A PHYTOTHERAPEUTIC PERSPECTIVE Clinical

Transcription

Clinical
Treating Autoimmune Disease
BY KERRY BONE
A PHYTOTHERAPEUTIC
PERSPECTIVE
PART 2
In the first issue of the Modern
Phytotherapist, a multifactorial model for the
development and treatment of autoimmune disease
was described. This model proposed two basic,
simultaneous requirements for the development of
autoimmune disease. These were the primary lesion,
which may be linked to an infection, and a state of
immune system dysregulation.
With this model, many event sequences are possible.
The simplest example is that the same microorganism acts as both the primary lesion and the
source of immune dysregulation. This may be the
case for the autoimmune destruction which can
occur with HIV-1 infection. In another example, a
person may be in a state of immune dysregulation
and then react inappropriately to an infection. The
infection passes, but the state of immune
dysregulation persists and, because of the influence
of the infection, develops into a self-sustaining
autoimmune process. In this instance, best results
will be achieved by concentrating treatment on the
immune dysregulation and the self-sustaining
inflammatory processes.
Another possible event sequence is that there is a
chronic presence of a micro-organism to which the
immune system is reacting in a normal way.
However due to molecular mimicry the microorganism is also capable of inducing a cross-reaction
with self tissue. But this cross-reaction only occurs
to a mild, non-damaging degree because the immune
system is behaving normally. This chronic presence
could also include a potentially pathogenic organism
in the bowel flora. Other events then create a state of
immune dysregulation and the immune system
begins to aggressively cross-react and destroy self
tissue. In this instance, both the primary lesion (the
micro-organism presence) and the cause of immune
dysregulation require equal attention.
Another variation is possible which could be relevant
to the development of multiple sclerosis. Here, at a
certain age, a viral infection creates a clone of
16 Modern Phytotherapist
lymphocytes which are capable of cross-reacting with
self tissue. However, because there is no immune
dysregulation, no damaging cross-reaction occurs
and these cells persist as memory cells after the virus
has gone. They are then reactivated by exposure to
the same virus, or one that is antigenically similar. If
this event coincides with a state of immune
dysregulation, autoimmune disease may develop. In
this example the best approach to treatment is to (i)
prevent the potential triggering effect of the second
viral exposure or infection and (ii) decrease the
immune dysregulation and self-sustaining
inflammatory processes.
The involvement of micro-organisms in the
development of autoimmune disease is a
controversial and confusing issue. Because an
autoimmune disease is not an infection, but rather
might be an abnormal response to micro-organisms
under particular circumstances, it would be
unreasonable to expect a single species of microorganism only to be implicated in each autoimmune
disease. This makes an “infectious” aetiology
difficult to prove, particularly if the implicated
micro-organisms vary from region to region and
from person to person. As might be expected from
the model, studies in the current scientific literature
have implicated the association of several microorganisms with each autoimmune disease. These
studies do provide useful information and will be
reviewed below.
Immune system dysregulation may be caused by
several factors acting together. For example the
adverse effects of infection, food intolerance and
stress may combine to create a state of immune
dysregulation. Each contributing factor should be
identified and addressed in the treatment protocol.
The type of micro-organism responsible and the
sequence of events leading to disease must be
determined for each patient. Often this
determination will not be possible, but a careful case
history and an up-to-date knowledge of the
particular disease label, eg “Crohn’s disease”, will
greatly assist this process.
For professional use only. Not for Public Distribution.
Clinical
A Simple Case History
Prescriptions were as follows:
A simple case history helps to illustrate the practical
application of the model. Post-streptococcal
glomerulonephritis may be caused by the deposition
of immune complexes in the glomerulus of the
kidney following infection with streptococci.
However autoimmune processes involving molecular
mimicry can also be involved.1 Usually the disease
occurs in children or adolescents, follows an acute
course, and resolves within weeks. However the
patient I treated had his first episode of proteinuria
at 18, and then regularly had attacks ever since. Each
attack was characterised by malaise and proteinuria
and had been treated with high doses of
corticosteroids, but not antibiotics. So presumably
for this patient, the disorder was regarded as
autoimmune, albeit probably with an infectious
origin. He sought herbal treatment because the
frequency of attacks had recently increased in
association with greater stress at work.
General Formula
The case history revealed that attacks occurred
during times of stress or being “run down” and could
be preceded by a sore throat or upper respiratory
viral infection. I concluded that a viral throat
infection followed by a streptococcal secondary
infection acted as the primary lesion. The immune
dysregulation was probably caused by stress and the
viral infection. The treatment approach was as
follows:
Dose: 2 mL in 15 mL taken as a deep gargle twice
a day. The gargle is swallowed after use.
1
A general immune-enhancing, tonic and antiinflammatory formula to prevent infections and
decrease resultant immune dysregulation.
2
Regular use of a herbal gargle. The gargle had
immune-enhancing and antiseptic properties to
prevent viral or bacterial overpopulation of the
mucous membranes of the throat.
3
Containment of upper respiratory infections.
This particular treatment was to be used during
infections instead of that described in 1) above.
Echinacea (Echinacea angustifolia)
1:2
35 mL
Picrorrhiza (Picrorrhiza kurroa)
1:2
15 mL
Astragalus (Astragalus
membranaceus)
1:2
25 mL
Rehmannia (Rehmannia glutinosa)
1:2
25 mL
100 mL
Dose: 7.5 mL with water twice a day.
Herbal Gargle
1:2
40 mL
Propolis
1:10
60 mL
100 mL
Infection Formula
1:2
40 mL
Licorice (Glycyrrhiza glabra)
1:1
15 mL
Ginger (Zingiber officinale)
1:2
5 mL
Yarrow (Achillea millefolium)
1:2
40 mL
100 mL
Dose: 5 mL with warm water 5 to 6 times a day
during infection. Commence treatment at the first
sign of infection and stop taking general formula.
