder diary is not yet clear; the recommended duration is three days for accurate assessment of lower urinary tract symptoms (LUTS). However, a seven-day diary is recommended in atypical clinical patterns.
It is considered standard to do a urinalysis by either a dipstick or sending a mid-stream urine sample at each visit to the clinic.
Secondary investigations include urodynamic testing, a cystoscopy, and imaging of the upper urinary tract. These should be considered in patients with neurological disease, refractory OAB, or those in whom initial investigations raise the suspicion of an underlying problem that may require further evaluation or treatment.
Treatment of OAB
This involves maintaining an adequate intake of 1.5-to-2 litres of fluid per day (six-to-eight cups), decreasing evening fluid intake, in particular when there is nocturia. An important part of this is reducing caffeine intake, present in coffee, tea and green tea, and also reducing other types of fluid that cause irritation to the bladder, such as alcohol, carbonated drinks, citrus, tomato, and spicy food.
Weight loss has been proven to improve both stress and urge incontinence, and it is also recommended to quit smoking and avoid constipation by increasing dietary fibres.
Pelvic floor exercises
These are aimed at strengthening the pelvic floor musculature. The rehabilitation programmes may include simple oral or written information, exercises performed with biofeedback, pelvic muscle contractions stimulated by functional electrical stimulation (FES), motor relearning exercises, or any combination of the above. Success is dependent on a continuous, regular home exercise programme to avoid deconditioning. Pelvic floor muscle training can also help improve prolapse symptoms and severity. They can also help improve quality-of-life prior to surgery.
The target is increasing the voiding interval and decreasing urgency and associated urge incontinence. The three components to the training are patient education, scheduled voiding, and positive reinforcement.
This should be undertaken in small steps. For example, if the patient is going to the toilet every half an hour, they should try extending the time (or ‘holding on’) by 10 minutes for a week, then by 15 minutes for a week, and then 30 minutes, etc. The aim is to eventually be able to hold on for three-to-four hours between toilet visits.
There are many options of anticholinergic medications to choose from, which are demonstrated in Table 3.
Another relatively new drug used is mirabegron, which is a β3-adrenoreceptor agonist, and because its receptors are more specific to the bladder, it has fewer side-effects. It is considered as a second-line therapy when patients are intolerant to anticholinergics.
The choice of anticholinergic therapy should be guided by individual patient comorbidities, as objective efficacy of anticholinergic drugs is similar.
Absolute contraindications to anticholinergic use include urinary retention, gastric retention, uncontrolled narrow-angle glaucoma, and known hypersensitivity to the individual drugs or any of their ingredients.
Elderly patients in particular should be monitored for drug interactions or polypharmacy of drugs with anticholinergic effects (ie, antidepressants, antipsychotics, anxiolytics), as the overall anticholinergic load is associated with confusion, falls and fractures. Anticholinergics are category C drugs in pregnancy, to be used only if the benefits clearly outweigh the risk.
Intravesical botox injections
Intravesical botulinum toxin A prevents acetylcholine release at the neuromuscular junction, resulting in temporary chemodenervation and muscle relaxation for up to six months. The usual technique is using 100IU of botulinum toxin diluted in 20ml of normal saline, and then injected into a non-trigonal area of the bladder wall in 20 different places.
Complete continence can be achieved in 40-to-80 per cent of patients and bladder capacity improves by 56 per cent for up to six months. Maximal benefit is between two and six weeks, maintained over six months. The injections can be repeated according to degree of improvement or relief of symptoms.
It is important to teach the patient how to do intermittent self-catheterisation beforehand, as the risk for the development of urinary retention is between 10-to-15 per cent.
Other treatment modalities
Other options also include posterior tibial nerve stimulation and sacral nerve stimulation, which involves an implantable electrode in the S3 foramen continuously stimulating the S3 nerve root, in order to stimulate the pudendal nerve. There is a potential benefit for up to five years in patients with OAB.
Some more radical methods of treatment include augmentation cystoplasty and urinary diversion. Indications for bladder augmentation include a small, contracted bladder and a dysfunctional bladder with poor compliance. Urinary diversion should be considered only when conservative treatments have failed, and if sacral nerve stimulation and augmentation cystoplasty are not appropriate or unacceptable to the patient.
Management of stress urinary incontinence
Pelvic floor exercises
Pelvic floor muscle training is considered the first-line treatment for urinary incontinence and aims to strengthen the levator ani and pubococcygeal muscles, which affect the urethral closure mechanism.
Today, there is a huge body of evidence from randomised, controlled trials and systematic reviews concluding that pelvic floor muscle training is effective in the treatment of stress incontinence. Several systematic reviews have recommended conservative treatment and especially pelvic floor muscle training as first-line treatment.
However, many surgeons seem to regard minimally-invasive surgery a better first-line option than pelvic floor muscle training. The scepticism against pelvic floor muscle training may be based on inappropriate knowledge of exercise science and physiotherapy, beliefs that there is still insufficient evidence for the effect of pelvic floor muscle training, that evidence for long-term efficacy is lacking or poor, and that women are not motivated to regularly perform pelvic floor muscle training.
An incontinence pessary is a silicone ring device with a knob placed in the vagina, with the goal of stabilising the urethra to eliminate hypermobility and increase urethral pressure during increases in intra-abdominal pressure. This is a safe and effective conservative treatment.
Periurethral bulking agents
Periurethral bulking injections are performed via the urethral route using a cystoscope, and demonstrate highly variable success rates ranging between 26 per cent and 75 per cent.
A wide variety of material can be used; most commonly used is Bulkamid, which is a homogenous hydrophilic gel consisting of 2.5 per cent polyacrylamide and 97.5 per cent water. Bulkamid appears to be a relatively safe and minimally-invasive means of narrowing the lumen of the urethra. It seems to have a positive effect for at least six months to two years, and it is possible to re-inject patients. No material has proved better than another. This appears to be a good option for older, unfit patients, or those who have failed other incontinence treatments.
Through the years, hundreds of different surgical options have been developed for the management of stress incontinence, but nowadays, midurethral slings utilising synthetic mesh remain the gold standard.
The retropubic tension-free vaginal tape sling (TVT) was the first to be introduced. It was developed based on the theory that the tape should substitute the pubourethral ligament that is responsible for the support of the mid-urethra. There is a small risk of perforating the bladder while inserting a TVT, which can be assessed by doing a cystoscopy.
Later on in 2001, the transobturator tape (TOT) sling approach was introduced with the hope of avoiding vascular, bladder, and bowel injuries. TOT sling trocars traverse the obturator canal instead of the retropubic space and enter through small groin incisions at the level of the clitoris bilaterally.
Mesh complications from midurethral slings are uncommon and are reported to be less than 4 per cent but can include mesh erosions into the bladder or urethra, mesh exposures in the vagina, pain, dyspareunia, and rare complications, such as severe infections.
See www.continence.ie for more information and resources.
Being able to effectively obtain and use health information is an essential element of empowering and supporting patients to self-manage their chronic conditions. Supporting people to self-manage their health conditions through systematic provision of education and supportive interventions increases their skills and confidence and improves outcomes for patients – ranging from quality-of-life and clinical outcomes, to reduced healthcare utilisation including hospitalisation.
The Migraine Association of Ireland (MAI) is Ireland’s only patient organisation for people suffering from migraine and other headache disorders. It is estimated that over 500,000 people suffer from migraine in Ireland. While 14-15 per cent of these people are chronic migraine patients (more than 15 days migraine per month) and will require specialist treatment and preventative medications, most migraine sufferers experience episodic attacks. Episodic migraine attacks can be effectively reduced and managed with lifestyle and dietary adaptations. Learning to identify triggers is a key element of an effective migraine management programme.
Self-education and self-management can also prevent an over-reliance on over-the-counter medications, which can give rise to medication overuse headache. In 2011, the Dublin Neurological Institute undertook an audit of patients attending their specialist migraine clinic and they found that medication overuse headache was present in 52 per cent of patients attending the clinic.
Education and self-management supports
The MAI provides a number of free seminars for migraine sufferers throughout the year covering a variety of themes from ‘Hormonal Migraines in Women’, ‘Migraine in Children and Teens’ to general migraine seminars helping people better understand their condition. We also run a self-management course, over three weeks, one evening a week and during this course patients are connected with medical experts from the national migraine clinics to receive specialist training and advice on their condition. The course also equips people with the skills and strategies to better manage their condition. Modules include the migraine friendly diet, supplements for migraine prevention, identifying triggers, exercise and stress reduction techniques. We have also incorporated cognitive behavioural therapy (CBT) techniques in our programme so we can help people accept that migraine is a neurological condition they may always have and to adapt their expectations and lifestyle choices around the condition rather than always searching for a cure.
If GPs have patients who are suffering regular migraines, a referral to the MAI can be a positive first step in achieving better patient outcomes. The MAI also operates an information and support line that patients can call for support and advice and through this they can also be referred to a specialist migraine nurse.
