Download Diabetes Mellitus

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Diabetes Mellitus
Diabetes mellitus is a relatively common disorder which is of major aeromedical concern. It is regularly
screened for by urine testing at routine medical examinations and in some organisations by a fasting
glucose estimation.
DIAGNOSIS:
The finding of glycosuria should prompt a fasting blood glucose estimation. The precise diagnostic
criteria for diabetes and impaired glucose tolerance are subject to small variations with time and
between national advisory bodies, and the cut off points are to some extent arbitrary, given the
continuous nature of the spectrum of glucose intolerance. The 2006 WHO criteria are as follows:
Because of the considerable implications that the diagnosis of diabetes mellitus has for the career of
professional aircrew, great care should be taken to perform a glucose tolerance test under standardised
conditions. The subject should consume a diet of adequate carbohydrate content (> 250 grams/day) for 3
days prior to the test and then be fasted overnight. Blood for fasting glucose should be collected prior to
the administration of 75g of glucose in 300 ml of water and a further blood sample collected 2 hours later.
For subject who fit into the impaired glucose tolerance category, regular follow up is essential as they
have a 5% per annum risk of becoming frankly diabetic, and carry an increased cardiovascular disease
risk. An annual glucose tolerance test for such individuals is advised, but otherwise they are permitted to
fly with an unrestricted category.
AEROMEDICAL CONCERNS
Diabetes Mellitus is a major risk factor for cardiovascular disease, and the cardiovascular mortality
amongst diabetics is increased by a factor of at least 2. The all cause mortality relative risk is 1.5 - 2.0
compared to age and sex matched controls. The microvascular complications of diabetes mellitus have
implications for aircrew, with retinopathy, neuropathy and nephropathy being commonly encountered.
It is important to note that all these complications are equally prevalent among those the insulin
dependent (type 1) and the non-insulin dependent (type 2) forms of the disease. A major aeromedical
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concern in diabetes mellitus relates to the high incidence of hypoglycaemia in patients requiring
pharmacological therapy. The annual incidence of significant hypoglycaemia in insulin using diabetics,
defined as requiring the assistance of another person, is around 10%, and the incidence is around 30%
for milder hypoglycaemic episodes. There is evidence to suggest that mild hypoglycaemia is associated
with decrements of cognitive function and decision making ability at levels before clinical symptoms are
apparent to the patient, and these abnormalities can persist for some time after correction of
hypoglycaemia. The risk of hypoglycaemia in type 2 diabetics treated with sulphonylureas varies widely,
with different series reporting rates of 2-20% per annum, but no agents of this class appear to be totally
free of this potential complication. The only biguanide in use in the Western world, metformin, is not
reported as causing hypoglycaemia, and this is compatible with what is understood of its mode of action.
TREATMENT & AIRCREW DISPOSAL
In type 2 diabetics, dietary modification, exercise and significant weight reduction may be compatible
with good control, acceptable 24 hour blood glucose profiles, and even a return toward normal of the
glucose tolerance test. Such an approach may allow a return to flying duties, quite possibly without
limitations, but regular reviews at intervals not exceeding 6 months would be required, when objective
evidence of diabetic control should be sought with HBA1c levels and capillary blood glucose profiles. At
such reviews weight should be monitored and checks be made for microvascular complications and
cardiovascular disease, as well as reviewing the patient for other cardiovascular risk factors (particularly
hypertension). There is a strong case for performing exercise ECGs on all diabetic aviators at yearly
intervals, particularly beyond the age of 40 years (required by UK CAA). The pharmacological agents
permitted in the flying environment for diabetic control are limited, but the range is steadily expanding.
While the intestinal alpha-1glucosidase inhibitor, acarbose, is acceptable, gastrointestinal side effects are
common and it is not popular with aircrew. Metformin is permitted as pharmacological therapy for type
2 diabetics who fail to respond to diet and lifestyle changes alone, has significant cardio-protective effects
in diabetics, and is not associated with hypoglycaemia. It is acceptable in professional aviators with a
multi-crew restriction, but even that limitation is under review by the CAA. The thiazolidinediones, or
‘glitazones’, are primarily recommended for use in combination with another oral hypoglycaemic agent
and in combination with metformin these drugs were initially not considered acceptable in the flight
environment because of concerns over the possible risk of hypoglycaemia. However, with increasing
experience and confidence, this combination is now permitted for restricted flying duties, in a multi-crew
environment. Glitazones may also be considered for use as sole therapy in patients who suffer
unacceptable side effects with metformin (see table). The risk of hypoglycaemia is considered
unacceptable with all the currently available sulphonylurea drugs and none of the other classes of
emerging agents is as yet considered acceptable in aircrew. However, the development of the incretinbased agents has been an exciting therapeutic progression and the use of DDP-4 inhibitors (the ‘glyptins’)
in the flying environment are under active review.