Resume general formula when over infection.
Initially, another attack occurred about one month
after treatment began. In the 3 years since, only one
attack has occurred after the patient was up late and
drank heavily while under considerable stress. The
reduced frequency of attacks can be attributed to the
herbal treatment, since the patient currently
experiences just as much stress at work as at the time
of the first consultation.
Modern Phytotherapist 17
Clinical
Ankylosing Spondylitis
Good Evidence to Implicate
Molecular Mimicry
As described in Part 1 of this article, there is good
evidence to implicate molecular mimicry in the
cause of ankylosing spondylitis (AS). This has direct
implications for its treatment. After reviewing the
factors implicated in AS, I will then explore its
treatment in greater detail.
•
Ankylosing spondylitis is often grouped with reactive
arthritis. Both diseases occur predominantly in
individuals who are positive for the HLA-B27 tissue
marker. For cases of reactive arthritis and Reiter’s
syndrome, a clear association with an infecting
organism such as Salmonella, Shigella, Chlamydia,
Yersinia or Campylobacter is observed.
Reactive arthritis can follow urogenital or intestinal
infection with these bacteria. In the case of AS there
is no clear proof of infection, and considerable
controversy still surrounds the concept of an
infectious aetiology. AS almost always follows a
chronic course, whereas only 10% of patients with
reactive arthritis have evidence of active disease 20
years after the onset. However, evidence is growing
that AS is triggered by the asymptomatic presence of
pathogenic bacteria, particularly in the intestine.
The bacteria may not occur in sufficient numbers to
cause a frank infection, but this fact may also help to
sustain their persistence in the body, a persistence
which can lead to a chronic course of disease.
•
•
The following evidence exists for a bacterial
trigger for AS:
•
•
Considerable evidence exists that bacteria such as
Klebsiella, Enterobacter, Salmonella, Shigella and
Yersinia immunologically cross-react with HLAB27.2 (It is doubtful whether severe disease
occurs in the small number of AS patients who
are HLA-B27 negative.)2
More than 50% of AS patients with peripheral
arthritis have inflammatory gut lesions.3 The
degree of gastrointestinal inflammation was
significantly correlated with the degree of joint
inflammation in 45 patients with AS.4 The
chronic gut lesions resemble inflammatory bowel
disease.3 Recently it was demonstrated that the
intestinal secretory immune system was
significantly overstimulated in active AS, and this
was reflected by raised serum levels of IgA.5
•
When the gastrointestinal anti-inflammatory
drug sulphasalazine was given, there was
normalisation of immune activity in those
patients who responded clinically. Another study
found that chronic lesions of the gut were
frequently found in patients with AS.6
Of the above micro-organisms, Dr Alan Ebringer
found that only Klebsiella could be consistently
isolated from faecal cultures obtained from
British patients with AS.2 In a study of 63 AS
patients by Ebringer’s group, an increased
recovery of Klebsiella could be obtained during
the clinically active phases of the disease.7 A
second study showed that a positive culture of
Klebsiella in patients with inactive disease was
subsequently followed by a relapse.8 The same
research team found that the presence of
Klebsiella was strongly associated with episodes
of anterior uveitis in AS patients.9 Some
scientists in other countries have confirmed this
association with Klebsiella, but several other
research groups have not. It is possible that other
organisms might be associated with AS in other
countries (see below).
Another group of scientists found that a
substantial portion of patients with AS have
antibodies which react to both HLA-B27 and
Klebsiella pneumoniae nitrogenase.10 Amino acid
sequence similarities (ie molecular mimicry) had
previously been demonstrated between Klebsiella
nitrogenase and HLA-B27 (see part 1 of this
article). However molecular mimicry between
the two proteins was not confirmed by a research
team from Finland.11
Since 1980, the British group led by Ebringer has
concentrated on finding antibodies to Klebsiella
in the bloodstream of patients with active AS.
This association has been confirmed in several
controlled studies using several different
techniques to measure anti-Klebsiella antibodies.2
However, in a New Zealand study, antibodies to
Yersinia were also associated with AS in 4 out of
15 cases.12 Twenty-nine control subjects had no
serum antibodies to Yersinia.
Recently, research on the association between
reactive arthritis, AS, HLA-B27 and infection has
taken a different course. Previous studies have
concentrated on serum antibodies and their
cross-reactivity. Antibodies are the products of B
lymphocytes. However HLA-B27 is a Class 1
HLA antigen which is thought to govern the
reactivity of CD8+ cells (cytotoxic T
lymphocytes).
Clinical
If the disease association is a consequence of
antigen presentation, the disease should be
mediated by CD8+ cells, in a T lymphocyte
version of molecular mimicry.
In what has been described as “the missing link”
in the cause of the HLA-B27-associated
arthropathies, B27-restricted CD8+ cells, which
showed specificity for both autoantigens and
arthritogenic bacteria such as Yersinia, have been
isolated from the synovial fluids of patients with
reactive arthritis and AS.13
•
Non-secretors of ABO blood group antigens are
more susceptible to infection. The fact that nonsecretors of ABO are 2.6 times more likely to
have AS supports an infectious aetiology for AS.14
• The site of the bacterial trigger for AS is not
necessarily always the bowel. An association
between AS and chronic bacterial prostatitis has
long been observed. The incidence of chronic
prostatitis in male AS patients was 83%,
compared to 33% in patients with rheumatoid
arthritis.15 This association was confirmed in a
later study.16 The fact that the prostate may
harbour a bacteria which contributes to AS could
explain the higher incidence of this disorder
in males.
Consideration of the above and other similar
findings led Dr John Vaughan to conclude in a recent
review: “The probability that AS is due to a peculiar
immunologic relationship between the patient and
his enteric organisms, and that this is determined by
his HLA-B27 molecules, seems great.”17
The information on possible sources of immune
dysregulation in AS is less clear. However, enhanced
gastrointestinal permeability, the so-called leaky gut,
could be such a source. Normally, small amounts of
lipopolysaccharides (endotoxin) enter portal venous
blood and are eliminated by phagocytic cells in the
liver.18 Increased mucosal permeability may result in
the increased exposure of the body to such proinflammatory bacterial fragments.
