All of the study participants belonged to one of three groups defined by the presence of separate communities containing six to 12 genera of bacteria, according to Claire Fraser, PhD, of the University of Maryland School of Medicine in Baltimore, and colleagues. Each genus can contain several individual bacterial species.

Although none of the three bacterial communities were associated with body mass index or any of the metabolic syndrome components, 26 of the individual bacterial species were associated either positively or negatively with BMI, serum triglycerides, HDL cholesterol, total cholesterol, fasting glucose levels, and C-reactive protein, the researchers reported online in PLoS One.

That suggests “that certain members of the gut microbiota may play a role in these metabolic derangements,” they wrote, adding that the cross-sectional nature of the data precludes an assessment of the causality of the relationships.

“Follow-up longitudinal studies can begin to address whether specific gut bacterial taxa play a causal role in the predisposition to or development of the metabolic syndrome, as well as the utility of interventions that modulate the composition of the gut microbiota to mitigate the risk of cardiovascular complications associated with metabolic syndrome,” they wrote.

Obesity is believed to be caused by both environmental and genetic factors, and some studies have linked obesity to gut bacteria, with a range of proposed mechanisms. However, results from the various studies have been conflicting depending on the population studied.

Fraser and colleagues explored the issue among men and women belonging to the Old Order Amish sect in Lancaster County, Pa. Within the community, there is a high degree of uniformity of genetic background, socioeconomic status, and lifestyle, which reduces potential confounders.

The researchers collected stool samples from 310 adults ages 20 to 80 (64% female). Women had a higher average age and BMI and were more likely to have at least one component of the metabolic syndrome (38.9% versus 26.8%), which was defined by elevated BMI, blood pressure, fasting triglycerides, and fasting glucose, and low fasting HDL cholesterol.

Among the 203 genera of bacteria identified, there were three communities of interacting bacteria. The participants were assigned to one of three groups depending on which community was most prevalent in the gut — 47% had a community dominated by Prevotella, 39% had a community dominated by various genera from the phylum Firmicutes, most commonly Oscillospira, and 14% had a community dominated by Bacteroides.

After adjustment for age and sex, none of the bacterial communities were associated with BMI or the components of the metabolic syndrome, but 26 bacterial species from the phyla Bacteroidetes, Firmicutes, and Actinobacteria and the order Clostridiales were related to various metabolic syndrome traits.

While the already-approved Aricept and Namenda medications have shown promise for temporarily easing symptoms, what’s desperately needed are treatments that will reverse or prevent the brain decline produced by Alzheimer’s.

Researchers are seeing promising results of the first long-term clinical trial that measured stabilization of Alzheimer’s symptoms, including thinking, memory, daily functioning and mood. The early stage results were presented at the Alzheimer’s Association International Conference in Vancouver, British Columbia, this week.

The treatment, Gammagard by Baxter, is an intravenous immune therapy that is already approved for treating other immune disorders and infections.

The small study of Gammagard included 16 subjects with mild to moderate Alzheimer’s disease who were in the first part of the trial and agreed to continue the study for three years.   What’s exciting about the results of this trial is that doctors say  four of the patients who continued treatment at the highest dosage showed a stop in the worsening of symptoms, making this small study the first to report symptom stabilization without decline over that longer time span.  Larger studies will begin later this year.

In addition to the Gammagard findings, researchers reported updates on three new pre-symptomatic Alzheimer’s disease studies that are scheduled to begin in the near future. Because recent clinical trials have produced disappointing results, there’s a belief among many Alzheimer’s researchers that the key to cracking the code for treatment success is by testing therapies on people who are predisposed to Alzheimer’s disease, yet are not symptomatic.

Several trials in the future will focus on that, including trials in a rare population living near Medellin Colombia that is prone to genetically-caused, early onset Alzheimers.

“Improving detection technologies and updated diagnostic guidelines are enabling the detection of early changes in the brain and subtle cognitive deficits that are consistent with what is known as pre-symptomatic Alzheimer’s,” according to William Thies, the Alzheimer’s Association chief medical and scientific officer.

Thies says people in this group are the ideal subjects for prevention trials, which might delay or slow the progression of their disease.

Approximately 5.4 million Americans live with Alzheimer’s disease and it’s the 6th leading cause of death in the U.S. Alzheimer’s is the most common type of dementia, a term used to describe memory and intellectual loss severe enough to interfere with daily activities. It’s caused when deposits of proteins form in the brain and preventing it from properly functioning.

Researchers from Monash University in Australia and Lancaster University in the UK, write about their work in the 2 August online issue of Current Biology.

The answer to the biological puzzle of why women live longer than men may lie in the tiny “power packs” of the body’s cells which harbour mutations that are more harmful to males than to females, scientists have discovered.

Hope for more effective TB treatment

Hopes of a new, more effective therapy for tuberculosis have been raised following the results of early trials.

The study showed three drugs given in combination killed more than 99% of TB bacteria after two weeks of treatment.

The therapy appeared to be equally effective on the drug-resistant form of the disease in the trials of 85 patients, a team led by Stellenbosch University in South Africa reported.

Larger studies are now taking place to further test the technique.

TB is one of the oldest and most deadly infectious diseases.

About 1.4m people a year die each year from it, mainly in developing countries.

Current treatments usually involve people taking drugs daily for six months.

The drug-resistant strain is much harder to treat and can involve up to two years of therapy.