Flying categories for type 2 diabetics requiring drug therapy would usually exclude high performance
aircraft, and involve restriction to multi-crew aircraft types. A further concern in military flying is the
effect of military operations on diabetic control with irregular working hours, lack of access to normal
dietary sources, and extreme emotional and physical stress all tending to disturb the normal equilibrium.
Insulin dependent diabetes is widely considered a complete bar to all types of flying, the risk of
hypoglycaemia being considered incompatible with flight deck duties. No level of HBA1c in type 1
diabetics treated with insulin has been shown to be associated both with adequate diabetic control
(particularly important now that the risk of complications has been clearly demonstrated to be related to
blood glucose levels) and freedom from significant risks of hypoglycaemia. This point of view has been
contested in the USA and Canada, where several hundred private pilots have now been licensed to fly
with onerous safeguards in place to (hopefully) preserve flight safety. These pilots have had to
demonstrate good diabetic control and absence of complications, together with freedom from
hypoglycaemic episodes for at least one year.
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Diet
alone;
glitazones
Fit all classes
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Diagnosis of Diabetes Mellitus
Temporarily Unfit
Insulin – permanently unfit
acarbose; Metformin +/- glitazone
Suphonylureas
Class 1 (OML) / Class 2 Unfit Class 1 / Class 2 (OSL)
unrestricted
AIRCREW SELECTION
A history of any form of diabetes is unacceptable for aircrew selection, and in the Royal Air Force a strong
family history (2 first degree relatives with diabetes) would be regarded as an indication for considering
a glucose tolerance test prior to selection.
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Thyroid Disease
Thyroid diseases are the second most commonly encountered endocrine disorders and are important to
identify as abnormalities of thyroid function can have significant effects on judgement, psychomotor
functions, mood, reaction times and many other facets of human physiology and psychology. What is
more, they are usually eminently treatable, with a subsequent return to full aircrew duties being possible.
THYROID FUNCTION TESTS
Normal control over thyroid function is dependent upon a negative feedback control system, which starts
with synthesis of thyrotrophin releasing hormone by the hypothalamus. This acts within the anterior
pituitary to liberate thyroid stimulating hormone (TSH) which in turn influences the thyroid gland to
increase its output of thyroxine (T4) and tri-iodothyronine (T3). These hormones circulate in plasma
bound to protein, with only small amounts of free T4 and even smaller amounts of free T3 being present.
Within peripheral tissues a proportion of T4 is converted to T3 which is the most active thyroid hormone.
Plasma T4 and T3 exert a negative feedback influence on the anterior pituitary release of TSH, via the
hypothalamus.
Radioimmuno assays of TSH, free T4 and free T3 nowadays provide a reliable and accurate biochemical
assessment of thyroid function in most circumstances. The TSH level is the most reliable single test, is
both sensitive and specific, being depressed in situations of excessive thyroid activity, and elevated in
hypothyroidism. However it needs to be appreciated that TSH levels can be altered in acute and chronic
disease states when misleading results can be obtained. Free T4 is an accurate and useful second line
measurement of thyroid function, but can also be influenced by drugs and disease.
HYPERTHYROIDISM
This is a syndrome resulting from excess circulating T4 and/or T3. The most common cause is Graves’s
disease, with other causes including toxic multinodular goitre, solitary toxic nodule, and acute thyroiditis.
The hyperthyroid syndrome is characterised by weight loss with a good appetite, fatigue, muscular
weakness and insomnia, sweating and heat intolerance, palpitations, tachycardia and is occasionally
complicated by atrial fibrillation. The patients often exhibit agitation and tremor, with emotional lability,
and diarrhoea is common, as is oligomenorrhoea in females. Graves’ disease is commoner in females in a
ratio of 5:1, and is an immunologically mediated disorder in which IgG antibodies (thyroid stimulating
antibodies) bind to TSH receptors within the thyroid, while other related antibodies act on retro-orbital
tissues. Such patients exhibit hyperthyroidism, usually with a diffuse goitre, often with a bruit over the
gland. 50% will show an ophthalamopathy with proptosis and impairment of extra-ocular muscle
function. The disease is a remitting and relapsing disorder whose acute symptoms can be eased by beta
blockers, but the definitive therapeutic modalities include antithyroid drugs, subtotal or total surgical
thyroidectomy, or radio-active iodine therapy. The aeromedical concerns of the hyperthyroid state are
multiple and self evident from the above list of possible symptoms, but may also include fatigue, poor
concentration and impaired judgement.