Another key challenge for migraine sufferers internationally is that migraine remains undiagnosed and undertreated in at least 50 per cent of patients. On average migraine sufferers are taking six-to-seven years to receive a proper diagnosis of migraine.
Irish GPs currently only receive four hours training in headache as part of their undergraduate training. This is despite the fact that migraine is the most common primary headache seen by GPs. Three-quarters of the patients presenting to the Migraine Clinic at the Dublin Neurological Institute in the Mater Hospital, Dublin, have never been prescribed a preventative therapy, which indicates there is a serious lack of knowledge about chronic migraine in the primary care setting.
Resources for healthcare professionals
The MAI in recognition of this challenge provides a number of specialist health professional training seminars, for GPs and other healthcare professionals throughout the year. We have been in existence for nearly 25 years and through our network of contacts at a national and international level we have the ability to attract a high calibre of headache and migraine experts. The events are free to attend and carry RCPI and NMBI CPD points. We also have a comprehensive health professional section on our website, www.migraine.ie, which provides in depth diagnostic materials and resources. The patient section of our website is also a good referral tool for GPs to direct migraine patients to so they can better understand their condition.
You can email or contact the MAI on firstname.lastname@example.org or 01 894 1280. The MAI Information and Support Line operates Monday to Friday 10-4 pm and the number is 1850 200 378.
Our book Migraine Not Just Another Headache is also available to buy from local bookshops and from our website.
Written by experts, this book describes the role of the GP, nurse, pharmacist, paediatrician, physiotherapist and psychologist in the treatment of migraine. It advises about the management of migraine in the home, at school, in the sports centre and workplace. It gives crucial information from neurology and from specialist migraine clinics about pain management, migraine in children and adolescents, and the legislation to support people in educational and employment contexts.
The Migraine Association of Ireland hosted a health professional education seminar in Dublin last month, which offered attendees the opportunity to acquaint themselves with current and emerging therapies applied in the management and treatment of migraine and featured presentations from two of the world’s leading migraine and headache experts – Dr Lars Edvinsson and Dr Allan Purdy.
Dr Edvinsson was the main researcher in the discovery and development of the new Calcitonin Gene Related Peptide (CGRP) antibodies and is a Neurologist at the Department of Emergency and Internal Medicine, Skåne University Hospital and Professor of Internal medicine at Lund University in Sweden. He is chairman of the Swedish Migraine Society and the current President of the International Headache Society.
Recently retired Dr Purdy was a Neurologist and Professor in the School of Medicine at Dalhousie University in Nova Scotia, Canada. He is the immediate Past President of the American Headache Society and has also served as President of the Canadian Headache Society and on the Board of Directors of the International Headache Society.
In his opening remarks to the meeting, Mr Patrick Little, CEO of the Association, noted that GPs and medical students receive very little training in migraine and he detailed the work of the Association in helping provide high quality education for clinicians on the topic in order to optimise the management of migraine patients in Ireland.
The development of CRGP
Dr Edvinsson recounted the early steps and milestones in the understanding of the neuropeptide CGRP in the trigeminovascular system and its role in migraine and the journey to develop blockers of CGRP effects.
Essentially, CGRP is released into the blood stream during a migraine attack and has a central role in the underlying mechanisms of a migraine attack. It is known to cause blood vessels to dilate and cause inflammation at nerve endings.
His groundbreaking work on the sensory system has now resulted in the development of new migraine therapies, including small molecular CGRP-blockers for acute attacks and antibodies towards CGRP or CGRP-receptors as prophylaxis for chronic migraine.
Recent results from clinical trials on monoclonal antibodies targeting CGRP are encouraging (one study found 50 per cent of those given the antibody injections halved their number of migraine days per month) with the EU Commission recently granting a marketing authorisation for the first drugs (Erenumab and galcanezumab) in the EU. Both are primarily prescribed for the prevention of migraine in adults with chronic refractory migraine and it is hoped they will be available in Ireland in the next year.
Speaking to the Medical Independent (MI), Dr Edvinsson said it was an exciting time with the new class of drugs on the verge of becoming widely available for migraine patients in Europe.
He acknowledged the long gestation period and delays in their development was somewhat frustrating, but he believes they will have a dramatic impact on the prophylaxis and treatment landscape for migraine patients; “they will with certainty”.
Diagnosing and treating migraine
Dr Purdy gave an engaging overview of the different migraine types, diagnosis and treatment options and ‘pearls of wisdom’ on treating this headache disorder, which “while it seems straightforward it is anything but and anyone who has to deal with migraine patients recognises it is very complex”.
Dr Purdy emphasised that listening to the patient and having that knowledge of their individual experiences and reactions to various therapies remains the key to successful management: “Even though there have been tremendous advances in the science of migraine and understanding of the pathophysiology and that it is a true neurological disorder and the new and exciting advances detailed by Dr Edvinsson, if you really see what is going on in the world of migraine this still becomes the cardinal interaction with the patient.”
He noted the third edition of the International Headache Society (IHS) International Classification of Headache Disorders (ICHD-3) is a useful tool for clinicians dealing with migraine patients.
Looking at the presentation and diagnosis of various types of migraine, Dr Purdy commented that “migraine hijacks all of the brain” and “you should think everything is migraine until it isn’t”.
However, he also stressed the importance of thorough diagnosis and investigation of red flags noting that migraine can mimic many other issues such as a brain tumour.
When correctly diagnosed the basis of traditional migraine treatment remains reducing attack frequency and eliminating acute-attack symptoms: “So acute therapy, preventative therapy and behavioural therapy. But then you also have to manage the co-morbid disorders that go along with migraine as these will determine disease progression. And migraine is a disease; it is not simply a disorder…”
He stressed the importance of asking patients what they want treatment to ideally achieve, and recognising the specific risk factors of which treatments are prescribed for which patient, ie, if the patient is female, smokes, is aged over 35, is obese, etc.
Summarising the data on triptans to date (Lancet meta-analysis), Dr Purdy said all oral triptans are well tolerated, none are demonstrably safer than the others and at marketed doses all are effective and well-tolerated.
“The secret is that patients are more different than individual triptans” so trial and error is part and parcel of finding the best one for individual patients, Dr Purdy stated.
Discussing the various preventative therapies (betablockers, anti-epileptics, antidepressants, NSAIDs, calcium channel blockers, etc), he acknowledged that they are underused in general though efficacy can be mixed/disappointing. They also present issues with compliance – patients want them to be effective, not to have side effects and be easy to take, while knowing how long to take them is an issue and patients can stop taking them when their migraine occurrence reduces and then relapse.
Looking at the newer medical devices and alternative treatments, he said there is some promise in neuromodulation, but many devices are overhyped and ineffective. However, he expressed optimism about the forthcoming CGRP-related therapies, which could make a significant impact for patients and address a previously unmet need.
Speaking to MI after his presentation, Dr Purdy reiterated the importance of all doctors, particularly primary care physicians, having a good knowledge of migraine.
“If I was a physician in this era, the 21 century, I’d get very interested in migraine and the reason being that migraine tells you how the brain works. Every time a patient tells you a symptom, they are telling you how the brain works and exactly what is going on and that is fascinating. There are very few other disorders that I can think of that explore how the human behaviour and condition is affected by this very unique neuro-biological disorder.”
He said taking the time to listen to the patient and taking a thorough history and detailing of their symptoms is absolutely key, and this can take an hour or two: “The real secret is to nail the diagnosis and if you can’t do it in 10-15 minutes, bring them back three or four times, which adds up to an hour. Because if the diagnosis is incorrect everything else from there is downhill. But if it is absolutely pristine or the best you can do then there are really good options to treat migraine and they are getting better.”
Dr Purdy acknowledged that many doctors lack adequate knowledge of migraine and the best treatment approaches and prefer to refer to a specialist but he said most patients can be well managed in the community.
“A lot of doctors manage the patients very well, but a lot don’t want to manage them… It takes time and effort. But you have to understand that if you get a migraine patient and you spend the time with them and you train them to learn these things [prevention and management strategies] you can get a win; in other words you’ll make them better and you will hopefully prevent them for getting into these patterns later in life.
“That might be too hopeful, but it’s not cynical to say that I spent a lot of time in my 40-year career, which has just ended clinically, seeing new patients because I thought they could be helped and I spent a lot of time seeing chronic ones because that is what we do as neurologists, so what I’m saying is learn about migraine – learn all about it, go to some meetings, spend some time with them [migraine patients] and get to know your local neurologist and call them up and ask ‘what can I do’.
“I think education is the key here.”
The Irish Society for Rheumatology (ISR) Autumn Meeting 2018 takes place on 19-21 September in the Killashee Hotel, Naas, Co Kildare.
According to ISR President Dr Sinead Harney, Consultant Rheumatologist at Cork University Hospital (CUH), the meeting agenda is “really varied” and there is “something for everyone”.
“I think it will be good,” Dr Harney told the Medical Independent (MI).
“The programme is exciting. It is an international programme and the reason we can get international speakers is the generosity of all industry, so we are always grateful for that. And the attendance is always very high, and the role of the allied health professionals — the fact we are tight with them — is good as well. We are looking forward to it.”