Studies have demonstrated an increased intestinal
permeability in AS.19 - 21 These findings also support
the notion that asymptomatic gut inflammation,
possibly due to pathogenic bacteria, is a factor in the
pathogenesis of AS.
Other factors which have been associated with AS
and may reflect on immune dysregulation include
trauma22 and delayed hypersensitivity.23 Reactive
arthritis and Reiter’s syndrome have been reported
after hepatitis B vaccination24,25 and this could also be
a factor in some cases of AS.
Treatment Approach
From the above, a key part of the treatment
approach to AS is to reduce the presence of Klebsiella
or other potentially pathogenic organisms.
This will not only reduce the stimulus for immune
cross-reactivity, but will also decrease
gastrointestinal inflammation and the resultant
increased permeability.
Klebsiella in the bowel uses starch as a major source
of nutrition, so a low starch diet should decrease its
numbers. Ebringer recommends that patients with
AS should avoid bread, pasta, cereals of all sorts, rice,
potatoes and sugary foods. They can eat unrestricted
amounts of vegetables (excluding starchy root
vegetables such as potatoes and yams), fruit, eggs,
cheese, fish and meat.26 Legumes such as soya beans
and uncooked bananas contain a significant
proportion of indigestible starch which may act
as a food source for Klebsiella. They should also
be avoided.
Ebringer claims that the majority of 200 patients on
this diet have had their disease process halted.
However a significant result may take 6 months or
more.26 To date, these results have not been
published in a scientific journal, possibly because of
their controversial nature. Patients with AS could
also be placed on the Bowel Flora Regime (see
Inflammatory Bowel Disease later in this article).
Herbal treatment for AS should be selected
from the following:
•
•
•
•
Immune-enhancing herbs such as Echinacea,
Picrorrhiza and Astragalus to eliminate
pathogenic organisms.
Gastrointestinal antiseptics such as Berberis
(Barberry), Hydrastis (Golden Seal), Allium
sativum (Garlic) and Propolis to eliminate
pathogenic organisms from the bowel.
Gastrointestinal healing and anti-inflammatory
agents such as Calendula, Filipendula
(Meadowsweet), Matricaria (Chamomile) and
Propolis to reduce inflammation and
heal the gut wall.
Echinacea and Silybum (St Mary’s Thistle) to
reduce the systemic impact of a leaky gut wall.
Clinical
•
•
•
Suitable treatment for the prostate if
chronic prostatitis is present, using herbs
such as Pygeum.
Anti-inflammatory herbs such as Salix (Willow
Bark), Glycyrrhiza (Licorice) and Bupleurum to
help control symptoms and break the vicious
cycle sustaining the tissue destruction.
Tylophora or Stephania may be useful to control
cross-reacting CD8+ cells.
Myasthenia Gravis
Myasthenia gravis (MG) is an organ-specific
autoimmune disease caused by an antibodymediated assault on the muscle acetylcholine
receptor (AChR) at the neuromuscular junction.
Binding of antibodies to the AChR leads to loss of
functional AChR’s and impairs the neuromuscular
signal transmission, resulting in muscular weakness.
About 90% of patients have thymic abnormalities
and 10% have thymoma.
In contrast to AS, and despite the fact that MG is a
well-defined autoimmune disease, there is only weak
circumstantial evidence associating infectious agents
with the onset of MG. MG associated with thymoma
is probably an indirect result of the tumour, although
a virus may be involved (see below).27 In patients
who do not have thymoma, it has been postulated
that MG may be traced to an exposure to microorganisms carrying molecules that, with respect to
immune surveillance, mimic AChR.27
Molecular mimicry has been demonstrated between
AChR and viruses and bacteria. Notably, crossreactivities have been demonstrated between AChR
and proteins from herpes simplex virus,28
poliovirus,29 Eschericia coli, Klebsiella, Yersinia and
Proteus vulgaris.30 Sera from patients with MG were
shown to contain antibodies which reacted strongly
to two proteins from Yersinia.31 However, it was not
shown that these antibodies also bound to AChR.
Antibodies against a certain type of dextran, derived
from the cell walls of bacteria found in bowel flora,
can create further antibodies which cross-react with
AChR.32 It was then shown that 12 of 60 MG
patients had antibodies against this dextran, whereas
none of the 40 controls did. However, it has not
been proven that these antibodies against dextran
then lead to the production of anti-AChR antibodies.
However, earlier studies failed to isolate a virus from
the thymuses of patients with MG.34 MG occurred in
five individuals within a few weeks of rabies virus
vaccination.35 The rabies virus binds to AChR, and
thus a consequence of the anti-viral response is that
some antibodies will be against AChR and invoke, in
this instance, a transient case of MG.
The scientific studies provide few leads for the herbal
treatment of MG in accordance with the model
described in Part 1 of this article. However, attention
to the possible presence of naked and enveloped
viruses, and to the normalisation of bowel flora (eg
see Bowel Flora Regime below), may yield results.
The successful application of the treatment model is
described in the following case histories.
Case Histories
(Provided By Nicholas Burgess)
Case History 1
A 30 year old woman presented with MG, which was
mainly ocular, but had been manifesting in her arms
for the last 3 months.
She took the drug pyridostigmine bromide, 120 mg
per day and was also taking a multi-vitamin,
potassium and vitamin C, 1,000 mg x 2 daily.
Onset was six months prior to her first visit. It
started with a drooping eyelid and then double
vision. Specialist stated thymus was normal, so
thymectomy unnecessary. Patient also experienced
severe dysmenorrhoea and had occasionally lost
consciousness from the pain. Has had ovarian cysts
removed. Also suffers severe migraines, but not since
taking pyridostigmine bromide.