Of the three drugs used in this study, published in the Lancet, one is new, while another is not yet licensed.

Andreas Diacon, lead researcher for the trial, said: “The results of this study give healthcare providers on the front-lines of the TB epidemic hope for better, faster tools needed to stop this disease.”

Dr Mario Raviglione of the World Health Organization said the new treatment signifies ”major progress”

Mario Raviglione, a TB expert at the World Health Organization, said: “The results look strongly promising from this early trial.

“We could shorten drug regimens substantially for everyone, regardless of whether the form of TB is sensitive or multi-drug resistant.”

There are three general types. Atopic eczema is ‘endogenous’ eczema which is triggered by allergy, and may be associated with discoid and pompholyx eczema. Exogenous eczema is triggered by irritants, allergy and sunlight. Unclassified eczema covers a miscellany of other itchy scaly conditions including gravitational eczema.

Although this makes the topic sound complicated, there are general principles for management which make it simpler for the clinician. The most important is that eczemas are usually chronic conditions and so the key to treatment is a clear explanation of the condition to patients. Patients need long-term support with their condition from their GP.

Although acute presentations are uncommon, many patients need frequent reassessment of the best treatment of their condition, and ongoing encouragement to persist with all treatments.

Atopic eczema

Atopic eczema is common in childhood and starts between four months and two years. Adult onset is also possible but much less common. Most children who have atopic eczema grow out of it, with only about 1-2 per cent of adults affected. Children who develop atopic eczema are more likely to develop asthma and hay fever.

The rash often starts on the face and scalp and develops later on flexures on the knees and elbows. Children have a tendency to scratch and so the rash becomes excoriated. Bacterial infection is a common complication as the defence mechanisms of the skin are compromised.

To treat atopic eczema, in addition to using general measures (see box), antibiotics may be needed for secondary infection and antihistamines to treat itching. Antihistamines are useful in the night-time to prevent scratching during sleep and to aid sleep. The most effective anti-histamines are the ones more likely to cause drowsiness.

Less common treatments are phototherapy, oral cortico-steroids, topical calcineurin inhibitors such as pimecrolimus cream or tacrolimus ointment, ciclosporin and azathioprine.

Aggravating factors are cold weather (which causes dry skin), inconsistent use of treatments and bacterial and herpes simplex infection (which will need to be treated).

Discoid eczema

Discoid eczema can affect any part of the body, particularly the lower leg. It appears as round or oval pink or brown patches sometimes singly, but often in multiples. Patches are usually itchy. When they settle after weeks or months patients may be left with altered skin colours, sometimes darker and sometimes lighter – postinflammatory hyperpigmentation or hypopigmentation.

Pompholyx eczema

Pompholyx eczema affects the hands and feet. Initially there are tiny blisters deep in the skin of the palms, fingers, instep or toes, which are very itchy.

In the mild form the symptoms are minimal but some patients develop blisters and deep painful skin cracks which prevent work. The condition tends to be chronic and as one area heals another starts the cycle of blistering and then cracking. Pompholyx around the nail folds may cause nail dystrophy.

Staphylococcal infection is common. Many also patients have nickel allergy. Some patients are prone to develop it after stress or anxiety.

Treatment follows general principles. Infection and allergy should be considered. A few patients may also benefit from PUVA, methotrexate, dapsone, azathioprine and botulinum toxin (to prevent sweating).

Irritant contact dermatitis

Irritant contact dermatitis is caused by chemicals or physical agents damaging the skin.

Common causes are water, detergents, solvents, adhesives and friction. In infancy napkin dermatitis occurs where there is prolonged contact between skin and urine. Often more than one cause is present.

The skin is initially damaged superficially so that the irritants penetrate more deeply and cause further damage by triggering inflammation.

The initial area of inflammation is where the irritant has been in contact with the skin. Sometimes there is spread to other skin areas, but if this occurs it is more likely that there is allergic contact dermatitis.

Where the cause of the eczema is not obvious patch testing will help in diagnosis. Infection is common and flucloxacillin (or erythromycin) may be needed.

Allergic contact dermatitis

Allergic contact dermatitis may be difficult to distinguish from irritant contact dermatitis, because the rash comes up hours after contact with the substance causing it.

It can spread to areas of skin not in contact with the allergen. It often settles over a few days unless contact reoccurs. It also differs from urticaria, which has an immediate rash with skin contact.

The history of contact is sometimes helpful in diagnosis, for example with nickel allergy occurring after skin contact with nickel in a stud on the waistband of a pair of jeans.

Patch testing is very useful in determining the cause of the skin response so that if it occurs again the agent can be avoided.

Gravitational eczema

Gravitational eczema is an itchy rash found on the legs. It is caused by back pressure on the skin when the veins in the legs do not drain blood back into the body effectively. Other names for it are varicose eczema or stasis eczema.

The most common causes are varicose veins (back pressure due to failure of venous valves from low-pressure to higher-pressure drainage systems) and after a DVT. The rash starts at the bottom of the leg and may be in a patch in front of the inner ankle swelling upwards, or it may be present around the whole shin.

In addition to the usual treatments, additional measures that may help are elevation of legs while sitting so that the ankles are above the level of the hips, graduated compression stockings, and sometimes surgery to the varicose veins if there is ulceration of the skin.

General principles for treatment

• Reduction of exposure to trigger factors (where possible).
• Regular emollients (moisturisers) and soap substitutes.
• Intermittent topical steroids.