Dr Sinead Harney, ISR President
Among the highlights will be a presentation by Prof Dirk Elewaut, Consultant Rheumatologist, Ghent University, Belgium, who will speak on ‘The gut in spondyloarthritis vs the joint in inflammatory bowel disease: Two sides of the same coin?’, while Dr Ian Giles, Consultant Rheumatologist, University College Hospital, London, UK, will discuss the topic ‘Optimising the management of women of child-bearing potential living with rheumatic disease’.
“A lot of our patients are women aged between 30 and 45-50; it is an important time in their life and a lot of our drugs can be used safely [in pregnancy] so [Dr Giles] is going to speak on this area,” noted Dr Harney.
Prof Luke O’Neill, Professor of Biochemistry in the School of Biochemistry and Immunology, Trinity College Dublin (TCD), will deliver a presentation titled ‘Krebs Cycle reprogrammed for cytokines: New therapeutic options for inflammatory diseases?’
Prof O’Neill is “always really good”, said Dr Harney, “and he brings immunology back to basics”.
Another eagerly-anticipated presentation will be that of Prof Lihi Eder, Professor of Rheumatology, University of Toronto, Canada, who will speak on cardio-metabolic diseases in psoriatic arthritis.
Rheumatology Patient Initiative Fund (RPIF)
One of the important facets of the meeting will be presentations by winners of the Rheumatology Patient Initiative Fund (RPIF).
The RPIF is intended for innovative researchers undertaking a body of research in rheumatology in Ireland that will directly impact on patient care and quality-of-life.
According to Dr Harney, five winners will present their research. This initiative is particularly important, as it supports basic clinical research that will impact on patients and it has been made possible by an educational grant from UCB, outlined Dr Harney.
The meeting will also feature the presentation of the Bernard Connor Medal 2018, which is aimed at encouraging medical student participation in rheumatology during their undergraduate education and supporting student engagement with the activities of the ISR.
The medal is named in honour of Dr Bernard Connor, an Irish physician who observed and described the characteristic skeletal and clinical features of ankylosing spondylitis in 1693, while himself a medical student in Paris.
Funding, manpower and infrastructural constraints affecting the specialty will not be far from delegates’ thoughts, according to Dr Harney.
Dr Tim Jones, Associate Lecturer at Oxford Brookes University, UK, will be presenting on building a business case for funding, and Dr Harney expects that this will be useful for delegates.
She said rheumatology has been “grossly under-funded in respect of consultants and infrastructure for the last 20 years”.
Dr Harney underlined that “we are always fighting for funding and we are grossly under-funded”.
“As President [I can say], we are all a bit demoralised, in that we need more consultants to keep pace with the workload…. also, the fact that general medicine over-impacts on our week. I spend more than 50 per cent of my week doing general medicine, so although there are 2.8 of us, there are actually only 1.4 here for this end of the country, in our department [at CUH],” said Dr Harney.
Levels of infrastructure vary across units, according to Dr Harney, who considered Cork as “probably the worst part of the country” in this respect.
At CUH, she said, lack of infrastructure to undertake day cases is causing huge problems in respect of patient care.
“In CUH, we have a prefab that was funded by industry and other than that, we have no physical footprint in the hospital,” she stated.
Insofar as possible, patients with private health insurance who have been attending CUH and require infusions have been referred to private hospitals in the area, she outlined.
“But our public patients are waiting for up to nine months to get an infusion,” said Dr Harney, adding that this care should be accessed within six months. “We are now stretching out to nine months of the year for six-month infusions, so we are on the verge of clinical risk and potentially leaving ourselves open to risk.”
These service deficits are impacting on retention of trainees, as is the new-entrant consultant salary.
“Some who have gone to the UK who I thought would come back, haven’t, for that reason [of new-entrant salary]. And then, they see how hard we have to work just to get slots for our patients to come in, and we do have to admit people overnight. We wasted 100 bed days here last year by having to admit people because we couldn’t get them day beds, so the lack of day beds is critical in CUH.”
Dr Harney said one of the helpful developments achieved through the National Clinical Programme for Rheumatology in recent years has been access to physiotherapists to undertake back pain clinics. But there remain many areas for improvement in respect of resourcing, she underlined.
Meanwhile, there will be a number of industry-supported satellite events on topical issues at the meeting, namely the MSD Satellite Meeting, where Consultant Gastroenterologist Dr Anthony O’Connor, Consultant Rheumatologist Prof Trevor Duffy and Senior Research Fellow in Psychology at TCD Dr Derek Richards will discuss the topic of ‘Identifying and managing mental health symptoms in patients with chronic disease’; the Novartis Satellite Meeting, where Prof Peter Nash, University of Queensland, Australia, will provide an update on IL-17a in spondyloarthritis; and the AbbVie Satellite Meeting, where Prof Lihi Eder of the University of Toronto will deliver a presentation titled ‘From psoriasis to psoriatic arthritis — can we improve early detection?’
ISR: Driving the specialty forward
The Irish Society for Rheumatology (ISR) is an organisation of about 150 members with specialist training in rheumatology. Members include consultants, trainees, scientists and researchers. The Society includes those who are based in the Republic of Ireland, Northern Ireland, the rest of the UK and some from further afield.
The ISR is a registered charity that organises and hosts regular platforms and conferences allowing members to present clinical and scientific material. It also promotes ongoing education and training in rheumatology at all levels and, in particular, in the postgraduate areas of professional training and higher medical training.
International links are maintained and developed to assist with the flow of information in the field. Currently, the Society enjoys links with a number of international bodies, including the American College for Rheumatology (ACR), the British Society for Rheumatology (BSR) and the European League against Rheumatism (EULAR).
For further information, visit www.isr.ie.
Dysphagia is one of the many complications of stroke and approximately 10,000 people in Ireland have a stroke-related event annually. Furthermore, an estimated 30,000 people are living in the community with disabilities as a result of a stroke.
It is also a frequent symptom in frail, older people or in individuals with any impairment of oral structure, or their respiratory or neurological systems, and is observed in a large proportion of people with dementia. It can also occur in patients with Chronic Obstructive Pulmonary Disease (COPD) and those with head and neck cancers.
Dysphagia refers to the sensation of not being able to swallow, food ‘sticking’ or not passing, choking episodes, or aspiration of food and/or liquids. It can also affect a patient’s ability to take medication and therefore can result in practices such as crushing and/or mixing, which can adversely affect the pharmacodynamics of the drug.
Dysphagia is also a strong predictor of malnutrition risk and dysphagic stroke patients are 2.4 times more likely to be malnourished compared with those who have normal swallowing function.
According to the Irish Heart Foundation, one-in-five people will have a stroke at some time in their life and approximately 50 per cent of people who have a stroke have swallowing problems. Other figures put the prevalence at up to 60 per cent, “which may rise to 100 per cent if minor deficits such as minor tongue weakness are accepted as evidence of dysphagia”, according to a 2016 paper in the journal Current Physical Medicine and Rehabilitation Reports (‘Dysphagia Management and Stroke Units,’ Dr David G Smithard).
“In many cases, dysphagia resolves fairly quickly, but in others, the swallow will vary in function,” states the same paper. “Management, at present, is based around texture modification of food/liquids and swallowing manoeuvres. Rehabilitation of swallowing remains in its infancy, but there is a lot of promising research with neurostimulation, medication and devices to strengthen muscles involved in swallowing.”
The HSE’s National Clinical Programme for Stroke has produced a National Guideline for Swallow Screening in Stroke (2017), which aims to support all acute stroke services in the development of a swallow screening service for stroke patients within their organisation.
Worryingly, where dysphagia is not identified and managed, it can severely impact on a patient’s health, with consequences ranging from unintended medication non-adherence, to choking, aspiration pneumonia and even death.
However, many healthcare professionals are unaware when patients may be having difficulties with swallowing their medicines. Furthermore, patients living in the community may not report dysphagia to their GP or pharmacist.
The Society of Hospital Pharmacists of Australia has stated that, where possible, dose alteration should be avoided and alternate dose forms or routes of administration should be found. Likewise, the National Institute for Health and Care Excellence (NICE), UK, recommended for patients with dysphagia that fluids and food should be administered in a form that can be swallowed without aspiration.
Gloup is an OTC swallowing gel for oral medication and it may be able to help patients maintain their treatment regimen. It facilitates the intake of medication in solid form, including tablets and capsules. It works by moistening the mucous membranes in the mouth and throat cavity and allowing the tablets to pass smoothly via the oesophagus to the stomach.
Some preliminary work from The University of Queensland, Australia, has assessed the effect of Gloup on drug dissolution (Crino L, Manrique YJ, Cichero JA, Steadman KJ, eds. Characterisation of Gloup: is it suitable for medication delivery in dysphagic patients? APSA-ASCEPT, 2015).
The authors concluded that Gloup had no effect on drug dissolution, unlike some gum-based thickeners designed to ensure safe fluid delivery in dysphagia.