Prior to initial onset of the MG, patient had
experienced severe gastroenteritis and had taken over
one month to recover. She then had a severe bout of
‘flu. Patient had very low energy and often felt
lethargic, especially since the gastroenteritis. She also
has a lot of flatulence.
Spends a lot of time worrying about the disease,
although not really depressed. Sleeps well, but has an
atrocious diet, high in dairy, refined carbohydrates
and chocolate.
Epstein-Barr virus DNA was found in six of eight
thymuses of patients with thymoma or thymic
hyperplasia.33 Four of the six patients had MG.
Clinical
Treatment Outline
Dietary changes were a main priority, especially the
elimination of dairy and excessive reliance on
convenience foods and refined carbohydrates.
Patient told to eat much more fruit and vegetables. I
decided it was necessary to use gastrointestinal tonics
and liver tonics to improve the patient’s digestive
function, tone the gut wall and improve liver
screening of ingested toxins. This, together with
the dietary changes, would help to improve her
bowel flora.
At the second consultation two weeks later, the
patient felt much the same. Symptoms, if anything,
had possibly worsened and she was extremely upset
following speaking to her neurologist who told her
that the disease was progressive and that she was
bound to feel worse as time went by. I decided to
change my approach in a few ways. Holistically, I
realised that she was very nervous and had been
under so much stress that she needed an adrenal
tonic and relaxant. I also decided to use a different
approach as regards the immune system and the gut,
so I prescribed:
For the Gut
Wormwood (Artemisia absinthium)
1:5
10 mL
Golden Seal (Hydrastis canadensis)
1:3
40 mL
50 mL
Dose: 15 drops with water before meals.
For the immune system etc
1:2
15 mL
Cramp Bark (Viburnum opulus)
1:2
10 mL
1:2
25 mL
Withania (Withania somnifera)
1:2
30 mL
Hemidesmus (Hemidesmus indica)
1:2
20 mL
100 mL
Dose: 5 mL with water t.d.s.
Again the aim of the treatment was to improve
digestion and bowel flora. The Rehmannia was the
adrenal tonic, Withania was included as a tonic and
Viburnum opulus as a relaxant. Picrorrhiza was given
as an immune enhancer to help her body eliminate
pathogenic viruses or bacteria. Hemidesmus was to
break the vicious autoimmune cycle.
On the changed mixture, she rang in two weeks to
say that she was feeling quite a bit better and that she
thought the mixture was helping. There were still
mild problems with the arms, but not nearly as bad.
Out of ten days, she had six days with no symptoms,
two days with mild symptoms and two days where
symptoms were bad. So I re-prescribed the same
formula for a month.
After one month, she was feeling well and had been
totally symptom-free for over ten days. Prior to that,
she had only the occasional bad day and nothing
really bad for a month. She had cut back her dose
of pyridostigmine bromide to 40 mg in the morning
and then two doses of 30 mg. Her main problems
were in the morning. Energy levels had definitely
improved. Since she complained about taste, I
changed the mixture slightly at this point by adding
5 mL of Flavouring Mixture per 100 mL of above
formula. I repeated the digestive formula unchanged.
I said to her that I would like her to continue
on this regime now for two months before
another consultation.
After one month the patient was having tests with a
gynaecologist and was told not to take the
pyridostigmine bromide for a few days before the
tests. She discovered that she felt really well without
the pyridostigmine bromide. One month later, (this
is now four months after initial consultation) the
patient underwent three hours of testing by her
neurologist and was told the disease has gone into
complete remission except for very slight ocular
weakness. She now had no period pain, and
although she had experienced migraines, was doing
extremely well.
Changed formulas for before and after meals by
adding Tanacetum parthenium (Feverfew) to the
digestive drops and Zingiber (Ginger) to
the main formula.
Two months later, another appointment with specialist
who said that she is the healthiest myasthenia patient
he has ever seen. She was told to stop taking the
pyridostigmine bromide and just use it if she needs it,
“like an aspirin”. Same treatment continued.
Patient rang the day I wrote this account to say she
has not had a single symptom or any pyridostigmine
bromide for two full months. The case continues.
Clinical
Case History 2
Patient, 29 years, woman, with quite bad MG.
Difficulties with speech, swallowing, weight loss,
drooping eyelids, weakness in arms, tiredness, and
difficulty chewing. Diagnosed 18 months before first
coming to see me. Disease is much worse in the
early mornings.
Taking 60 mg pyridostigmine bromide every three
hours and specialist had recommended a thymectomy.
Case history includes tonsillectomy and gastric ulcer
(stress related). She had taken antacid preparations
(aluminium hydroxide, magnesium hydroxide,
magnesium trisilicate, simethicone) constantly
between the ages of 16 and 25.
Has a difficult job, which involves considerable
physical and mental work. Has difficulty sleeping,
diet poor, based on convenience foods, refined
carbohydrates, drinking lots of tea and coffee. Very
little in the way of fruit and vegetables or fresh food.
Has a very poor appetite and has virtually constant
diarrhoea. She also has a lot of flatulence. Has had
cystitis on and off for two years before the diagnosis,
she has psoriasis on elbows and her scalp. She gets
severe premenstrual tension and period pain, and has
been taking the birth control pill for the last two
years. Constitutionally a very cold person, she gets
headaches once a week, at least.
Treatment outline:
1
Holistic Considerations - Work on the diet first,
high amounts of fruits and vegetables, complex
carbohydrates and good quality proteins. The
virtually-constant diarrhoea implied that
working on the gut flora, including using
slippery elm and Hydrastis, was a high priority.
Digestive stimulants before meals were needed.
She was a very nervous and anxious person and
needed some kind of nerve tonic and
even an antidepressant.
2
Symptoms - Takes pyridostigmine bromide,
so I decided to deal with the perceived
underlying causes.