Patient resources

www.patient.co.uk has four useful patient information leaflets:

• Eczema – atopic.
• Eczema – emollients.
• Eczema – fingertip units for topical steroids.
• Eczema – triggers and irritants.

References

• Hayes P, McKay T. Churchill’s Pocketbook of Medicine. Churchill Livingstone.
• Website containing full list of likely skin allergens:www.dermnetnz.org/dermatitis/contact-allergy.html.

Anxiety is a normal physiological and psychological reaction to stress or imminent danger. Anxiety can be beneficial as it enables us to stay focused and motivated to deal with the stressors that cause it.

In 1908, Yerkes and Dodson suggested that anxiety can be healthy and boosts performance. However, as the anxiety or arousal levels continue to increase beyond the realms of one’s endurance, performance invariably diminishes.

Anxiety becomes pathological when it presents frequently in the absence of a real threat and is disproportionately severe in intensity to a degree that it impairs a person’s life.

Anxiety disorders can be broadly classified into phobic anxiety disorder (social phobia, agoraphobia and specific phobias) and other anxiety disorders, including panic disorder and generalised anxiety disorder (GAD).

Anxiety disorders are one of the most common psychiatric disorders. The worldwide lifetime prevalence of all anxiety disorders is 16.6 per cent.¹The 12-month prevalence of GAD, agoraphobia (plus panic disorder), social phobia and specific phobia is 1.5 per cent, 2 per cent, 2 per cent and 7.6 per cent, respectively.²

Females are twice as likely to have an anxiety disorder as males, with the exception of social phobia, where the ratio is 1:1.

Genetic contribution
All anxiety disorders, and panic disorder in particular, are more common in first degree relatives of affected patients. This is supported by a higher concordance for GAD in twin studies.

However, the genetic contribution to the aetiology of anxiety disorders is poorly understood due to the complexity of interaction between environmental and genetic factors, as well as the lack of adoption studies.

Neurotransmitters and hormones
The three main putative neurotransmitters associated with anxiety disorders are gamma-amino-butyric acid, serotonin and noradrenaline.

The efficacy of benzodiazepines, SSRIs and tricyclic antidepressants in managing anxiety symptoms is regarded as confirmatory evidence of the involvement of these neurotransmitters in the pathophysiology of anxiety disorders.

Stress also causes increased release of corticotropin-releasing hormone, which in turn increases the level of cortisol. Increased cortisol level causes heightened arousal and when chronically secreted also has a contributory role in medical conditions, including hypertension and osteoporosis.

Patients with panic disorder may have heightened autonomic arousal even in the absence of threatening situations.

Life events
Adverse life events and early life experiences also have aetiological significance in the development of anxiety disorders.

Another proposed theory is the manifestation of anxiety symptoms through classical conditioning in response to environmental stimuli.

Psychoanalytical theories propose that anxiety is a result of a weakened ego that is in conflict with the Id, super-ego or the outside world.

Section 2: Making the diagnosis

The primary pathophysiology in all anxiety disorders is autonomic overactivity along with psychological arousal. Peripheral symptoms include palpitations, tachycardia, dizziness, shortness of breath and hyperventilation, sweating, tremors, restlessness and GI upset.

A range of other symptoms secondary to autonomic arousal may be present, such as urinary frequency and headaches.

The psychological arousal can present as impaired concentration, distorted perception of time and space, irritability and selective attention on environmental cues that exacerbate anxiety symptoms.

Many symptoms of anxiety are similar in all disorders, however other clinical features are exclusive to particular types of anxiety disorders (see box).

Comorbidity
Anxiety disorders seldom present as an isolated diagnosis.⁴ The most common comorbidity is another anxiety disorder.

In a 32-year prospective cohort study, 72 per cent of lifetime anxiety patients had a history of depression and 48 per cent had a history of anxiety disorders.⁵

Patients with comorbid anxiety and mood disorder are more disabled than patients with pure anxiety or mood disorder.⁶

Differential diagnosis
Differential diagnosis includes other anxiety disorders, mood disorders, personality disorder, including anxious-avoidant personality disorder, and illicit substance misuse.

Patients with schizophrenia may present in a prodromal phase with vague anxiety symptoms before the onset of full-blown illness.

Anxiety symptoms in schizophrenia can be vague, ill-defined and bizarre. The insight into the irrationality of anxiety symptoms that is so well preserved in anxiety disorders is also lacking in schizophrenia.

Panic attacks can be the only presenting complaint in a range of medical disorders, including endocrine disorders, such as thyroid dysfunction (both hypoand hyper-), hyperparathyroidism, episodic hypoglycaemia, cardiovascular causes including MI and angina, and neurological disorders.

This list is not exhaustive and appropriate investigations should be performed if there is suspicion of an underlying medical disorder.

Investigations
Psychiatric symptoms are often non-specific and can belie an underlying medical disorder.

Careful attention should be paid to other associated symptoms, pre-existing risk factors and atypical presentations.

The initial investigations should include FBC, LFT, U&Es, TFT, blood glucose and urine drug screen. Cardiac and CNS causes should be ruled out with appropriate investigations.

Section 3: Managing the condition

NICE guidelines recommend psychological treatment as the first-line treatment.

A Cochrane review of psychological treatments concluded that cognitive behavioural therapy (CBT) has strong evidence supporting its efficacy in alleviating symptoms of GAD.⁷

A total of 46 per cent of patients post-CBT showed clinical response, compared with 14 per cent of patients on waiting lists. CBT was shown to improve both anxiety and depressive symptoms.