Drug treatment consists of using antithyroid compounds, carbimazole and propylthiouracil being the
most frequently prescribed in this country, for a period of 18 months to 2 years. These drugs not only
block the synthesis of thyroxine within the thyroid gland, but also appear to exert an immunological
effect resulting in falling titres of thyroid stimulating antibodies. Traditionally the drug dose is titrated
against thyroid function, but an increasingly favoured approach is to maintain full doses of the thyroid
blocking compound, avoiding hypothyroidism by the addition of oral L-thyroxine supplements as
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required. Relapse rates after medical treatment are high, around 60-70% but may be lower with the
second of these approaches, where a greater suppression of antibody levels appears to be achieved.
Relapse would be an indication to consider radio-iodine therapy, as would drug side effects such as skin
rashes or evidence of bone marrow aplasia.
Radioactive iodine therapy has much to commend it from both the general clinical and aviation medicine
view points. After initial control of the acute hyperthyroid estate with anti-thyroid drugs, iodine 131
treatment usually results in a permanent remission of the disease, but with a very significant chance of
the subsequent development of hypothyroidism. The treatment is simple and quick, and appears to be
remarkably safe. Although initially this approach was only offered to more mature adults (over 40 years)
many centres are now offering radioactive iodine therapy to much younger individuals. Those treated
with this modality require regular long term follow up of their thyroid function, with replacement Lthyroxine being provided when, and if, they develop hypothyroidism, as indicated by a rising TSH level.
Subtotal or total thyroidectomy is less frequently used these days, except for young people who have
relapsed after medical treatment, and do not wish radioactive iodine treatment. Complications include
hypoparathyroidism (usually only temporary) and recurrent laryngeal nerve damage.
HYPOTHYROIDISM
This is a syndrome resulting from reduced circulating levels of T4 and T3, and is most commonly caused
by autoimmune thyroiditis or Hashimoto’s disease. It can also be iatrogenic, induced by surgery or iodine
131 treatment, and more rarely may be related to iodine deficiency, other drug treatment, or
dyshormonogenisis.
The disorder is characterised by fatigue, weight gain and cold intolerance, with patients complaining of
dry skin, hair loss, constipation and muscular stiffness. It is complicated by hyperlipidaemia, the rapid
evolution of ischaemic heart disease, depression, vocal changes, and carpal tunnel syndrome. Clinical
signs include the characteristic skin and facial changes, bradycardia and a delay in the relaxation phase of
tendon jerks. In Hashimoto’s disease there is usually a firm diffuse goitre without a bruit, and there is an
association with other autoimmune disorders. Thyroid antibody titres are substantially elevated.
Treatment consists of replacement L-thyroxine, increasing the dose slowly until clinical and biochemical
evidence of a return to the euthyroid state is achieved. In the long term a regular monitoring with clinical
assessment and TSH levels is required, as drug compliance is a significant problem in a minority.
AEROMEDICAL DISPOSAL
Abnormalities of thyroid function should initially result in subjects being made unfit for all aircrew
duties. Hyperthyroid subjects can be considered for limited flying duties (multicrew) once they are
euthyroid on treatment, but usually not before 4 – 6 months, and will require close monitoring. After one
year those with stable thyroid function can be considered for unrestricted flying duties, but with
indefinite medical follow up. Those subjects with treated hypothyroidism can be considered for a return
to full flying duties once a euthyroid state is established on replacement therapy, provided all symptoms
and complications of the disorder are resolved.
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ANAEMIA
AEROMEDICAL CONCERNS
Decreased oxygen carrying capacity of the blood leads to an increased cardiac output for a given work
load. In turn, there is a decreased effort tolerance and sub-clinical cardiovascular problems may be
unmasked. The presence of anaemia may also be an indicator of a wide variety of underlying disease
processes.
CLASSIFICATION
Nutritional
- iron
- vitamin B12
- folic acid
Haemolytic
- inherited
- acquired
- red cell membrane defects
- abnormal haemoglobin
- red cell enzyme abnormalities
- immune
- non-immune
Bone marrow - aplastic
- suppressed by chronic disease
- infiltration
SPECIFIC EXAMPLES
Iron deficiency
- in males consider GI blood loss, diet and malabsorption. Worldwide,
intestinal parasites are the commonest cause.