Symptoms of dysphagia
Being unable to swallow.
Recurrent chest infections.
Patient having the sensation of food getting stuck in their throat or chest or sternum.
Hoarse or wet mouth.
Unexpected weight loss.
Coughing or gagging when swallowing.
Taking longer than usual to finish a meal.
Age-related macular degeneration is the leading cause of sight loss in the over-50s in Ireland, according to the Irish College of Ophthalmologists (ICO).
Without treatment, it is also the commonest cause of legal blindness, affecting over 60,000 Irish people.
AMD awareness week 2018 ‘SightSee with me’ will take place from the 10-14 September. It aims to generate greater public awareness and understanding of AMD and encourage those aged 50 and over to get their eyes tested regularly.
This year marks the beginning of a new decade for the awareness campaign, representing the 11th anniversary of the multi eye-care stakeholder group initiative, supported by the ICO.
Consultant Ophthalmic Surgeon and ICO spokesperson Mr Mark Cahill believed the campaign had been “very effective”. He added, however, that the importance of the symptom of distortion may require better awareness.
Macular degeneration occurs when the macula is unable to function as effectively as it used to.
Dry macular degeneration (non-neovascular), which constituted around 90 per cent of cases, affects the eyes gradually, while wet macular degeneration (neovascular) can develop very quickly and is more serious.
Before the mid-2000s, the treatment possibilities for wet AMD were limited to photodynamic therapy and laser therapy and these were only applicable in a small number of patients. However, wet AMD is now usually treated with intravitreal injections.
According to the ICO, intravitreal injection therapy has proven to be a major advance for patients with wet AMD.
It is known that when wet AMD develops, abnormal blood vessels grow under the macula due to a chemical stimulant called vascular endothelial growth factor (VEGF). Intravitreal injections of anti-VEGF drugs, which block vascular endothelial growth factor, can break the cycle of leakage, bleeding and scar tissue growth. Anti-VEGF treatment offers stabilisation and very often improvement in vision.
Anti-VEGF treatment will be around for “many years to come”, predicted Mr Cahill. He also pointed out that a phase 2 trial had recently finished, which centred on a six-month implant of ranibizumab. Three different concentrations were used and the data showed that “the higher concentration was very effective for up to six months in 80 per cent of people and that is a big step forward”.
He added: “Now, that is only a phase 2 trial so it’s got to go through a third phase and then it has to go through a real world period to see if it will get approval.” It would be a game-changer according to Mr Cahill, who also acknowledges that it would entail a surgical procedure, which is not without risk.
Mr Cahill said there is huge demand for AMD treatment and it may be one of the reasons why the cataract surgery waiting list has not been addressed, as available resources have to be targeted towards patients at risk of rapidly losing their vision. Staff in eye care services have worked incredibly hard to ensure greater volumes of patients are seen, he added.
The ICO advises that “regular eye examination with the eye doctor are recommended especially if there is a family history of the condition. This should be done every two years for the over-55s and annually if there is any hint of AMD. It is important that patients self-monitor using an AmSler grid between visits.
Autism is defined in the ICD-10 as an abnormal or impaired development before the age of three years, in at least one of the following areas: Reciprocal or expression of language as used in social communication; the development of selective social attachments or of reciprocal social interaction; and functional or symbolic play.
To get the diagnosis of autism, you have to have at least two of the following four features: (a) Failure to adequately use eye-to-eye gaze; (b) failure to develop peer relationships; (c) lack of socio-emotional reciprocity; and (d) lack of spontaneous seeking to share enjoyment.
This must be followed by at least one item from the following list: (i) Delay or total lack of development of spoken language; (ii) relative failure to initiate or sustain conversational interchange; (iii) stereotyped and repetitive use of language; and (iv) lack of variate spontaneous make-believe play.
This has to be followed by at least one of the following items: (a) An encompassing preoccupation with one or more stereotyped and restricted patterns of interest; (b) preservation of sameness; (c) stereotyped and repetitive motor mannerisms; and (d) preoccupations with part-objects or non-functional elements of play materials.
Asperger’s syndrome, as per ICD-10, has similar features, except that there is no clinically significant general delay in spoken or receptive language or cognitive development. This has been deleted from the American Psychiatric Association’s DSM-5, and will be deleted from ICD-11, most likely, in its final approved version (draft version now available for debate).
History of diagnosis of autism
There has been a massive broadening and evolution of the concept of autism over the past three-quarters of a century. Hans Asperger described it first in modern times, in 1938. Leo Kanner published a classic account in 1943, having got the features from two of Asperger’s colleagues who had emigrated to America at the time of World War II to work with Kanner. The prevalence of autism depends on whether you use old, narrow, out-of-date concepts of autism or new, broader concepts of the condition.
The original prevalence studies of autism in Ireland were conducted by McCarthy, Fitzgerald and Smith and showed a prevalence of 4 per 10,000 in the old Eastern Health Board in Ireland. The current prevalence from the US Centers for Disease Control and Prevention (CDC) in 2016 put the prevalence of autism at one-in-68. I believe that is the correct prevalence.
Autism is under-diagnosed in Ireland and often comorbidities, (which often co-occur) — like attention deficit hyperactive disorder (ADHD), oppositional defiant disorder, dyspraxia or depression — are often diagnosed first and the fundamental problem of autism is missed, with serious and detrimental consequences for the child.
Early diagnosis is critical for a good outcome and there is universal agreement on the critical importance of this early diagnosis and interventions. One of the problems is that the UK National Institute for Health and Care Excellence (NICE) guidelines are not followed. They are very clear that the diagnosis of autism is a clinical diagnosis by an expert in the area of autism. They do not recommend any current test, questionnaire, or structured interview for the diagnosis of autism. Unfortunately, in Ireland, the Autism Diagnostic Interview-Revised (ADI-R) is often regarded as the gold standard diagnosis. It is far from this. It is a very reasonable instrument to use in research, because researchers can compare their findings on this instrument between countries. Unfortunately, in clinical practice, it is often not suitable because parents come to me saying that their child is ‘ADI-R negative’, which to them and to everyone else means that the child does not have autism. Of course, the parents themselves, the schools and everybody else can see clearly that they have autism, as defined by the broader autism phenotype, which is accepted throughout the world now.
If they do not get a diagnosis, then it is a tragedy for the parents, for the child themselves and for the schools, because the child is deprived of early intervention services, special needs assistants and home tuition if necessary, if they are at a very young age. They are also then deprived of the specialised speech and language therapy and occupational therapy they so urgently need.
It is hardly surprising that this leads to massive frustration for parents, teachers and for the child themselves and these children often become very depressed, very anxious, etc. They also develop behavioural disorders, particularly oppositional defiant disorder. Prof Dorothy Bishop, Professor of Developmental Neuropsychology at the University of Cambridge told Adam Feinstein, who wrote a book called Autism in History, that, “the main problem with the ADI-R is not just the financial cost (though that is certainly prohibitive), but also the cost in time; time for training, time for administration, and time for scoring and consensus coding”. Prof Bishop also stated that “if it could be shown that there were real benefits in accuracy of diagnosis from adopting this lengthy procedure, then I would be happy to say, ‘okay’, but, the originators of this instrument have never demonstrated that you actually need such a long process; it is really more an article of faith with them”.
For me, faith is a religious concept. The real issue is that the concept of autism has greatly expanded, as research into what autism is has been carried out. Old-fashioned narrow concepts, which are still being used, have no place in autism diagnosis today. The International Meeting for Autism Research in London in May 2008, which many of the most experienced researchers in autism in the world attended, “lambasted the tool (ADI-R) for missing many cases of autism” and maintained that it was an expensive and “ineffective instrument”. Prof Bishop stated that even after using this instrument, there was no choice but “to seek expert clinical opinion”.
The British Journal of Psychiatry stated in August 2017 that the ADI-R was significantly “under-diagnosing toddlers”.
Prof Gillian Baird previously showed that if you use narrow criteria for autism, “you get a prevalence of 25 per 10,000 and when you use the broader, current criteria, you get a truer rate of 116 per 10,000”. The tragedy is that you miss over three-quarters of the patients with autism if you use narrow criteria and deprive these children of critical early interventions.
Another tragedy in relation to autism was that Bruno Bettelheim propagated the ‘Refrigerator Mother’ theory, first proposed by Kanner, as a cause of autism. This was a total tragedy for parents with children with autism. Sometimes now children with autism are diagnosed as having attachment disorders and the autism is missed and again, this allows the blaming of the mother to enter by the ‘back door’.
Autism is a neurodevelopmental disorder and indeed, the major portion of psychiatry is now dealing with neurodevelopmental disorders, which also include ADHD, global developmental delay, communication disorders, language disorders, speech-sound disorders, specific learning disorder, developmental co-ordination disorder, stereotypic movement disorder and tic disorder, according to the DSM-5. Indeed, many psychiatrists see schizophrenia and bipolar disorder as also neurodevelopmental in origin.