Conclusive evidence for long-term efficacy of CBT in GAD is lacking. There is evidence to support the use of CBT in social phobia and other specific phobias, including agoraphobia.

Exposure treatments, such as systematic desensitisation, are effective treatments for resolving avoidance behaviours which are critical in the maintenance of phobic illnesses.

Exposure treatments do not have a role in the treatment of GAD as triggers in GAD are nonspecific. On their own, relaxation treatments are generally ineffective.

Benzodiazepines
Benzodiazepines are the most rapid and effective treatment of anxiety disorders and can be useful in facilitating commencement of other treatments. However, their long-term efficacy is poor. Benzodiazepines are well known to cause dependence.

There is already a high prevalence of alcohol and drug misuse in patients with anxiety disorder, therefore warranting extra caution when prescribing benzodiazepines.

Antidepressants
SSRIs are the first choice medications for anxiety disorders and have extensive evidence to support their superior effect compared with placebo.

They are generally well tolerated, cause better symptom control of anxiety and comorbid depressive symptoms, and are associated with longer remission periods.

In order to maximise compliance, patients should be advised that there is a two to four-week latency period in the therapeutic effects of SSRIs.

Tricyclic antidepressants are as efficacious as SSRIs, however due to a higher incidence of anticholinergic side-effects they are generally not used as first-line medications.

Other antidepressants that can be considered are selective serotonin and noradrenaline reuptake inhibitors, such as venlafaxine and duloxetine.

Other medications
Buspirone is a 5-HT1a receptor partial agonist anxiolytic drug.

It has a slower onset of action and, unlike benzodiazepines, lacks euphoric effect and has a low potential for dependence.

It is best used as an adjunct with pre-existing treatment for GAD. It is not an effective treatment for panic disorder. Beta-blockers may help with short-term symptomatic relief in performance-related anxiety, such as social phobia.

Monoamine oxidase inhibitors are the most effective treatment for social phobia but they are rarely used due to diet-related restrictions and their pharmacological interactions.

Section 4: Prognosis

There are only a handful of prospective studies which ascertain the natural progression of anxiety disorders.

In a 12-year follow-up study with more than 700 participants, the authors found that social phobia has the most chronic progression and the least likelihood of recovery with a probability of 0.37 by year 12.

However, patients who did recover from social phobia had less likelihood of having a recurrence compared with other anxiety disorders.

Panic disorder without agoraphobia had the best chance of recovery with a probability of 0.82.⁸ The presence of comorbidities, such as depression, substance misuse and other anxiety disorders are associated with poor prognosis.

Only half of patients with social phobia and specific phobia will make treatment contact.

Most patients with panic disorder will make contact but even then only a third make contact in the year of onset.⁹

In a five-year prospective naturalistic study of panic disorder, the authors found that the duration of illness before treatment showed a strict relationship with long-term outcome, with patients having a lesser duration of illness at the moment of the index episode showing a better outcome.¹⁰

Section 5: Case study

Mr P was a 34-year-old IT professional who presented with anxiety symptoms. On evaluation, Mr P said that his job involved making public presentations and interacting with other professionals.

Increasingly anxious
Over the years, he had been becoming increasingly anxious about giving presentations, due to fear of embarrassing himself by saying ‘stupid things’.

He would start worrying excessively days before a presentation. He would experience palpitations and tremors.

He had been able to cope by drinking small amounts of alcohol prior to his presentations.

However, his symptoms had been increasing and he resorted to avoiding these interactions as much as possible.

It had affected his career progression and his employers were concerned.

He described himself as shy and introvert but denied having difficulties in interacting with his family or close friends.

He also denied being anxious in other situations that did not involve interaction with others or worrying excessively in general.

A diagnosis of social phobia was made. He was referred for CBT and commenced on SSRIs.

A follow-up appointment was offered for two weeks’ time.

Section 6: Evidence base

Guidelines

• Evidence-based guidelines for the pharmacological treatment of anxiety disorders: recommendations from the British Association for Psychopharmacology (BAP).www.bap.org.uk/pdfs/Anxiety_Disorder_Guidelines.pdf

BAP’s guidelines are a valuable source of information and give a good outline of management of specific anxiety disorders both in primary and secondary care.

They also suggest a scheme for exploration of anxiety disorders.

• NICE. Anxiety: management of anxiety (panic disorder, with or without agoraphobia, and generalised anxiety disorder) in adults in primary, secondary and community care. CG22. NICE, 2004, London.

Key texts

• Sadock BJ, Sadock VA, Ruiz P. Kaplan & Sadock’s Comprehensive Textbook of Psychiatry. 9th edition. Lippincott Williams and Wilkins, 2009.
• Semple D, Smyth R. Oxford Handbook of Psychiatry. 2nd edition. OUP, 2009, Oxford. This book has relevant information on psychiatric disorders, ideal for quick reference.

Curriculum
The RCGP covers this topic in statement 13 of the GP curriculum ‘Care of people with mental health problems’.

Online

• Royal College of Psychiatrists

http://rcpsych.ac.uk/mentalhealthinfoforall/problems/anxietyphobias.aspx

There is a dedicated section on patient information, self-help tips and leaflets on anxiety disorders.

• Anxiety Care

www.anxietycare.org.uk

A London-based organisation that provides help and support through an online community, as well as a helpline. They also run a mutual support and recovery group.