- in females, consider menstrual losses in addition
Runners’ anaemia
- commonly a physiological adaptation associated with increased red cell
mass and even greater increase in plasma volume
- ? traumatic haemolysis or traumatic blood loss - probably not significant
Beta-thalassaemia trait
- such individuals usually have only a modest stable anaemia, and a normal
exercise tolerance. They may be fit for aircrew selection but each case
will have to be decided on the basis of individual assessment.
Congenital spherocytosis - when treated with splenectomy in childhood, may maintain near normal
haemoglobin levels. However, the susceptibility of splenectomised subjects to
certain infections and particularly to malaria, may have significant
implications for military aircrew selection.
Sickle cell trait
©Prof. Anthony Batchelor
- contentious issue. Risk of precipitating sickling has been considered to
be associated with fever, dehydration, immobility and reduced ambient
inspired oxygen tension. In practice, flying duties do not seem to present a
significant risk to fit young individuals, and most organisations (including RAF)
have stopped screening.
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ANAEMIA AND AEROMEDICAL DISPOSAL
Aircrew selection
- bar to flying training
- possible reconsideration after investigation
Trained aircrew
- symptomatic or significant anaemia (Hb < 12 g/dl) - immediate grounding;
return to flying depends upon finding a curable cause
- mild anaemia - depends on cause and individual assessment
Aeromedical evacuation
©Prof. Anthony Batchelor
- acute anaemia; Hb > 9-10g/dl (but dependent on cause and other conditions)
- chronic anaemia; Hb ? > 7 g/dl
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Air Travel and Venous Thrombosis
Venous thrombo-embolism (VTE)
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Incidence 1 in 1,000/annum in developed counties
Increases with age (1 in 100,000 in childhood to 1% in old age)
Virchow’ triad –
– Stasis of blood
– Changes in blood
– Changes in vessel wall
Genetic and acquired
Travellers’ Thrombosis
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Simpson 1940: increased incidence of DVT (deckchair thrombosis)
1954 Homans: venous thrombosis and prolonged sitting (2 car; 2 flying; 1in a theatre)
1977 Symington & Stack “economy class syndrome”
1984 Cruickshank et al “economy class syndrome”
1996 Eschwege & Robert: increased incidence of DVT in commuters caught up in Paris bus strike
1998 Mercer & Brown: 134 cases of PE - 50% had travelled for > 4 hours in previous 31 days
1999 Ferrari et al: 160 cases of VTE - 39 had recently travelled (9 flying; 28 car; 2 train)
Kesteven & Robinson: 86 pts who developed VTE within 28 days of flying
• 72% had at least one risk factor prior to flight
• 87% occurred after return trips or after very long trips
• only 2% has no risk factors and no history of a return journey
• 92% developed symptoms within 96 hours of flight
Kraaijenhagen - 788 pts with VTE; unable to demonstrate association with air travel versus controls
ten Wolde et al - 198 pts; no association with travel of > 3-4 hrs
Dimberg World Bank study - no increase in VTE among frequent travellers compared to nontravelling controls
VTE and Coagulation Abnormalities
•
Thrombophilia
– Deficiencies of proteins C & S, antithrombin (rare – increase risk ten fold)
– Factor V Leiden
• present in 5% of the white population
• present in 20% of those with VTE
– Prothrombin 20210A present in 2% population; 6% with VTE
– Factor VIII levels > 150% of normal in 11%; but 25% with VTE
– Homocysteine > 18.5 micro mol/l in 5%; but 10% in those with VTE:
risk x 2.5 ( > 20 micromol/l risk x 3-4)
VTE and Risk Interaction
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Gene – gene interaction
Gene – environment interaction
– Baseline female VTE risk 0.8 per 10,000/year
– Risk for females on OCP = 3.0 per 10,000/year (relative risk 3.7)
– Risk females + factor V Leiden = 5.7 per 10,000/year (relative risk 6.9)
– Risk females + factor V Leiden + OCP = 28.5 per 10,000/year (relative risk 34.7)
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Risks Peculiar to Flying?