3
Perceived Cause - I decided to use
immunostimulants and antivirals, especially
focusing on the gut.
I prescibed the following:
Herbal Fourmula
Gentian (Gentiana lutea)
1:5
30 mL
Ginger (Zingiber officinale)
1:2
20 mL
50 mL
Dose: 20 drops with water before each meal.
Herbal Formula
St John’s Wort (Hypericum
perforatum)
1:2
30 mL
1:3
10 mL
1:2
20 mL
1:2
10 mL
1:1
20 mL
Prickly Ash (Zanthoxylum
clava-herculis)
1:2
10 mL
100 mL
Dose: 5 mL with water after meals t.d.s.
In the above formulas, the Hypericum acted as an
antiviral and antidepressant and nervine tonic.
Picrorrhiza and Echinacea were to boost immune
function to resolve the influence of pathogenic
organisms. Hydrastis was for the gut and flora,
Glycyrrhiza was anti-inflammatory and tonic, and
Zanthoxylum was a circulatory stimulant. The
Gentiana and Zingiber were digestive stimulants, and
Zanthoxylum and Zingiber were particularly
indicated for her cold constitution.
She rang ten days later and reported that she had a
severe flu. So I gave her a diaphoretic tea and some
more Echinacea to take separately. She recovered
quite well. I also repeated the same mixtures and
arranged to see her in a further two weeks.
At the next appointment, she had been feeling quite
a lot better, and had seen the specialist who said that
the myasthenia was mild and that there would be no
need for a thymectomy. She was not feeling nearly as
tired. Bowels were still quite loose and she was
continuing her stressful occupation as normal.
Clinical
Diet still had very little protein. Recommended
taking some good quality protein foods (she was
quite a thin woman). Continued on similar
treatment for one month.
with diarrhoea and abdominal cramping, so I felt
that we should try something different. With a view
to resolving the Helicobacter I changed the
treatments to:
At third consultation, there had been a major
improvement. Feeling a lot better. Improved speech
and swallowing. Still some difficulty with chewing
and the drooping eyelids. Sleeping well and
diarrhoea improved. Also, patient now taking
pyridostigmine bromide only three times per day.
No problems with focusing.
The next week, the patient rang to say that she was
experiencing “a lot of activity in her gut” and I said
this was to be expected. She seemed to be doing well
with regard to the myasthenia. I recommended that
she continue.
One month later, has had holidays and has been
feeling great. This was except for one weekend prior
to appointment, where she had diarrhoea again from
having lunch in a restaurant with friends and not
being careful of her diet.
Finally recommended giving up dairy products,
going on a strict dairy-free diet. From this point on,
she improved markedly. The dairy was probably
providing a potent source of immune dysregulation.
She had taken up meditation daily. The diarrhoea
and looseness of the bowels had gone completely
since she gave up the dairy products.
Two months later patient doing extremely well,
except diagnosed with Helicobacter pylori. Protracted
discussion followed, about the pros and cons of the
medically suggested antibiotic regime. Previously the
patient had reacted extremely badly to antibiotics,
Herbal Formula
1:2
45 mL
Propolis
1:10
50 mL
Wormwood (Artemisia absinthium)
1:5
5 mL
100 mL
Dose: 2 mL with water before each meal.
Herbal Formula
Calendula (Calendula officinalis)
1:2
20 mL
1:2
30 mL
Withania (Withania somnifera)
1:2
30 mL
1:2
10 mL
1:1
10 mL
100 mL
Patient continued on this regime, was doing quite
well and was down to taking pyridostigmine bromide
twice a day, but continued the high-stress lifestyle,
and refused to change.
Inflammatory Bowel Disease
Ulcerative colitis and Crohn’s disease represent a
group of chronic inflammatory disorders of the
bowel of unknown origin. The incidence of
ulcerative colitis (UC) is relatively stable, while
Crohn’s disease (CD) continues to rise in frequency
as industrialisation increases worldwide.36,37 UC and
CD share many features, but they are independent
and perhaps distantly related diseases.
Although evidence supports a genetic predisposition
to both UC and CD, for example first degree relatives
of patients have a 10-fold increased risk of
developing the same disease,38 environmental factors
probably predominate, especially for UC. The
probability of an identical twin having the same
disease is only 6.3% for UC, but it is 58% for CD.39
However, the above association for CD observed for
twins might still reflect on environmental factors. A
recent study described the clustering of CD in two
French families living in nearby towns.40 In the first
family, all members developed CD. One of the sons
who developed CD in 1974 met a girl whom he
subsequently married in 1983. She developed CD in
1991. In the second family, 7 of the 11 children
developed CD. Extensive testing for pathogens did
reveal one possible association. Antibodies to Breda
virus were detected in 6 of 10 affected family
members and 2 of 5 unaffected family members.
Moreover, for both families, there seemed to be a
distinct periodicity in disease emergence: 7 cases
from 1970 to 1974 and 4 cases from 1982 to 1984.
The authors concluded that the findings were
suggestive of a causative infectious micro-organism
with a considerable latency interval between
exposure and the emergence of clinical disease.
Clinical
Epidemiological studies have provided other
interesting associations. Smoking protects against
UC, but is a risk factor for CD, as is passive smoking
in the infant.41,42 Smoking also hastens the recurrence
of CD after remission.43 Use of oral contraceptives
was associated with an increased risk for both CD
and UC, as was lack of regular physical activity.44 A
Swedish study of CD and UC found that the risk of
CD was increased by a high sugar intake, and
decreased by a high fibre intake.45 These findings
support those from earlier studies.46 The most
striking finding of the above Swedish study was the
large increase in risk for both UC and CD (about 4
times) from eating fast foods at least twice a week.