References
1. Somers JM, Goldner EM, Waraich P et al. Prevalence and incidence studies of anxiety disorders: A systematic review of the literature. Can J Psychiatry 2006; 51: 100-13.

2. Wittchen H U, Jacobi F. Size and burden of mental disorder in Europe: a critical review and appraisal of 27 studies. Eur Neuropsychopharmacol 2005; 15: 357-76.

3. WHO. ICD-10 classification of mental and behavioural disorders. WHO, Geneva, 1992.

4. Goldenberg IM, White K, Yonkers K et al. The infrequency of “pure culture” diagnoses among the anxiety disorders. J Clin Psychiatry 1996; 57 (11): 528-33.

5. Moffitt TE, Harrington H, Caspi A et al. Depression and generalized anxiety disorder: cumulative and sequential comorbidity in a birth cohort followed prospectively to age 32 years. Arch Gen Psychiatry 2007; 64: 651-60.

6. Grant BF, Hasin DS, Stinson FS et al. Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychol Med 2005. 35, 12; 1747-59.

7. Hunot V, Churchill R, Teixeira V et al. Psychological therapies for generalised anxiety disorder. Cochrane Database Syst Rev 2007; 1. Art. No: CD001848.

8. Bruce SE, Yonkers KA, Otto MW et al. Influence of psychiatric comorbidity on recovery and recurrence in generalized anxiety disorder, social phobia, and panic disorder: A 12-Year prospective study. Am J Psychiatry 2005; 162: 1179-87.

9. Wang PS, Berglund P, Olfson M et al. Failure and delay in initial treatment contact after first onset of mental disorders in the national comorbidity survey replication. Arch Gen Psychiatry 2005; 62: 603-13.

10. Faravelli C, Paterniti, Scarpato A. 5-Year prospective, naturalistic follow-up study of panic disorder. Compr Psychiatry 1995; 36: 271-7.

1. Aetiology

Around 10-20% of the adult population has symptoms of GORD at some stage of their lives. GORD is two to three times more common in men than in women. Its prevalence increases with age.

Obesity, smoking, pregnancy, family history, hiatus hernia and various medications (for example, tricyclic antidepressants, nitrates, calcium-channel blockers) are all associated with GORD. Certain foods can relax the lower oesophageal sphincter, including chocolate, coffee, alcohol and fatty meals.

GORD can lead to oesophagitis, but it is not very common; only around 8% of patients with GORD have moderate or severe oesophagitis. Some patients have abnormalities in their lower oesophageal sphincter which leads to reflux of their gastric contents.

2. Presentation

Common symptoms include heartburn, regurgitation and dysphagia. Atypical symptoms include chest pain, cough, hoarseness and bloating. Symptoms are classically worse when lying down or leaning forward, and improve with antacids.

It is useful to assess the impact of symptoms on the patient’s quality of life. It is also important to exclude alarm signs that may suggest a more serious underlying diagnosis. See below:

Indications for urgent referral for suspected GI cancer

• Dysphagia at any age.
• Dyspepsia at any age combined with one or more of the following:

- Weight loss.

- Proven anaemia.

- Vomiting.

• Dyspepsia in a patient aged ?55 years with at least one of the following:

- Onset of dyspepsia less than one year ago.

- Continuous symptoms since onset.

• Dyspepsia combined with at least one of the following known risk factors:

- Family history of upper GI cancer in more than two first-degree relatives.

- Barrett’s oesophagitis.

- Pernicious anaemia.

- Peptic ulcer surgery more than 20 years before.

- Known dysplasia, atrophic gastritis or intestinal metaplasia.

- Jaundice.

- Upper abdominal mass.

3. Investigations

The diagnosis of GORD is usually made by the history. The most common investigation is gastroscopy, although most patients with symptoms of GORD will have a normal gastroscopy. The degree of symptoms does not usually correlate with findings on gastroscopy.

A gastroscopy may be useful to assess the severity of oesophagitis and to exclude other pathology. Among patients who have an upper endoscopy, findings range from a normal appearance, mild erythema to severe oesophagitis with stricture formation. Acid suppressant treatment should be stopped for at least two weeks before a gastroscopy.

FBC is often performed to exclude anaemia. Manometry can be performed to determine lower oesophageal sphincter pressure and identify any oesophageal motility disorders.

Oesophageal pH monitoring may be performed in some patients. This can help to confirm the diagnosis in patients in whom the history is not clear, if they have atypical symptoms, or if an endoscopy is normal.

4. Treatment

Lifestyle modification is important, including weight loss and smoking cessation (if necessary), avoidance of certain foods (for example, chocolate, citrus juice, tomato-based products), and eating smaller meals. Eating the evening meal at least three hours before going to bed is often beneficial.

The most common medications given to patients with GORD are PPIs. However, antacids are still recommended first line. They can also be used in conjunction with other medication, for example PPIs. H2 receptor antagonists, such as ranitidine, remain a useful choice for some patients.

PPIs have been shown to be more effective than H2 receptor antagonists in relieving heartburn in patients with GORD who are treated empirically and in those with normal gastroscopy findings.²

PPIs can be given at a healing dose for one to two months, which can be reduced once symptoms improve. The lowest effective dose can then be given as maintenance treatment.

Patients should have a trial without treatment once their symptoms completely improve. The dose of the PPI is gradually reduced before stopping it.