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hypoxia ) - but no experimental evidence (see RAF CAM/ Leicester University study!)
hypobaria ) and consider professional aircrew (no XS risk) and populations living at altitude
dehydration – mucosal dryness, but no significant overall fluid loss
alcohol – leading to diuresis, somnolence and immobility?
air quality – contentious, but no evidence for adverse influences after major studies
fluid retention
immobility
posture
Patrick Kesteven - 2001
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Fixed population of 650,000 (Newcastle)
all cases of VTE presenting to hospital
1,250 over a two year period
only 47 (3.8%) had made a journey of > 100 miles in the previous 4 weeks
– 60% by air; 36% by road; 4% by rail
– at least one medical risk factor was present in all but three of the 47
VTE incidence in NE England: 1 in 27,660 per annum
VTE – models of risk:
•
Cumulative risk
– baseline risk
– variable (age)
– fixed (coagulation abnormality)
– added factor (eg OCP)
– intercurrent event (eg. trauma,
immobility etc)
Rosendaal Lancet 1999;353:1167
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VTE and Flying Risk Strategy
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Mildly increased risk
– age > 40 years
– obesity
– minor surgery within 3 days
– active inflammatory disease
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Moderately increased risk
(Advice as above; consult GP;
– heart failure
consider graduated support stockings; not aspirin!)
– recent MI (within 6/52)
– oestrogen therapy
– pregnancy/postnatal
– lower limb trauma (within 6/52)
– polycythaemia
– paraplegia
•
High level risk
(Advice as above; consult GP;
– previous VTE
graduated compression stockings;
– known thrombophilia
consider low molecular weight heparin)
– recent major surgery (within 6/52)
– previous CVA
– malignancy
– family history of VTE
©Prof. Anthony Batchelor
(General advice – hydration, mobility;
consider support socks/stockings)
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GASTROINTESTINAL DISEASE
(NB – the notes from this point on have not all been completely revised since 2004/5. They are included for
interest, but should be read in conjunction with Ed 4 of Ernsting and hand outs from relevant lecturers)
Gastrointestinal disorders are common within the age group represented by flying personnel, and acute
gastroenteritis has repeatedly been reported as being the commonest cause of sudden in flight
incapacitation of aircrew.
TRAVELLERS’ DIARRHOEA
In excess of 1000 million people undertake international travel each year and of those over 10% travel
from industrialised to developing countries. Of the latter group acute episodes of diarrhoea are
exceedingly common, with reported rates varying from 20-50%. Most of these attacks are self limiting
and harmless but nevertheless they can interfere with holiday plans, can disrupt a business trip, and they
can have significant economic implications to host nations. Equally such attacks can have very significant
implications for military operations and for the crew of civil airline operations.
Aetiology
It is now well established that the aetiology of travellers’ diarrhoea is infective, with pathogens being
demonstrated in well over 80% of subjects. The pattern of these pathogens is closely related to the
pattern that is endemic in the host country, and is the same spectrum of enteropathogens that cause
infantile diarrhoea in these countries. Like the infants, the visitors have low resistance and high
susceptibility. By far the commonest pathogen implicated on a world wide basis is enterotoxigenic E coli,
accounting for some 40% of cases, but Shigella, Campylobacter and Salmonella are frequently
represented, together with Protozoa such as Giardia lamblia, Cryptosporidium parvum, and Entamoeba
histolytica. Further protozoan infective agents are discovered at regular intervals, and about 10% of
cases are due to viruses, the rota virus and the norwalk viruses being most commonly implicated.
Transmission
Transmission is via contaminated food and water. It must be remembered that ice is only frozen water
and can be an unsuspected source of infection, and that chlorination of swimming pool water may not be
effective in eliminating protozoal cysts.
Clinical Features
The attacks of diarrhoea start most commonly on the third day and usually resolve spontaneously within
2-4 days. More protracted symptoms, lasting for longer than one month, occur in only 1-2% of the
population involved. In most cases the illness is mild, with bowel actions not exceeding 6 per day, but
abdominal cramps together with nausea and vomiting lead to significant short term morbidity and
disability. Up to 20% of sufferers will have fever or bloody diarrhoea suggestive of enteroinvasive
disease.
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Prevention
In planning a strategy for prevention of traveller’s diarrhoea it is important to assess the risks to the
health of the individual, the effects of possible incapacitation to the mission on which the individual is
involved, and the risks within the country of destination. Individuals at high risk of infection or from
severe consequences of such infection, include those aged less than 6 years, those with reduced gastric
acidity (gastric surgery, acid suppressing drugs) and those with immuno-deficiency disorders. Subjects
with chronic inflammatory bowel disease may also be at increased risk of relapse. Prevention is firstly
based upon avoiding the enteropathogen. Travellers are advised to avoid uncooked or unpeeled food, ice
cubes and tap water, and should be aware of the risks of ingesting water in swimming pools, lakes, and
even sea water near sewage effluent points. Hot food should be served at a temperature greater than
65% centigrade and flight crews should be advised to choose different items from restaurant menus. For
subjects at high personal risk, or for those deemed to be on missions of critical importance to military
operations, political or business matters etc, in whom sudden illness could have far reaching
consequences, antimicrobial chemoprophylaxis should be considered. There is no doubt that this
approach is highly effective, with the 4-fluoroquinolone drugs being the most effective. The possibility of
encouraging drug resistant strains remains a controversial discussion point. Non-antibiotic prophylaxis
with bismuth subsalicylate is moderately effective, but the consumption of live yoghurt (infected with
lactobacillus) has not been shown to have any significant effect.