There is a huge amount of overlap between these disorders. Indeed, these disorders need to be checked for by a child psychiatrist every time they see a patient referred for child psychiatric assessment.
The future of psychiatry will be neurodevelopmental. Unfortunately today, there is massive emphasis on parenting skills, both in child psychiatry and in the wider media. A great deal of this is misguided and is simply blaming the mother from a new position. In my view, over 95 per cent of parents are good enough in their parenting. Heritability of autism is about 90 per cent, although various figures are given around that position. It is nothing to do with poor parenting; it has major neurobiological underpinnings. Neurochemical abnormalities at the synaptic cleft are important, as indeed are connectivity issues in the brain. The pathophysiology involves discussions of the serotonin system, the GABA system, reelin, neurotrophins, neuroligins and neurexins.
Autism is neurobiologically heterogeneous and areas researchers are focusing on include the limbic system, cerebellum, brain stem and prefrontal cortex, as well as the amygdala.
There is no aetiology-based intervention for autism spectrum disorders, but there are many interventions that are extremely valuable, and even more valuable if the child gets an early diagnosis with the possibility of these earlier treatments. I am being referred patients now around one-and-a-half years old, or indeed younger, for diagnosis. Many of these early referrals would be siblings of patients with autism who have an increased risk. There remains no definitive treatment for autism, although many make such claims, but there is no scientific evidence for them. At the same time, there is no doubt that various interventions — including speech and language therapy, occupational therapy, behavioural therapy and high-quality early intervention education — all play a significant role and are very valuable when applied as a group of interventions.
Extraordinary claims were made for applied behavioural analysis and claims of amazing results with this treatment were made in 1987, when Lovaas carried out a study which, according to Dr Catherine Lord, a psychologist who specialises in autism, “produced extraordinary results, both in the scope of improvement of some children”, who are described as, “indistinguishable from normal”. Others found it impossible to replicate these findings in follow-up research. Some of these children were noted to show robotic behaviour, lack of emotion and an inability to use trained skills outside the school where these were applied. At the same time, as part of a multidisciplinary package, applied behaviour therapy does have a role. It is the excessive claims that have been the problem.
Another programme that has been of benefit is Treatment and Education of Autistic and Related Communication Handicapped Children (TEACH). This programme helps workers to understand the autism culture and identifies emerging skills, providing a basis for individual educational programmes. It breaks down complex behaviour into basic components and skills, which are taught in a hierarchical manner with repeated practice. It involves a great deal of visual learning. Carol Gray’s Social Stories, which explain the why and how of trouble social situations, can be of use. These involve short scripts tailored to the needs, interests and abilities of the child.
In addition, programmes like the Hanen Speech and Language Programme for Autism and pragmatic language therapy can also be useful. Other interventions that make clinical sense, including using the Mind Reading Skills CD-ROM of Simon Baron-Cohen, helping persons on the autism spectrum to read non-verbal behaviour and to understand emotions and to see things from other people’s perspective.
Occupational therapy is valuable for sensory issues, which are extremely common in autism and indeed are part of the diagnostic process now in DSM-5. These sensory problems often cause huge behavioural problems in school and outside school, when children with autism become overwhelmed by sensory inputs.
References on request
Valsartan is an angiotensin receptor blocker (ARB) that prevents angiotensin II from binding to angiotensin II receptors, and thereby reduces blood pressure (BP). Valsartan can be used as monotherapy, but most often it is combined with a diuretic and/or calcium channel-blocking drug in a single-pill combination (SPC) for the treatment of hypertension and heart failure. Some 13 valsartan drugs are listed in MIMS, many of which are SPCs allowing for increasing doses of the ingredient drugs within the SPC combinations. Estimates vary, but perhaps between 50,000 and 60,000 patients in Ireland will have had a valsartan-containing drug prescribed.
Within the last few weeks, the Health Products Regulatory Authority (HPRA) has issued a precautionary recall of 15 drugs containing the active ingredient valsartan. These drugs are provided by Clonmel Healthcare Ltd, Rowex Ltd and the Actavis Group PTC. The reasons for this highly unusual action can be studied on the HPRA website and in ‘Dear Doctor’ letters issued by the HPRA. I have listed the salient points from this letter, followed by my response and queries:
These drugs are being recalled as a precautionary measure because the Chinese manufacturer has reported contamination with a probable human carcinogen, N-nitrosodimethylamine (NDMA). This statement from the HPRA raises the question as to whether valsartan drugs from other manufacturers might also be contaminated, or put another way, is this carcinogenic substance a common, or even essential, ingredient from the manufacture of valsartan (and possibly other ARBs)?
The HPRA is actively involved with the European Medicines Agency and with other medicines regulators to determine any possible impact on patients who have been taking these medicines. Presumably the answer to this conundrum will be influenced by the dosage of valsartan prescribed and the duration of exposure to the drug?
It is stated that pharmacists will be able to identify patients on the contaminated drugs and that they should be able to provide an alternative valsartan-containing medicine. This can only be done if valsartan is used as monotherapy, or if there is an exact SPC valsartan equivalent to the one prescribed, because pharmacists in Ireland are not authorised to change prescriptions, and patients taking the contaminated drugs must be referred to their general practitioners if an alternative drug is to be prescribed.
It is possible (perhaps likely) that there will not be sufficient current stock levels of non-contaminated valsartan-containing medicines for doctors and/or pharmacists to provide patients with an alternative valsartan-containing medicine and in this case, patients will also be advised by to attend their doctor. This recommendation, like the one above, may not be immediately feasible because general practitioners, who are often stretched to capacity, may not be able to see patients for some time. In either situation, it would be good clinical practice for general practitioners to assess BP control with 24-hour ambulatory blood pressure measurement (see below).
On 13 July, the US Food and Drug Administration (FDA) recalled valsartan-containing drugs from five companies. The FDA statement reads: “The FDA is currently investigating the levels of NDMA in the recalled products, assessing the possible effect on patients who have been taking them and what measures can be taken to reduce or eliminate the impurity from future batches produced by the company.”
How should patients on valsartan-containing drugs be managed?
The above-listed events are likely to cause much concern for patients taking valsartan drugs for hypertension, and the following recommendations seem reasonable in these difficult and evolving circumstances:
Patients should not stop medication without medical consultation because of the danger of uncontrolled BP predisposing to the cardiovascular complications of hypertension, such as stroke and heart attack.
Pharmacists should be able to determine if the patient is on a contaminated product, and unless a direct alternative is available, patients must be referred to their general practitioner so that an alternative drug can be prescribed. If the valsartan product is not contaminated, there is a possibility that pharmacists will have insufficient valsartan products to satisfy the sudden demand, and it will be necessary to consider changing treatment. It is also possible that patients will ask to be taken off valsartan drugs, even if they are not on the contaminated list, because of anxiety resulting from the valsartan recall.
As to which drug to select as an alternative to valsartan as monotherapy or in an SPC, clearly the choice should be to select another non-valsartan ARB, as presumably the reason for selecting an ARB originally was for the efficacy of this class of drug and freedom from cough, which may occur frequently with an ACE inhibitor.
I have written before on the benefits of using SPCs for the treatment of hypertension,1,2,3 on the basis that the rationale for incorporating a number of drugs within one tablet is based on the following evidence-based facts: Most patients with hypertension require more than one drug to achieve BP control; combination preparations improve BP control; prescribing low-dose drugs in combination causes fewer adverse effects than prescribing maximum doses of any one drug; patient adherence to medication is improved by combination tablets, and finally, the combination approach is cost-effective.
There are excellent SPC combinations of alternative ARBs combined with calcium-channel blocking drugs, and thiazide diuretics in differing strengths, which allow treatment to be increased a number of times while only prescribing one tablet.2
Faced with the inevitable necessity to change medication in many patients with hypertension, we should avail of the opportunity to re-evaluate BP control on the replacement drug by performing 24-hour ABPM. ABPM is recommended by international guidelines as the technique of choice for the diagnosis and management of hypertension.3 ABPM is now reimbursed in general practice and this crisis provides a very positive indication for utilising the technique to achieve 24-hour BP control in patients whose medication with contaminated valsartan drugs must be changed.
Prof Eoin O’Brien is Adjunct Professor of Molecular Pharmacology, The Conway Institute, University College Dublin, Ireland.
1. O’Brien, E. If I Had Resistant Hypertension. Hypertension. 2014;64:e3-6.
2. Dolan E, O’Brien E. Blood pressure variability: Clarity for clinical practice. Hypertension. 2010;56:179-81.
3. O’Brien E, Stergiou GS. Blood Pressure Measurement: A Reappraisal for 21st Century Practice. J Clin Hypertens 2018. In press.
Results of study suggest siblings of patients with rheumatoid arthritis are at increased risk of acute coronary syndrome
The results of a study presented at the Annual European Congress of Rheumatology (EULAR 2018) demonstrate an increased risk of acute coronary syndrome (ACS) in siblings of individuals with rheumatoid arthritis (RA), suggesting shared susceptibility between the two diseases.