Helicobacter pylori can be initially detected using either a carbon-13 urea breath test or a stool antigen test, or laboratory-based serology where its performance has been locally validated.1 There is currently inadequate evidence to guide whether full-dose PPI for one month or H pylori test and treat should be offered first. NICE recommends that either treatment may be tried first, with the other being offered if symptoms persist or return.

Some patients do not respond to optimal medical treatment and may be offered surgery.

Successful antireflux surgery can be more effective than medical therapy in preventing both acid and bile reflux.³

Laparoscopic fundoplication can provide satisfactory outcomes and definitive relief of acid reflux.⁴ Indications for surgery include symptoms that are not completely controlled by PPIs, presence of Barrett’s oesophagus, presence of atypical symptoms of GORD, including cough, wheezing, hoarseness, sore throat; young patients, and patients who do not want to take medication long term.

5. Complications

The risk of complications increases with longer duration and increased frequency of gastro-oesophageal symptoms. Complications of GORD include oesophagitis, gastric ulcer, anaemia, oesophageal stricture and Barrett’s oesophagus.

REFERENCES

1. NICE. Managing dyspepsia in adults in primary care. CG17; August 2004.

2. Van Pinxteren B, Sigterman KE, Bonis P et al. Short-term treatment with proton pump inhibitors, H2-receptor antagonists and prokinetics for gastro-oesophageal reflux disease-like symptoms and endoscopy negative reflux disease. Cochrane Database Syst Rev 2010; (11): CD002095.

3. Marano S, Mattacchione S, Luongo B et al. Laparoscopic Nissen-Rossetti fundoplication for gastroesophageal reflux disease patients after 2-year follow-up. J Laparoendosc Adv Surg Tech 2012; 22(4): 336-42.

4. Rosemurgy AS, Donn N, Paul H et al. Gastroesophageal reflux disease. Surg Clin North Am 2011; 91(5): 1015-29.

Uterine Fibroids are the most common tumours among the female population. The incidence of uterine fibroids increases in women with increasing age, affecting more than 30% of women aged 40 to 60 years.

The exact aetiology of uterine fibroids is not completely understood. There is evidence that fibroids are monoclonal tumours that grow from a single mutated uterine smooth muscle cell at various sites within myometrium. However, the initiating and promoting factors influencing growth of these single myometrial cells is not clearly understood.

Estrogen and progesterone hormones, along with other growth factors, have been shown to have direct influence.

Environmental factors
Environmental factors have also been shown to influence fibroid formation. Smoking appears to decrease the risk of fibroid formation and growth. This is thought to be secondary to reduction in circulating SHBG, which is a direct result of the effect of smoking on liver enzymes. This leads to a rise in the level of free estrogen, which has a mitogenic effect on fibroids.

Body weight and eating habits influence the risk of developing uterine fibroids. Uterine fibroids are two to three times more common in obese women. There is also evidence to suggest that excessive dietary intake of beef and ham is associated with increased risk of developing fibroids. In contrast, a diet rich in green vegetables decreases the risk. A number of animal studies have also shown an inhibitory effect of green tea extracts on uterine fibroids.

Despite these findings, there is no evidence that dietary changes, following presentation and diagnosis of uterine fibroids, would have any influence on a patient’s symptoms.¹
In addition, clear differences in disease prevalence in different racial groups, in particular in women of African origin, further highlight an underlying poorly understood genetic predisposition to the condition.

Genetic factors
Genetic and hereditary causes are being considered and several epidemiological findings indicate considerable genetic influence, especially for early onset cases. Chromosomal abnormalities are present in nearly 50% of fibroids and mutations in the MED12 gene have been documented in 70% of fibroids. However, it is interesting that when multiple fibroids are present, unrelated genetic defects can be detected, adding to the complexity of genetic predisposition. Nevertheless, it is well established that first-degree relatives have a 2.5-fold increased risk and this can be a nearly sixfold increased risk in early onset cases.

Section 2: Making the diagnosis

Fibroids are round, well circumscribed, solid nodules with variable size, from microscopic to huge masses filling the whole abdominal cavity (see main image above). Generally, fibroids the size of a grapefruit or bigger can be felt by the patient and are readily noted on bimanual pelvic palpation.

Fibroids are often asymptomatic. However, larger fibroids could cause many symptoms, depending on their size and location.

Key symptoms

Important symptoms include heavy or painful periods, abdominal discomfort and bloating, backache, painful defecation, urinary frequency or retention.

In some patients, fibroids can result in dyspareunia or infertility, depending on their position. Submucous fibroids are thought to interfere with the implantation process and larger fibroids can block the fallopian tubes.

During pregnancy, fibroids may be the cause of miscarriage, premature labour, pain or malpresentation of the fetus. Cervical and lower uterine fibroids can also interfere with labour and make caesarean section delivery challenging. Rarely, fibroids are located in the round ligament, broad ligament, or uterosacral ligament of the uterus, making differential diagnosis from an ovarian lesion difficult.

Imaging modalities
The diagnosis of fibroids is primarily based on imaging, either ultrasound or MRI. In both modalities, fibroids have characteristic features that are easy to diagnose. However, secondary changes can sometimes develop in fibroids (haemorrhage, necrosis, calcification or cystic changes) that can make diagnosis difficult, in particular on ultrasound scan.