CD has also been associated with the consumption of
recycled cooking oil. 47
A number of epidemiological studies have revealed
associations which may reflect on bowel flora and
disturbed immunological function. Sufferers of CD
were more likely to have experienced during
childhood an increased frequency of infections,
otitis, pharyngitis, tonsillectomy and antibiotic
treatment for these.48 In contrast, patients with UC
were only linked to an increase in childhood
infections. Urban living during childhood increased
the risk for CD only.48 Patients with CD are slightly
more likely to have had their appendix removed, but
those with UC were considerably less likely to have
had an appendectomy.49 Lack of exposure to enteric
infections in childhood may predispose to UC.50
However the fact that appendicitis has been linked to
delayed enteric infection argues against this
association.51 Moreover, a recent study found that
CD, but not UC, was significantly more common in
subjects whose first houses had running hot water
and a separate bathroom - indicators of increased
hygiene and hence reduced exposure to childhood
enteric infections.52 The link between CD and
domestic hygiene may explain the increasing
incidence of CD.
Strong evidence now exists to support the hypothesis
of a microbial trigger for CD. Although the
association of bacteria, viruses and bowel flora with
CD may confound a clear infectious cause, such a
multiplicity of factors is consistent with our
proposed model for the development of
autoimmune disease. In the case of CD, a virus
probably provides the primary lesion. This is
possibly followed by a long latency period until a
combination of effects from bacteria, imbalanced
bowel flora, diet and stress trigger a state of immune
dysregulation which results in active disease. A
similar theory for the cause of CD has been recently
proposed by French scientists.52
Viruses
In 1991, at the Third Oceania Symposium on
Complementary Medicine, I reviewed the known
factors involved in the aetiology of CD. At the time,
I could state that there had been no clear association
of viruses with the onset of CD. Since then, the
situation has changed dramatically.
Early research failed to find convincing evidence for
viruses. Intestinal tissue filtrates from patients with
CD frequently produced a cytopathic effect, and the
presence of small RNA viruses was implicated.53,54
However, the transfer of tissue from patients with
CD failed to reproduce the disease.55 Later it was
shown that a cytopathic effect could also be
produced by normal bowel tissue.56 No evidence for
persistent viral infection was found in CD tissue
using several different techniques.57 This
inconclusive situation remained for over a decade
until a team of British scientists re-examined the
association of viruses with CD.
A group led by Dr Andrew Wakefield at the Royal
Free Hospital in London completed a study of CD
tissue specimens. Based on this study they proposed
that the primary lesion in CD was a vasculitis caused
by multifocal intestinal infarction.58 They further
proposed that this injury was consistent with a cellmediated response to a persistent viral infection of
mesenteric microvascular endothelium. Of the
viruses known to infect vascular endothelium, the
measles virus was of particular interest for two
reasons: it localizes to the intestine and it can persist
for many years. They began to search for the measles
virus. Intestinal tissue from 10 patients with CD
were all found to contain measles virus RNA.59
Moreover measles virus RNA was found within
vascular endothelial cells associated with
inflammatory foci in 9 out of the 10 CD patients.
Other tests also supported the presence
of measles virus.59
A Swedish epidemiological study subsequently found
that children born during the 3-month period
following a measles epidemic were significantly more
likely to develop CD in later life.60 However no
association with measles was observed for UC.60
Wakefield is of the opinion that measles vaccination
may be responsible for the rise of CD cases in
Clinical
children. This rise is 7-fold in Scotland over the last
20 years, whereas cases of measles infections there
have dropped dramatically. However, vaccination
may not be the only explanation for this rise.
Moreover, fewer cases of measles infection might not
necessarily reflect that general exposure to the virus
is less.
Mycobacteria
Considerable research attention has been given to the
possible association of mycobacteria with CD. The
original account by Crohn described a disease that
closely resembled intestinal tuberculosis. Johne’s
disease, which occurs in cattle and other ruminants,
is very similar to Crohn’s disease and is caused by
Mycobacterium paratuberculosis. In 1984 Chiodini
and co-workers reported the isolation of a strain
resembling M. paratuberculosis from the intestinal
tissue of 3 patients with CD.61 This report initiated
both interest and controversy about a mycobacterial
aetiology for CD. One problem is that, on culture,
mycobacteria isolated from CD tissue initially appear
as cell wall-deficient forms that are difficult to
identify by conventional techniques.62 With the
development of the enzyme PCR (polymerase chain
reaction), which replicates DNA, DNA from M.
paratuberculosis has been detected in cultures from
CD patients.62 M. avium has also been identified in
the intestinal tissue of patients with CD.63
Many other groups of investigators have isolated
mycobacteria from CD patients,64,65 although not all
patients and not all studies have yielded positive
results.63 - 67 In a study reported by Sanderson and coworkers, M. paratuberculosis DNA was identified in
gut wall tissues from 65% of CD patients, 4.3% of
patients with UC and 12.5% of control patients.68
Other researchers found raised antibodies specific to
M. paratuberculosis in 84% of patients with CD.69
Such findings led a scientist working in the field to
conclude that the evidence for a mycobacterial
association with CD is “stronger now than it has
been before”.65
One problem which has led to scepticism about the
above statement is that there is inconclusive evidence
that CD results from an actual mycobacterial
infection. Only the presence of mycobacteria has
been proven. PCR technology can detect very small
amounts of bacterial DNA, as low as several hundred
bacteria per g of tissue. From an immunological
point of view, it is difficult to see how so few
organisms alone could elicit such a strong
inflammatory response, especially since the form of
M. paratuberculosis implicated in CD may
lack a cell wall.70
However, in accordance with the model proposed in
Part 1 of this article, mycobacteria are possibly acting
as a source of immune dysregulation, and the main
inflammatory stimulus is elsewhere, for example the
measles virus. Therefore the presence of
mycobacteria is still a significant finding, despite
their low numbers.