Recent studies have demonstrated that severity of RA is associated with the risk of ACS, suggesting that it is the RA disease itself contributing to the excess risk.
A recently-published report demonstrated that despite more efficient control of inflammation in RA during recent years, the excess risk for ACS among patients with RA compared to the general population remains elevated. This suggests there may be a shared susceptibility between the two conditions.
To examine this, study authors investigated the risk of ACS in siblings of individuals with RA. If there were shared susceptibility between the two conditions, non-RA siblings would also have an increased risk of ACS due to their similar genetic set-up and background.
This Swedish Rheumatology Quality (SRQ) register is linked to the Swedish Multigeneration Register, Patient Register, the Cause of Death Register, and the Total Population Register. Through this, investigators identified 7,492 patients with RA from the SRQ (1996-2015) who had 10,671 full siblings; the patients with RA were matched for age and gender with 35,120 comparator subjects, along with their 47,137 full siblings.
Results showed that patients with early RA and their siblings were 44 per cent and 23 per cent more likely to suffer from an ACS event than matched comparator subjects from the general population. A direct comparison of patients with RA to their siblings demonstrated that those with RA had a 19 per cent higher risk of ACS than their siblings.
“Our results provide evidence of shared susceptibility between RA and ACS,” said study author Dr Helga Westerlind, Karolinska Institutet, Sweden. “Although the nature of this needs to be further investigated, we believe that to bring down the cardiovascular risk in patients with RA, cardio-preventive measures must go beyond optimised RA disease control.”
Gout in the elderly linked to higher risk of dementia
The results of a US study presented at EULAR 2018 suggest that gout is associated with a 17-to-20 per cent higher risk of dementia in the elderly.
The study included 1.23 million Medicare beneficiaries, of which 65,325 had incident dementia. In an analysis, which was adjusted for various potential confounding variables, including demographics, comorbidities and commonly-used medications (HR 1.17, 95 per cent CI 1.13-1.21), the results showed that gout is independently associated with a significantly higher risk of dementia. The association was larger in older age groups, females, African-American race and people with higher medical comorbidity.
Subgroup analyses indicated that gout was associated with a significant 20-to-57 per cent (p<0.0001) increase in dementia in patients without key comorbidities: Coronary artery disease (CAD); hyperlipidaemia; cardiovascular disease; diabetes; or hypertension. However, this was not the case in patients with each of these comorbidities, except in patients with CAD.
“Our study found a considerable increased risk of dementia associated with gout in the elderly,” said study author Dr Jasvinder Singh, Professor of Medicine and Epidemiology at the University of Alabama, Birmingham, US. “Further study is needed to explore these relationships and understand the pathogenic pathways involved in this increased risk.”
“We welcome these results, as they contribute to our understanding of the relationship between uric acid and dementia,” said Prof Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. “Previous studies have shown contradictory results, with some indicating an increased risk of dementia, while others reporting the opposite.”
Combining NSAIDs and TNF inhibitors may reduce radiographic progression in ankylosing spondylitis
The results of a cohort study presented at EULAR 2018 showed that, in patients with ankylosing spondylitis (AS) taking TNF inhibitors, the addition of non-steroidal anti-inflammatory drugs (NSAIDs) was associated with significantly less radiographic progression in a dose-related manner at four years.
When looking at specific NSAIDs, celecoxib in combination with TNF inhibitor use was associated with the greatest reduction in radiographic progression, which was significant at both two and four years.
NSAIDs remain first-line therapy for patients with AS. If patients have a poor response, contraindications or intolerance to NSAIDs, they may then be given TNF inhibitors. Current treatment practice is based on symptomatic relief, however there is also some evidence that NSAIDs slow radiographic progression if taken continuously.
The evidence for the impact of TNF inhibitors on radiographic progression is unclear despite their good clinical efficacy. Many patients discontinue NSAIDs when they are put onto TNF inhibitors due to good symptom control; therefore there is very limited data on the impact of combined therapy on radiographic progression.
“Radiographic progression has an important bearing on patient mobility, as well as affecting their general wellbeing and day-to-day living,” said Prof Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. “We welcome these results that support a potential disease-modifying effect in patients with ankylosing spondylitis taking current therapies.”
This prospective cohort study included 519 patients with AS who met the modified New York criteria with at least four years of clinical and radiographic follow-up. The average age of participants was 41.4 years, with an average symptom duration of 16.8 years and three-quarters were male. NSAIDs were used in 66 per cent of patients (half using an index below 50 and half above). TNF inhibitors were used in 46 per cent of patients.
After baseline measures, clinical and medication data were collected every six months and radiographs performed every two years. Radiographic progression was measured using the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Statistical analysis, which accounted for time-varying covariates, was used to estimate the causal effect of TNF inhibitors and NSAIDs on radiographic progression. The analysis was adjusted for gender, race/ethnicity, education, symptom duration, enrolment year, number of years on TNF inhibitors, symptom duration at time of TNF inhibitor start, baseline measurement scores (mSASSS, ASDAS-CRP), current smoking, and missed visit status.
In patients taking TNF inhibitors, the addition of NSAID therapy was associated with less radiographic progression in a dose-related manner at four years. Mean difference in mSASSS between TNF inhibitor use and no TNF inhibitor use at four years was 0.50 (p=0.38), -1.24 (p<0.001), and -3.31 (p<0.001) for no NSAID, low NSAID, and high NSAID use. The mean difference in mSASSS between TNF inhibitor and no TNF inhibitor use for celecoxib was -3.98 (p<0.001) and -4.69 (p<0.001) at two and four years, respectively.
“Our results suggest that the use of TNF inhibitors and NSAIDs, particularly celecoxib, have a synergistic effect to slow radiographic progression in AS patients, particularly at higher doses,” said study author Prof Lianne Gensler, Associate Professor of Medicine, University of California, San Francisco, US.
“This is the first study to compare whether effects are comparable among different NSAIDs in this setting.”
Positive clinical advances in systemic lupus erythematosus
The results of two studies presented at EULAR 2018 demonstrate exciting advances for individuals suffering from systemic lupus erythematosus (SLE).
The first is a phase 2 clinical study of a promising oral treatment, baricitinib. The second demonstrates the effective use of the shingles vaccine in SLE patients who are particularly prone to this infection.
“Novel therapeutic strategies are needed for SLE, which causes significant morbidity and mortality, and so we are delighted to see the positive results from the phase 2 trial of baricitinib,” said Prof Thomas Dörner, Chairperson of the Abstract Selection Committee, EULAR. “In addition, we welcome data on the vaccination of SLE patients against shingles, as currently, there is considerable clinical uncertainty around this issue.”
Treatment of SLE traditionally involves non-specific anti-inflammatory or immunosuppressive medications. However, this approach is ineffective in many patients and can be associated with many undesirable side-effects.
In the new phase 2 study, SLE patients taking baricitinib (an oral selective inhibitor of Janus kinase (JAK)1 and JAK2 approved for the treatment of rheumatoid arthritis in Europe and Japan) had a significant improvement in several clinical outcomes compared to placebo.
This study included 314 patients with SLE receiving stable background therapy who were randomised 1:1:1 to placebo, baricitinib 2mg or 4mg once daily. Patients on baricitinib 4mg achieved significant resolution of arthritis or rash (Systemic Lupus Erythematosus Disease Activity Index 2000, SLEDAI-2K) compared with placebo (67 per cent vs 53 per cent, p<0.05), which was the primary end-point of the study. Patients on baricitinib 4mg also achieved a significantly greater SLE Responder Index (SRI-4) response (64 per cent vs 48 per cent, p<0.05), as well as flare reduction (SELENA-SLEDAI Flare Index), improvement in Lupus Low Disease Activity State (LLDAS) and reduced tender joint count. Rates of adverse events leading to treatment discontinuation and serious adverse events were higher for both baricitinib doses compared to placebo. There were no deaths, malignancies, major adverse cardiovascular events, tuberculosis, or serious herpes zoster infections; one case of deep-vein thrombosis was reported in a patient with risk factors.
“Our results demonstrated significant clinical improvements in SLE patients taking baricitinib versus placebo with an acceptable side-effect profile,” said Prof Daniel Wallace, Professor of Medicine, University of California and Associate Director, Rheumatology Fellowship Programme at Cedars-Sinai Medical Centre in California, US. “We look forward to progressing baricitinib in further clinical studies as a promising new treatment for people suffering with SLE.”
Meanwhile, a separate study showed that the live attenuated shingles vaccine was well tolerated and provoked an expected antibody response in stable SLE patients not receiving intensive immunosuppression.
Patients with SLE are 10 times more likely to contract shingles compared to healthy individuals and it can also affect them at an earlier age.
However, specific guidelines on the use of the shingles vaccine in SLE patients have been lacking, largely due to a theoretical concern of vaccine-induced infection, as well as a lack of clinical or experimental data upon which to base recommendations.