Transvaginal ultrasound scan (TVS) is more reliable than abdominal ultrasound in assessing uterine fibroids, especially in obese patients. The readily accessible and cost-effective aspect of TVS has made it the preferred first-line investigation in patients with suspected uterine fibroids.

MRI is a costly but powerful investigatory tool that is particularly useful in establishing the exact position, characteristics and number of fibroids, and their associated relationship with the adjacent viscera.

MRI is especially useful in patients with large fibroids or pedunculated fibroids that can be disguised as an adnexal mass. In addition, in patients with large fibroids, the ovaries are lifted out of the pelvis and may not be readily identifiable with ultrasound. This is easily overcome with MRI.

As yet, there are no imaging modalities that can distinguish benign uterine fibroids from malignant uterine leiomyosarcoma. Fast growth, in particular after menopause, may raise the index of suspicion that the lesion might be a sarcoma.

However, such observation, although it appears intuitively reliable, is not supported by the available data in the literature, partly due to the rarity of leiomyosarcoma.²

Section 3: Managing the condition

Medical treatment
A number of medications are used to treat the symptoms of fibroids, including NSAIDs for pain, oral contraceptives to reduce uterine bleeding and iron supplements for anaemia.

The levonorgestrel intrauterine system (IUS) effectively reduces menstrual blood flow, even in patients with fibroids; there is evidence to suggest it may induce a degree of regression. However, spontaneous expulsion is more frequent in patients with fibroids.

Danazol provides effective symptomatic relief and reduces fibroid size, but is rarely used because of side-effects.

Gonadotropin-releasing hormone (GnRH) analogues can cause regression by decreasing circulating estrogen. Owing to their side-effects and the risk of osteoporosis, they are often used temporarily, before surgery, to shrink fibroids. GnRH analogues can be considered in conjunction with add-back HRT to alleviate side-effects.

Growing evidence suggests progesterone plays a key part in fibroid development and growth. Progesterone antagonists such as mifepristone have been shown to reduce the size of uterine fibroids, but significant side-effects have been noted.

Research is focused on a selective progesterone receptor modulator (asoprisnil), which it is hoped will be as effective as progesterone antagonists but without major side-effects.³

Uterine artery embolisation

Uterine artery embolisation (UAE) is a safe, effective and well-established radiological technique used in the management of symptomatic fibroids as an alternative to myomectomy. It is advocated in women who have completed their family.

UAE can significantly alleviate pain, menstrual loss and pressure effects from fibroids. The average decrease in fibroid volume is about 40%, although some report up to 70%.

This is similar to what is often achieved with GnRH agonists, except that the fibroid does not regrow after cessation of treatment. Furthermore, shrinkage tends to continue many months after UAE; with GnRH agonists it is limited to the first three to six months.

Complications with UAE are generally uncommon, but include adverse reactions to the contrast media, haematoma, thrombosis or pseudo-aneurysm. Vaginal discharge and abdominal pain are common following the procedure but usually resolve in a few days. The vaginal discharge can become chronic and foul-smelling, due to fibroid expulsion, and surgical evacuation of the uterus may be required.

Post-embolisation syndrome may occur in a small number of patients. Patients present with pain, flu-like illness, mild pyrexia and nausea in association with raised inflammatory markers. If these symptoms persist, infection must be suspected and promptly treated.⁴

Despite good shortand medium-term outcomes, a significant number of women will require hysterectomy or repeat embolisation. The HOPEFUL trial showed that 23% of women required further intervention following UAE at a mean follow-up of 4.6 years.⁵

There is also an association between UAE and ovarian failure, hence it is contraindicated in patients who wish to become pregnant. In addition, there is evidence to suggest that UAE is associated with spontaneous abortion, abnormal placentation, preterm delivery and postpartum haemorrhage. It appears these complications are more common after UAE than after myomectomy.⁵

There are a few reported case series from advanced laparoscopic surgery centres on uterine artery occlusion in the management of fibroid- related symptoms. The principle is similar to UAE but occludes uterine arteries externally using clips, ligatures or diathermy.

Short-term follow-up data on this technique are promising but the need for general anaesthesia and surgical intervention make it more applicable to centres with no access to UAE expertise or resources.

High-intensity focused ultrasound
High-intensity focused ultrasound is a non-invasive thermo-ablative technique that focuses ultrasound waves on fibroid tissue, raising the temperature within the diseased tissue and destroying it. The procedure has been enhanced by the use of MRI to guide it (MR-guided focused ultrasound).

Data on this new technique are promising, although the reduction in size of fibroids seems modest compared with other modalities and importantly, only a small number of fibroids can be treated per session. Hence, patients with multiple fibroids are either unsuitable or need multiple treatments.⁶

Myomectomy
Myomectomy is usually recommended in patients who wish to preserve their fertility and have not responded to medical treatment. It can also be considered in a patient who strongly wishes to retain her uterus.

This is most often done by laparotomy, but increasingly via laparoscopy or hysteroscopic resection. There is a small associated risk of hysterectomy, most often due to excessive intraoperative bleeding. Myomectomy is also associated with a risk of postoperative adhesion formation and recurrence.

Hysterectomy
Hysterectomy remains a common option in patients with fibroids who have completed their family and failed to respond to medical management.

Endometrial ablation
Endometrial ablation can be considered in selected patients with no fertility concerns. It is suitable for those primarily with menstrual bleeding problems. The extent of endometrial cavity distortion is important in the selection of suitable patients.

Section 4: Prognosis

Fibroids are dependent on estrogen and progesterone to grow and they tend to shrink after menopause.