Treatment
The treatment is the therapy of acute gastroenteritis, with replacement of fluid and electrolyte loss being
fundamental. Glucose/electrolyte solutions are ideal if available, but if not a high oral fluid intake using
salty soups and fruit juices can be most effective, and can be supplemented by complex carbohydrate
sources such as rice, bread and potatoes. Antimotility agents such as loperamide provide useful symptom
relief, but should be avoided in those with evidence of dysentery. The use of antibiotics is controversial
though effective, but is indicated for specific infections such as shigella, typhoid and amoebiasis. One
study of military personnel on jungle training exercises has shown a single dose of ciprofloxacin 500 mgs
to be exceedingly effective in reducing the duration of diarrhoea, the number of fluid stools passed, and in
promoting an early return to fighting fitness.
Aircrew should not fly for between 24 and 48 hours after symptoms have resolved, depending on
operational need, thus allowing time for restoration of fluid and electrolyte equilibrium.
PEPTIC ULCER DISEASE
Peptic ulcer disease remains common in the United Kingdom with 4,111 deaths in the United Kingdom in
1996 having been certified as due to this cause. At that time it was the tenth commonest cause of death,
slightly commoner than road traffic accidents, and the death rate from peptic ulcer has risen over the past
20 years. Much of this mortality, however, does occur in an increasingly elderly population, but peptic
ulcer disease results in 40,000 hospital admissions per year and is estimated to cost the NHS £50 million.
Duodenal Ulcer
Epidemiology
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This disorder has a remitting/relapsing natural history and is commonest in young males. The incidence
is falling in men, but stable in women and duodenal ulcer is substantially commoner than gastric ulcer in
males under 40 years. A genetic component to the aetiology is indicated by the increased history
amongst first degree relatives and the increased incidence in blood group ‘O’ individuals, and nonsecretors of blood group antigens. Non-steroidal anti-inflammatory drugs account for a small percentage
of DU’s, and are associated with complications of duodenal ulcers. Over 96% of duodenal ulcer disease is
now known to be associated with a Helicobacter pylori gastritis. This infection appears to be an essential
component of the cocktail of factors required before duodenal ulceration can occur, and eradication of the
organism is associated with a dramatic reduction in relapse rate.
Clinical Features
The symptoms of localised epigastric pain eased by food, or alkalis, often waking the patient at night, and
occurring in a cyclical pattern of remissions and relapses, is well known. However it is important to
appreciate that atypical symptom patterns are common. The diagnosis is most satisfactorily made by
endoscopy particularly in those with distorted duodenal caps from previous ulcer disease, and the
procedure permits biopsy for Helicobacter pylori infection to be carried out at the same time.
Management
The management of duodenal ulcer disease was revolutionised in the late 1970’s with the introduction of
H2 receptor antangonists. For the first time drugs were available which produced acid suppression
which was adequate to allow prompt symptom relief, and high ulcer healing rates. However, it rapidly
became apparent that intervention with such agents did not change the natural history of the disease, and
cessation of therapy was associated with a very high relapse rate of 60-80% per year. The concept of
maintenance therapy with low dose H2 receptor antangonists was then introduced and this proved to be
an effective strategy, lowering the relapse rate to 20-30% per annum. Throughout the 1980’s gastric
surgery became steadily less popular as an approach to the management of chronic relapsing duodenal
ulcer disease, even though fairly sophisticated techniques such as highly selective vagotomy had evolved
in an attempt to reduce gastric acid output with minimal side effects. Most series continued to show,
however, that surgery was associated with a 15-40% relapse rate, symptomatic and metabolic
complications were common, and concerns have been expressed about the long term cancer risks. The
safety and efficacy of medical maintenance treatment was a major factor in the rejection of gastric
surgery, and the advent of proton pump inhibitors in the late 1980’s, with their much more powerful
suppressive effect on gastric acid production, provided a means of healing most resistant ulcers. During
this period, aircrew with duodenal ulcer disease were routinely treated with H2 receptor antangonists,
subjected to endoscopic follow up and grounded for a lengthy period before being permitted to return to
flying duties. Relapsing ulcer disease was usually associated with maintenance therapy and a restricted
aircrew category.