The study presented at EULAR 2018 included 90 patients with stable SLE who were not receiving intensive immunosuppression. All participants had a history of herpes zoster/chickenpox and were randomised to receive shingles vaccine or placebo. After six weeks, antibody levels in the vaccine group increased by 59.8 per cent versus a reduction of 2.1 per cent in the control group (p=0.01) demonstrating the effect of the vaccine. No serious adverse events were reported and none of the patients had clinical shingles infection post-vaccination.
“This is the first randomised, controlled trial to study the shingles vaccine in individuals with SLE. We hope our results will inform guidelines and ultimately lead to the safe administration of the vaccine in appropriate SLE patients to reduce the burden of shingles in these individuals,” said study author Dr CC Mok, Department of Medicine, Tuen Mun Hospital, Hong Kong.
Early, intensive treatment of RA provides long-term benefits and may normalise mortality rates — long-term follow-up study
The results of a 23-year, follow-up study presented at the European League Against Rheumatism (EULAR) Annual Congress 2018 suggest early, intensive treatment of rheumatoid arthritis (RA) has long-term benefits including the normalisation of mortality to levels consistent with the general population.
“We know that the adverse effects of rheumatoid arthritis on the body only become truly apparent after more than a decade,” said Prof Robert Landewé, Chairperson of the Scientific Programme Committee, EULAR. “Therefore, it is really interesting to see these data supporting early therapy after such a long period of follow-up.”
Mortality in patients with RA is higher than in the general population. There have been many advances in management which have demonstrated improved morbidity rates, however, evidence of improved mortality rates has remained elusive.
“Our results confirm that early, intensive treatment of rheumatoid arthritis, including use of glucocorticoids, has long-term benefits,” said Prof Maarten Boers, VU University Medical Centre, Amsterdam, The Netherlands (study author).
“Importantly, this study is one of the first to show a normalisation of RA mortality compared to the general population after 23 years of follow-up.”
This prospective study looked at the rate of mortality after 23 years follow-up of the COBRA (COmbinatietherapie Bij Reumatoide Artritis) trial.
In the original study, patients with early RA were treated with sulphasalazine (SSZ) monotherapy or a combination of SSZ, low-dose methotrexate and initially high, step-down prednisolone.
Results demonstrated the combined therapy regimen offered additional disease control over SSZ alone.
In 2010, after 11 years of follow up, another study showed numerically (but not significantly) lower mortality in patients on the combined therapy regimen compared to patients with SSZ monotherapy.
NSAIDs shown to have causal role in cardiovascular risk of patients with osteoarthritis
The results of a study presented at EULAR 2018 suggest that over two-thirds of the increased cardiovascular risk associated with osteoarthritis is linked to the use of non-steroidal anti-inflammatory drugs (NSAIDs), a mainstay of treatment for this condition.
Recent research suggests that osteoarthritis is an independent risk factor for cardiovascular disease (CVD) and several mechanisms have been suggested to account for this association. One of these is the frequent use of NSAIDs in the treatment of osteoarthritis as they have been shown to be a proven risk factor for CVD.
“The examination of cardiovascular risk among individuals with osteoarthritis is an important area of research as very little is known about the association, despite osteoarthritis being the most common rheumatic disease with high prevalence among the elderly,” said Prof Thomas Dörner, Chairperson of the Abstract Selection Committee, EULAR.
“This study is important because it provides new information about the potential causal role of NSAIDs for the observed cardiovascular complications among individuals with osteoarthritis.”
Results of the study demonstrate that people with osteoarthritis had a 23 per cent higher risk of developing CVD. The increased risk of congestive heart failure (CHF), ischaemic heart disease (IHD), and stroke was 42 per cent, 17 per cent and 14 per cent respectively. Investigators then calculated the impact of NSAID use on the increased risk and found that 68 per cent of the total effect of osteoarthritis on CVD risk was due to NSAID use. The proportion of the increased risk due to NSAIDs seen in CHF was calculated at 45 per cent and more than 90 per cent for IHD and stroke respectively.
This population-based cohort study used data from 7,743 osteoarthritis patients and 23,229 non-osteoarthritis controls matched for age and gender from health administrative data from British Columbia, Canada. Statistical analysis was used which adjusted the results for age, gender, socioeconomic status, body mass index, and several conditions known to be associated with CVD, such as chronic obstructive pulmonary disease (COPD), high blood pressure, diabetes, high cholesterol, and Romano comorbidity score.
“To the best of our knowledge, this is the first longitudinal study to evaluate the mediating role of NSAID use in the relationship between osteoarthritis and CVD in a large population-based sample,” said study author Prof Aslam Anis, School of Population and Public Health, University of British Columbia.
“Our results indicate that osteoarthritis is an independent risk factor for CVD and suggest a substantial proportion of the increased risk is due to the use of NSAIDs.
“This is highly relevant because NSAIDs are some of the most commonly used drugs to manage pain in patients with osteoarthritis.”
The Irish Skin Foundation (ISF) has published a revised and expanded psoriasis patient support booklet.
With up to 100,000 people in Ireland affected by psoriasis, and up to 20,000 of these living with a severe form, the ISF has updated its ‘What you need to know about psoriasis’ support booklet, which is a useful resource to give to patients with psoriasis.
The new edition provides revised information on understanding, managing and living with psoriasis. Updated sections include, what psoriasis is, the different types of psoriasis, treatments available, associated conditions, self-care tips and more.
This booklet, which first appeared in 2014, was extensively revised after wide consultation with people with psoriasis who have contacted the ISF Helpline, dermatology nurses and consultant dermatologists.
Although there is no cure for psoriasis, there are a range of effective treatment options available, which can be offered on a stepladder approach, including dithranol, tar, and UVB phototherapy. For those with moderate- to-severe psoriasis who have not responded to milder treatments, systemic treatment may be needed (eg, ciclosporin, methotrexate, acitretin and fumaric acid esters).
A number of biologic agents have been licenced for the treatment of psoriasis, including TNF inhibitors (eg, adalimumab, etanercept and infliximab), the interleukin (IL) 12/23 compound ustekinumab, and the IL-17A antagonist, secukinumab. These agents have significantly broadened the range and efficacy of treatment options available and revolutionised the care of more severe psoriasis patients.
Key symptoms in psoriasis include:
Red, scaly plaques or lesions with sharply defined edges, that occur most commonly on both elbows, both knees, the scalp, under arms, under breasts, natal cleft and genitalia, or at the site of an injury.
If the scales are gently scraped off, a number of small, bleeding points can be seen underneath.
Nail changes – loosened, thickened or pitted nails.
Plaque psoriasis is the most common form of psoriasis, affecting approximately 90 per cent of patients. The plaques can vary in number, size, and location but the sites most frequently affected, are the knees, elbows, scalp and sacrum. The plaques are often itchy and painful, and can crack and bleed.
Guttate psoriasis usually has a sudden onset with the widespread appearance of small, red teardrop shaped patches less than 1.5cm in size. The onset is often preceded by a streptococcal throat infection. In many cases, the condition disappears by itself after a few weeks or months.
Flexural psoriasis occurs in skin flexures such as under the breasts, in the armpits or the groin. The plaques are usually red, smooth and shiny. There is very little or no scale, due to the presence of sweat. Painful superficial skin fissures sometimes occur in skin creases. Candida albicans can also develops, due to the naturally warm moist environment found in these areas.
Scalp psoriasis affects up to 80 per cent of people with psoriasis and sometimes is the only area of involvement.
A new step-by-step section on treatments for scalp psoriasis has been included in the ISF booklet. This new section includes some useful techniques patients can use at home to treat their scalp psoriasis with over-the-counter and prescribed treatments.
There are a number of other conditions that have been associated with psoriasis including psoriatic arthritis (PsA), which is covered in the booklet.
Studies indicate a wide prevalence rate of PsA among people with psoriasis; anything between 6 and 42 per cent.
Key symptoms associated with psoriatic arthritis include joint pain, especially with redness, swelling, and tenderness; pain in the heel(s) or tennis elbow; finger or toe that is completely swollen (sausage shaped) and painful for no apparent reason; and morning stiffness/pain in the back that improves with movement.
The ISF’s ‘What you need to know about Psoriasis’ support booklet is available free of charge by post or can be downloaded from the ISF website at www.irishskin.ie.
The ISF also operates a free helpline (01 486 6280) and web questionnaire service, providing direct, accessible and specialist guidance and support to skin condition patients.
The ISF also holds regular information and awareness events on various skin conditions, including psoriasis.
Meanwhile, the ISF has pointed out that patients may not be aware that they can claim back money from Revenue for over the counter items used to treat their psoriasis like creams, medications or other aids and appliances in certain circumstances.
Revenue allows for tax back on health expenses incurred in the provision of healthcare, which is defined as the prevention, diagnosis, alleviation or treatment of an ailment, infirmity, defect or disability.
In addition, it also covers cosmetic surgery only as a result of a physical deformity arising from, or directly related to, a congenital abnormity, personal injury or disfiguring disease.
Medicines and associated items that qualify for tax back must be:
(a) Supplied by a pharmacist and
(b) Be written on the medical practitioner’s medical / prescription pad.