Another problem with the mycobacterial theory is
that antimycobacterial chemotherapy has yielded
inconclusive results.71,72 However, slowly growing
bacteria such as mycobacteria require long periods of
treatment, and mycobacteria also exhibit bacterial
persistence. This means that antibiotic therapy is
unlikely to be successful in eliminating the
pernicious influence of mycobacteria in CD. A
superior approach is to:
•
•
promote their killing by enhancing
immune mechanisms
encourage healthy bowel flora which may crowd
out or destroy pathogenic bacteria
Other Bacteria
Other bacteria have been implicated in CD, but
results are often conflicting. For example, one study
found that 93% of patients with CD had antibodies
against Chlamydia, compared to 26% in the control
group.73 However, another study failed to find
evidence of Chlamydia infection in CD patients.74
This discrepancy could be due to the testing of
different patient populations. That is, depending on
environmental circumstances, Chlamydia may act as
a pathogenic factor in CD. Antibodies to Klebsiella
were also higher in a population of CD patients.75
Coryneform bacteria were found in lymph nodes of
27 of 76 patients with CD, but only 3 of 41 controls.76
Such organisms may take on a cell wall-deficient
form in lymph nodes or other tissue. Bacterial
variants, that is, cell wall-deficient forms of bacteria
have been isolated from CD tissues in several
studies.77, 78 These organisms were Pseudomonas-like.
Mollicute-like organisms (MLO) are cell walldeficient intracellular bacterial pathogens. They
cannot be cultured by microbiological techniques
Clinical
and can only be detected in cells with an electron
microscope. Recently, MLO were found in the white
blood cells of patients with CD.79 Given the stronger
evidence for the association of measles virus and
mycobacteria with CD, the above research may not
carry much significance. However, it does illustrate
the potentially elusive nature of putative pathogens
in autoimmune disease.
Bowel Flora
There is little doubt that the faecal stream plays an
important part in the progression of CD.80 - 82 Bowel
flora are likely to be a strong source of immune
dysregulation in CD. Monocytes from CD patients
showed enhanced stimulation by bacterial cell wall
products such as lipopolysaccharide.83 Bacterial wall
fragments in the bowel wall of CD patients caused
enhanced immune responsiveness of monocytes.84
When 36 tissues from 16 patients with CD were
examined, no evidence of the presence of many
pathogenic bacteria and viruses were found.85
However, E. coli and streptococcal antigens were
found in 69% and 63% of the 16 cases studied,
respectively. Both E. Coli and streptococci are
normal inhabitants of bowel flora. The above results
suggest that some of the granulomas in CD may
result from the immunological processing of bowel
flora antigens following their penetration through a
compromised mucosa.85 Serum antibodies to bowel
flora bacteria are increased in CD patients.86
Pathogenic forms of E. coli adhere to the gut mucosa.
E. coli isolated from patients with UC and CD
showed a significantly greater index of adhesion
when compared to normal controls.87
Bowel Permeability
A leaky gut would enable enteric antigens to
penetrate the mucosa to an increased extent, and the
capacity for removal or degradation of this antigenic
load could then be exceeded. This would create a
state of immune dysregulation. Several studies
indicate permeability abnormalities for both the
small and large intestine in CD.88 In fact, so
characteristic is this enhanced permeability that it is
considered a good marker of active inflammation
occurring in CD patients in remission.89 Circulating
levels of lipopolysaccharide are increased in patients
with active CD.90 There is a general leakiness of the
intestinal mucosa in CD which is not dependent on
the presence of inflammatory lesions.88 It has been
postulated that increased permeability may be a
primary expression of CD and an important
pathological factor.88
In support of the concept that increased permeability
is a pathogenic factor, CD has been associated with
the use of nonsteroidal anti-inflammatory drugs
(NSAID). These drugs are responsible for increased
gut permeability and small intestinal inflammation.91,92 A group of researchers from Jersey
recently reported that of 60 new cases of colitis, 23
had developed while the patient was taking NSAID.93
None of these 23 patients had a known pre-existing
IBD. Diclofenac and mefenamic acid were the most
frequently observed associations. On endoscopic
examination, some cases were indistinguishable
from UC.
Diet
Food is a potential source of many immuneprovoking antigens, and food is probably therefore a
potent source of immune dysregulation in CD. It is
a well-accepted observation that many patients with
CD improve substantially when they are placed on
an elemental diet, that is, a predigested liquid diet
free of antigenic challenge consisting of amino acids,
dextrin, vitamins, vegetable oil, minerals and so on.94
An elemental diet also decreases small intestinal
permeability in CD.95
The concept of using an exclusion diet to treat CD
was first proposed by a group at Cambridge,96 and all
subsequent publications have originated from
England. The Cambridge group found that during a
controlled trial of 20 patients with CD, 7 of 10
patients on an exclusion diet remained in remission
for 6 months, compared to none of the 10 on a
normal fibre-rich diet.96 In an uncontrolled study, an
exclusion diet allowed 51 of 77 patients to remain
well on diet alone for periods up to 51 months, with
an average annual relapse rate of less than 10%.96 In
both trials, remission was first induced using an
elemental diet or total parenteral nutrition. Patients
were introduced a single food each day, starting with
those such as chicken and fish which, from
experience, are unlikely to provoke symptoms,
leaving until later cereals and dairy products which
are much more likely to cause symptoms. Foods
most likely to cause symptoms were, in descending
order, wheat, dairy products, brassicas, corn, yeast,
tomatoes, citrus, eggs, tap water, coffee, bananas,
potatoes, lamb and pork.96
Clinical
These results were confirmed in a recent large-scale
controlled trial on 78 patients.97 Corticosteroid
therapy was compared to an exclusion diet. Patients
on the exclusion diet also received placebo. Results
for diet treatment were favourable, median remission
periods were 3.8 months in the corticosteroid group
and 7.5 months in the group treated by diet.