There have therefore been concerns about whether HRT should be prescribed, particularly in perimenopausal patients who are experiencing heavy menstrual bleeding.

Prescribing HRT
Very few studies have examined the question of prescribing HRT. It appears that generally, the increase in fibroid size is not significant and should not have a major influence on symptoms.

However, the best course of action is to monitor the size of the fibroids and the patient’s symptoms following the introduction of HRT. Tibolone, a synthetic steroid with weak estrogenic effects, may be considered as an alternative.

Malignancy
The malignant version of a fibroid is extremely uncommon and is termed a leiomyosarcoma. The incidence of malignant transformation of fibroids is difficult to determine because many women have asymptomatic fibroids and are unaware of their presence.

However, the incidence of uterine leiomyosarcoma is low, in particular in young patients in their reproductive years.7

Section 5: Case study

A 42-year-old nulliparous patient of African descent was admitted to the intensive care unit with septicaemia following multiple dental extractions. She was found to be in renal failure, with a grossly distended abdomen due to a large 36-week size solid mass.

CT images revealed a large uterine mass with associated bilateral hydronephrosis and an atrophic, non-functioning left kidney, probably due to severe hydronephrosis on that side.

In addition, a thrombus was noted within her left common iliac vein as the result of compression by the uterine mass. She reported no menstrual problems and no bowel or urinary symptoms. However, she had noted worsening abdominal distension over the preceding 18 months.

Further MRI suggested very large uterine fibroids with heterogeneous features compressing adjacent viscera. The possibility of leiosarcomatous changes was therefore raised.

Further review
Her images were reviewed in the regional cancer meeting and the suggestions confirmed by the lead cancer radiologist. UAE was ruled out due to pelvic vein thrombosis and raised suspicion of malignancy. Her sepsis resolved and she was transferred to the cancer unit for hysterectomy, following insertion of an inferior vena cava filter.

The patient underwent major laparotomy; the fibroids proved to be bilateral giant ovarian fibromas, with no evidence of malignancy on histological assessment. Her uterus appeared to contain a few small fibroids and was preserved.

The differential diagnosis of ovarian fibroma and uterine fibroids, in particular pedunculated fibroids, can be exceedingly difficult on imaging.

CA125 is of limited value; it would be moderately elevated in both cases. However, absence of menstrual symptoms or highly elevated CA125 could be more suggestive of ovarian pathology.

Section 6: Evidence base

Clinical trials

• A multicentre retrospective cohort study comparing hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids (HOPEFUL study): main results on medium-term safety and efficacy.

The largest observational study comparing the results of UAE carried out in large units throughout the UK and hysterectomy.

According to these researchers, UAE appears to be at least as safe as surgical treatment and the associated complication rates compare favourably with those for hysterectomy.

• Randomised comparison of uterine artery embolisation (UAE) with surgical treatment in patients with symptomatic uterine fibroids (REST trial): 5-year results. BJOG 2011; 118: 936-44.

This trial demonstrates no significant differences between the two treatment modalities.

Symptom score reduction and patient satisfaction with either treatment were very high. Rates of adverse events were also similar in both groups.

However, the five-year intervention rate for treatment failure or complications was 32% for UAE and only 4% in the surgical arm.

Guidelines

• NICE. Heavy menstrual bleeding. CG44. NICE, 2007, London.www.guidance.nice.org.uk/CG44/NICEGuidance/pdf/English

Key texts

• Stewart EA. Uterine fibroids. Lancet 2001; 357: 293-8.

A comprehensive review covering the epidemiology, aetiology, pathogenesis and management of uterine fibroids.

• Lumsden MA. Modern management of fibroids. Obstet Gynaecol Reprod Med 2010; 20: 82-6.

A well-written review article on the management of uterine fibroids, with particular emphasis on the role of UAE in their management.

• Uterine artery embolization for symptomatic uterine fibroids. Cochrane Database Syst Rev 2006; (1): CD005073.

Curriculum
This topic falls under section 10.1 of the RCGP curriculum, Women’s Health.

References
1. Stewart EA. Uterine fibroids. Lancet 2001; 357: 293-8.

2. Parker WH. Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril 2007; 87(4): 725-36.

3. Wilkens J, Chwalisz K, Han C et al. Effects of the selective progesterone receptor modulator asoprisnil on uterine artery blood flow, ovarian activity and clinical symptoms in patients with uterine leiomyomata scheduled for hysterectomy. J Clin Endocrinol Metab 2008; 93: 4664-71.

4. Lumsden MA. Embolization versus myomectomy versus hysterectomy: which is best, when? Hum Reprod 2002; 17: 253-9.

5. Dutton S, Hirst A, McPherson K et al. A UK multicentre retrospective cohort study comparing hysterectomy and uterine artery embolisation for the treatment of symptomatic uterine fibroids (HOPEFUL study): main results on medium-term safety and efficacy. BJOG 2007; 114: 1340-51.

6. Zaher S, Gedroyc WM, Regan L. Patient suitability for magnetic resonance guided focused ultrasound surgery of uterine fibroids. Eur J Obstet Gynecol Reprod Biol 2009; 143(2): 98-102.

7. Amant F, Coosemans A, Debiec-Rychter M et al. Clinical management of uterine sarcomas. Lancet Oncol 2009; 10: 1188-98.

To learn about fibroids in pregnancy: Fibroid in Pregnancy