Although the medical profession appeared slow to realise the significance of the discovery of spiral
organisms in the gastric mucosa of human beings with gastritis and ulcer disease, it is now widely
accepted that helicobacter pylori is an essential component in the aetiology of duodenal ulcer disease,
and is implicated in a high proportion of gastric ulcers. Eradication of the organism has been associated
with dramatic reductions in ulcer relapse rate in large numbers of series in the short term and evidence
for long term remission is also emerging. This has led to a radical re-think of the management of ulcer
disease in aircrew, with much shorter periods of grounding for uncomplicated ulcer disease, and
restoration of unrestricted flying category in those in whom ulcer healing and H pylori eradication is
confirmed. A more cautious approach is taken with complicated ulcer disease.
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Duodenal ulcer
Management Strategy in Military Aircrew
Uncomplicated DU - treat with ulcer healing agent and Helicobacter pylori eradication
- unfit all flying duties for 2/12
- endoscopy at 2/12, check ulcer healing and biopsy for H pylori
- or substitute breath test/faecal antigen test to confirm H pylori clearance?
- if clear, upgrade full flying duties
DU plus haemorrhage
- same treatment
- unfit full flying duties for 6/12
- check endoscopy and H pylori status
- if clear, return to full flying duties
Perforated DU
- downgraded 1 year
- H pylori eradication Rx if relevant
- check endoscopy at 1 year
- if clear, return to unrestricted flying duties
NSAID associated DU
- H pylori +ve: same as simple DU
- H pylori -ve: conventional Rx, check ulcer healing at 8/52, if
clear - full flying duties and no further NSAIDs
INFLAMMATORY BOWEL DISEASE
Ulcerative colitis and Crohn’s disease are the two most common forms in inflammatory bowel disease
and are chronic remitting/relapsing disorders requiring long term medical treatment and follow up. They
are prone to a spectrum of complications and their diagnosis has significant implications for the careers
of aviators.
Ulcerative Colitis
Ulcerative colitis is a chronic inflammatory disease of the large bowel, with a relapsing/remitting natural
history, and of unknown aetiology. The inflammatory process is normally confined to the mucosa,
starting in the rectum and spreading proximally to involve variably amounts of the colon. The aetiology
is not understood, but probably represents an interaction between genetic predisposing factors,
exogenous and endogenous triggers, producing an inflammatory process which is mediated by the
immune system.
Epidemiology
The disorder has a similar incidence throughout all ages after puberty, at around 5-8/100,000 in North
Western Europe and in people of Anglo-Saxon origin. It is notably less common in smokers.
Prognosis
©Prof. Anthony Batchelor
14
DAvMed 44
Haemo-endoc-gastro
KCL 2011
From the aeromedical view point it is more relevant to concentrate on the prognosis than to enter
lengthy discussion on the clinical features of the disorder which can be distilled from any standard text.
Ulcerative colitis is associated with only a slight excess mortality in the year of diagnosis and this is
almost entirely confined to pancolitis occurring in the elderly. There is no overall excess mortality. The
disorder is, however, a relapsing one and over 95% of patients can be expected to have relapsed by 10
years from the time of the presenting episode. Relapse rates appear to be directly related to the extent of
the colon involved, and are higher in the young. The most important observation, however, is that
relapses are totally unpredictable, which naturally has implications for aviators and also for military
personnel. One mode of therapy is surgical resection of the colon and 10-25% of subjects can expect to
have colonic resection by 10 years from presentation, depending upon their geographical location.
Surgical intervention tends to be offered at an earlier stage in Scandinavian countries than in the UK, and
some surveys have indicated that the social and employment consequences of the disorder are less
marked in these countries as well. The introduction of ileal pouch surgery has made colonic resection
appear rather more acceptable to patients, particularly to the young, but is not without its complications.
Not only is there a significant chance of relapse of disease activity, with over 30% of sufferers having a
relapse in any one year (45% in the 20-40 year age group), but there is also a significant risk of disease
extension with each relapse. In the longer term there is a well documented cancer risk associated with
ulcerative colitis, related to the extent of bowel involvement, the subjects age at presentation, and the
duration of disease. Cardiovascular mortality amongst sufferers, however, is reduced, and this is almost
certainly related to the lower cigarette smoking rate amongst subjects.