Thus, any relevant over-the-counter items prescribed by a medical practitioner can be claimed back under the tax system, at 20 per cent of the cost of the item, once the relevant prescription and pharmacy receipts are kept.
Breast cancer is the commonest, potentially fatal cancer diagnosed in women in Ireland, according to the latest National Cancer Registry Ireland (NCRI) statistics. The median age at diagnosis is 60 – 64 years. Women under the age of 40 have an incidence of 11.93 diagnoses per 100,000 women per year. This patient population poses specific challenges and here we attempt to address some of these, namely pregnancy-associated breast cancer, optimum adjuvant endocrine treatment, fertility post-treatment and inherited breast cancer syndromes.
Pregnancy-associated breast cancer
Pregnancy-associated breast cancer is defined as breast cancer diagnosed during pregnancy or in the first postpartum year. With most pregnancies occurring in women under the age of 40 years, it is this age group that is at risk of pregnancy-associated breast cancer. The incidence of breast cancer increases with age and as increasing numbers of women delay pregnancy, it is possible that pregnancy-associated breast cancer will increase. Several studies have indicated a worse prognosis in those with pregnancy-associated breast cancer; these cancers tend to have higher T and N stages. Even allowing for this, some studies have demonstrated worse cancer-related outcomes for those with pregnancy-associated breast cancer.
No statistics are available at present for the incidence in Ireland, but it is estimated that approximately one-in-3,000 pregnant women will be diagnosed with breast cancer, making it the second most common malignancy in pregnancy. Several challenges arise in this setting, including difficulties in diagnosis, optimum timing of surgery, scheduling of systemic treatment and maximising neonatal outcomes. The Royal College of Obstetrics and Gynaecology recommends that all women presenting with a breast mass during pregnancy be referred for evaluation to a specialist breast unit. Surgery is safe during all stages of pregnancy, but should be delayed until after the first trimester, when the risk of miscarriage diminishes. Radiation is not recommended for patients who are pregnant. Cytotoxic chemotherapy use is generally initiated in the second trimester, with evidence for good neonatal outcomes with the use of anthracycline/cyclophosphamide combinations. Due to the risk of oligohydramnios, trastuzumab is not given during pregnancy. In general, cytotoxic chemotherapy is held at 35 weeks to reduce the risk of neonatal neutropaenia. Endocrine therapy is not given until after delivery.
Optimum adjuvant endocrine treatment
Tamoxifen is a selective oestrogen receptor modulator and has been a mainstay of treatment for women with oestrogen receptor-positive breast cancer for decades. Its use has been refined over this time, with it now being used primarily in pre-menopausal women. However, even with five years of adjuvant tamoxifen therapy, some patients will relapse and so strategies to optimise adjuvant endocrine treatment in patients have been further explored. Such strategies include prolonging the duration of therapy or more aggressive suppression of hormonal function.
Two large multicentre randomised studies evaluated the utility of extended tamoxifen therapy, beyond the standard five years, ATLAS and ATTOM. Initial results of both studies suggested that there was no survival benefit to this therapy. Follow-up survival data, however, demonstrated a benefit to extended adjuvant tamoxifen, which appeared after the 10-year period of treatment and, therefore, this is a potential therapeutic strategy for these patients. Such a prolonged course of therapy might be best targeted at patients with a persistent elevated risk of relapse after five years of therapy, eg, those patients with pathologically involved lymph nodes at diagnosis.
Two other large studies have evaluated the optimum intensity of adjuvant endocrine treatment. The TEXT and SOFT studies sought to establish if further oestrogen suppression with triptorelin, a GnRH agonist, in combination with either exemestane (an aromatase inhibitor) or tamoxifen would improve survival. The TEXT study evaluated exemestane, a steroidal aromatase inhibitor, in combination with triptorelin, a GnRH agonist compared to tamoxifen and triptorelin. This trial demonstrated an improvement in disease-free survival in those patients on exemestane and triptorelin compared to tamoxifen and triptorelin. No overall survival benefit was seen. In the SOFT study, when compared to tamoxifen alone, tamoxifen and triptorelin demonstrated a 4 per cent disease-free survival benefit, with a 7 per cent disease-free survival benefit in those on exemestane and triptorelin. Unlike the TEXT study, an overall survival benefit was seen, largely coming from the higher risk group (those patients requiring adjuvant chemotherapy). There is, however, a higher adverse effect rate, with increased vasomotor symptoms, decreased libido, vaginal dryness, and musculoskeletal symptoms among others. Given the modest benefit, this combination approach is usually offered to those patients at higher risk of recurrence (especially very young patients, ie, those under 35 years of age).
In younger breast cancer patients, preservation of fertility is often a key priority. There are several concerns at this time – preventing premature ovarian failure, timing of future pregnancies to maximise oncologic and fertility outcomes and the need to avoid teratogenicity with ongoing treatment.
Fertility preservation prior to embarking upon treatment can be considered in those patients who wish to do so. There are two main techniques that are available to patients: Oocyte or embryo preservation. Oocyte preservation requires a short cycle of stimulatory hormonal therapy, after which the oocytes are retrieved and rapidly frozen. In Ireland, embryo preservation is offered to those with a long-term partner. The first step is as for oocyte preservation, with subsequent fertilisation and embryos are then frozen. With modern oocyte stimulation techniques, delays to the initiation of chemotherapy can be kept to a minimum.
Administration of GnRH analogues during chemotherapy may help preserve ovarian function. A recent meta-analysis of the use of GnRH analogues, pooling the data from several international studies, demonstrated improved post-chemotherapy fertility. The authors classified this as (1) improved premature ovarian insufficiency rate (variously identified as failure to return to normal menstruation within six-24 months depending on the study), (2) higher pregnancy rate, and (3) reduced rates of amenorrhoea at two years. They did not find any evidence of excess cancer-related mortality in those who received the GnRH analogue. Thus, this provides a potential option for these patients.
Pregnancy post-breast cancer diagnosis poses challenges in treatment continuity and risks of recurrence. Data is sparse, but a recently reported retrospective study examining 1,200 patients did not demonstrate any increased risk of recurrence in those women who became pregnant post-early breast cancer diagnosis.
Timing of pregnancy can be a challenge. The risk of recurrent cancer in patients with triple negative and HER2-positive breast cancer is highest in the first two years after diagnosis and the advice for these women is generally to avoid pregnancy until this period has passed. The situation is more complex for those with oestrogen receptor-positive breast cancer. For these patients, adjuvant endocrine therapy is an essential part of treatment, with the goal of treatment being oestrogen suppression. However, tamoxifen is contraindicated in those planning a pregnancy due to the risk of teratogenicity. It is therefore recommended that such women stop tamoxifen for three months prior to attempting to conceive. The reduced duration of therapy may expose the patient to a higher risk of relapse and patients must be counselled on this risk.
Another factor to consider in the young woman post breast cancer diagnosis is the potential teratogenicity of therapies. As outlined in this article, cytotoxic treatments are carefully scheduled. Once commenced on adjuvant endocrine therapy, patients should be advised to use effective contraception. Available data on tamoxifen suggests there is a risk of congenital malformations and a three-month washout period is advised.
Inherited breast cancer syndromes
When a young woman is diagnosed with breast cancer, the question of an underlying genetic predisposition often arises. Most cases of breast cancer are not caused by an identifiable inherited predisposition, instead having a multifactorial origin. However, 5-10 per cent of breast cancers can be attributed to a single gene mutation, which significantly increased the predisposition to cancer development. Between 80-90 per cent of all hereditary breast cancers are associated with mutations within the BRCA1 and BRCA2 genes, with less common syndromes including Li Fraumeni syndrome, Peutz-Jeghers syndrome, Cowden syndrome and ataxia/telangiectasia also causing an increased risk. To identify those at risk, a complete, three-generation family history must be obtained from patients. A complete discussion of the intricacies of each syndrome is beyond the scope of this article and we will focus on BRCA syndromes. Various testing platforms exist, ranging from those examining specific targets (such as in a family with a known BRCA mutation) and those offering panel testing, assessing risk associated with more than one syndrome.
BRCA1 and BRCA2 function as tumour-suppressor genes, playing a role in DNA repair and are inherited in an autosomal dominant fashion with incomplete penetrance. Testing for BRCA1/2 mutations should be performed in the context of pre- and post-treatment counselling. The Manchester Criteria are used to help determine which patients should be offered testing. Those patients who are found to be carriers can then discuss appropriate surveillance and potential risk-reducing procedures. More widespread population-based screening is considered in some centres. In this instance, BRCA1/2 testing is offered to all patients under 40 years, or all those with triple-negative breast cancer.
Managing breast cancer in young women is a complex challenge, requiring balancing of multiple factors. When breast cancer complicates pregnancy, co-ordination between the oncologist and obstetrician is imperative to optimise outcomes. Close communication between all members of the multidisciplinary team helps to facilitate fertility preservation and genetic testing. The most recent data available offers several combination strategies to optimise adjuvant endocrine therapy for these patients.
References on request