Management
The treatment of acute episodes will not be discussed, beyond saying that systemic and topical steroids
are the mainstay of therapy. Maintenance treatment, however, is a vital component of management and it
has been repeatedly shown that 5 aminosalicylic acid (5-ASA) delivered directly to the colon has a
significant positive impact on relapse rates, reducing the overall annual rate to around 10-15%. This
remains true even after lengthy periods of remission on treatment, so that discontinuing the drug is
associated with an immediate increase in annual relapse. The first 5 ASA drug was sulphasalazine in
which 5 ASA was bonded onto a sulphonomide antibiotic, thus avoiding absorption in the small intestine,
but the active agent being liberated by bacterial cleavage of the bond in the colon. A relatively high
incidence of side effects from this drug is related in large part to the sulphapyridine component and a
number of agents have now appeared on the market which use alternative approaches to targeted
delivery of 5-ASA in the colon. These have all been shown to be effective in reducing relapse rates, tend
to have a lower incidence of side effects, but their differing delivery patterns need to be considered when
targeting specific regions of the terminal ileum and colon. The one remaining concern is of
nephrotoxicity from 5-ASA which is exceedingly uncommon, but well recognised.
Factors Affecting Relapse Rates
Upper respiratory tract infections and analgesic ingestion have both been shown to have a significant
association with relapse of ulcerative colitis, but it is possible that they may represent the same
phenomenon, i.e. paracetamol/aspirin consumption for URTIs. Although it has been difficult to prove a
statistical association, many clinicians are convinced that gastroenteritis, dietary indiscretion, foreign
travel, and particularly physical and psychological stress, are also strongly related to relapse. A number
of these factors have significant implications for aircrew on world-wide operations, and military aircrew
in particular.
©Prof. Anthony Batchelor
15
DAvMed 44
Haemo-endoc-gastro
KCL 2011
Aeromedical Concerns
Sudden incapacitation is an unlikely event to be associated with ulcerative colitis when the disorder is in
remission. However, the disease has an unpredictable relapse pattern, and the need for medical
surveillance and for maintenance therapy, can be expected to have an impact on operational availability
of sufferers. Reduced operational efficiency may also be a factor worthy of consideration with many nonspecific symptoms having been clearly associated with ulcerative colitis, even in remission, and these
include a reduced sense of well being, fatigueability, and a variety of drug side effects. Irritable bowel
symptoms are also extremely common, even during remission, and the sense of rectal “unease” which
afflicts so many sufferers is undoubtedly a major distracting influence. For those aircrew with limited
disease in remission, return to restricted flying under regular supervision may be possible. For extensive
or complicated colitis, the outlook for a flying career is usually poor.
Crohn's Disease
Crohn’s disease is an inflammatory disease affecting the whole of the GI tract, usually distributed in a
patchy fashion and involving the large bowel only in 30%, the small intestine alone in 40% and both large
and small
intestines in 30%. The distal ileum is the commonest single site likely to be involved. Histologically it is
characterised by the presence of non-caseating granulomata, and involvement of the full thickness of the
bowel wall, in contrast to the predominantly mucosal disease of ulcerative colitis. The aetiology is
unknown, but unlike ulcerative colitis it is commoner in smokers and many patients appear to have had
diets containing an unduly high proportion of refined sugars early in life. It most commonly begins in
early adult life, follows a remitting relapsing pattern, and is frequently complicated by abscess and fistula
formation, haemorrhage, peri-anal disease, and obstructive symptoms.
Prognosis
The recurrence rate of Crohn’s disease is almost 100% at 10 years, and 30% of sufferers can expect to
have surgery performed in the first year, with a surgical intervention rate of 5% per year in the
remainder. In addition to local complications, nutritional deficiencies and anaemia are common, and
remote complications such as iritis and arthritis are not rare.
Aeromedical Disposition
Small bowel Crohn’s disease can rarely be expected to be compatible with a return to full flying duties
because of the unexpected relapses, complications and symptoms described above. Occasional
individuals in full remission, with no complications and maintained on low dose immunosuppressant
therapy (eg prednisolone, azathioprine) may be considered for restricted flying duties under close
supervision. If confined to the large bowel alone, limited and uncomplicated disease in complete
remission for one year, with resolution of endoscopic changes and no markers of disease activity, might
be compatible with a limited flying category for military aircrew, subject to six monthly reviews.
Generally the prognosis for a full flying career in this disease is exceedingly poor.
©Prof. Anthony Batchelor
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