Intolerances discovered were predominantly to
cereals, dairy products and yeast. The authors
concluded that diet provides a further therapeutic
strategy in active CD.97
This conclusion has been challenged by a
contemporary study.98 While this study did identify
food intolerances in CD patients, and several of these
were confirmed by a double blind challenge, there
was no significant difference in the duration of
remission between patients who did or did not
identify food sensitivities.98 The authors concluded
that food sensitivities in CD are variable, often do
not persist and are not of sufficient importance to
justify exclusion diets. However, it can be argued
that CD patients who are not food sensitive are not a
valid control group for CD patients who are.
Moreover, the fact remains that many CD patients
are food sensitive and do improve on an exclusion
diet, a therapy which, although demanding, is
completely harmless when properly followed.
Patients with CD but not UC were found to have
significantly high levels of antibodies to bakers yeast
in blood samples. These results were confirmed
in a later study which also found that raised
antibodies to yeast occurred in CD patients
regardless of whether they were yeast intolerant or
not.100 The pathogenic importance of these findings
has not been established.
Other Factors
A study of the epithelial cells from the small
intestines of CD patients has provided a clue to a
possible major source of immune dysregulation in
CD.101 Phagocytic lysosomes containing lamellar
layers of lipid were found in all patients. It was
proposed that the content of these lysosomes were a
combination of lipid and bacterial fragments.101
Lipids emulsified with bacterial fragments are used
experimentally to create a powerful immune
response known as the adjuvant effect (see Part 1 of
this article). This combination occurring in
epithelial cells could be a strong stimulus to the
pathogenesis of CD and may explain the success of
elemental diets in CD, since they are low in fat.
Foreign bodies can also act as a source of immune
dysregulation. In early studies foreign bodies were
thought to be a factor in CD.102 However, a recent
study found crystalline material infrequently in CD
tissue from only 2 of 20 cases.102 Attempts to
implicate minerals from swallowed toothpaste were
inconclusive.102 However, it may be prudent to
instruct CD patients against this practice.
Leukotrienes and PAF have been implicated as
factors which amplify intestinal inflammation.103,104 It
has been postulated that free radicals may play a
pivotal role in the inflammatory process in IBD.105
Phytotherapy For
Crohn’s Disease
Diet
An individually determined exclusion diet, as
outlined above, is an important part of therapy.
However, if this is not practical, the case history may
provide clues to food sensitivities. In particular,
dairy or wheat avoidance should be considered. If
there are no leads from the history, the most
practical approach is to begin with dairy avoidance.
If after about 2 months there is no improvement and
a challenge does not produce aggravation of
symptoms, wheat avoidance should be tried. Given
the association of yeast antibodies with CD, all CD
patients should avoid yeast, whether they are
sensitive or not. A relatively low fat diet may also be
prudent, and patients should be warned against junk
food and recycled cooking oil.
Bowel Flora Regime
A correction of bowel flora in CD may reduce the
dysregulation caused by an abnormal flora, and
could also create an unfavourable environment for
intracellular pathogens such as mycobacteria and
viruses. Phytotherapist Hein Zeylstra has developed
a successful treatment regime for IBD. The regime is
outlined in Table 1. This approach originated from
the naturopathic approach to Johne’s disease in cows
described by Roger Newman-Turner senior.
Although Hein Zeylstra provides no explanation as
to why this approach may work, it is my
interpretation that the regime has a favourable
influence on bowel flora.
Clinical
Basically, the routine is to periodically fast, taking
fresh garlic (Allium sativum) and slippery elm
(Ulmus rubra). Pathogenic bacteria in the bowel
lumen would be weakened by fasting, since they rely
on a ready source of nutrients. The garlic then
reduces the population of all bacteria in the bowel
lumen, and the slippery elm encourages only the
growth of favourable bacteria. This last aspect of the
therapy is because favourable organisms such as
Bifidobacteria can utilise the mucilage in the slippery
elm as a food source, whereas pathogenic bacteria
cannot. Thus there is an increase in favourable
bacteria. If the routine is repeated several times over
a few months, a “normalisation” of bowel flora will
result. According to Zeylstra the regime works faster
in CD than UC, possibly because of the favourable
effect of fasting on CD.
Herbs For CD
Immune enhancement with herbs such as Echinacea,
Picrorrhiza and Astragalus will help resolve the
presence of measles virus, mycobacteria and
abnormal bowel flora. The measles virus is
enveloped, so hypericin found in Hypericum would
be active against this virus. Hypericum has also been
shown to be active against mycobacteria in vitro.106
Other herbs with such in vitro activity include Allium
sativum and Cinnamomum zeylanicum.106 Berberinecontaining herbs such as Berberis species and
Hydrastis have a good broad-spectrum antimicrobial
activity and are useful to help correct bowel flora.
Matricaria is useful for the symptoms of spasm and
together with Calendula will help to repair a leaky
gut. Because of the leaky gut, phagocytic screening
by the liver should be increased using Echinacea and
Silybum. Anti-inflammatory herbs which inhibit
leukotriene production such as Zingiber are also
indicated. Cell-mediated immunity is a factor in the
pathogenesis of CD, so selective use of Tylophora 1:5
(2 mL per day for 10 days of each month) may be
useful in the early stages of treatment. As with all
autoimmune diseases, best results come with longterm treatment.
Case History
Female patient aged 39 years. She had CD for 15
years (for 10 years her condition had been diagnosed
as UC). Symptoms probably associated with the CD
included an inflamed left knee and a skin rash.
She had been in remission for 3 years, but about 6
months ago a relapse occurred. She was passing
motions with blood every half hour (no wonder she
had been diagnosed as having UC). Conventional
medication had not been prescribed, as she reacts
badly to drugs. History-taking revealed
endometriosis, treated by laser. Her appendix had
been removed about the time of the original onset of
CD and it was rotten and abscessed.
Given the history of appendicitis, emphasis was
placed on lymphatics and regulating bowel flora.
Treatment consisted of a dairy exclusion diet,
slippery elm (Ulmus) 4 teaspoons per day, and fresh
garlic (Allium sativum) up to 2 cloves a day. The
bowel flora regime was not followed.
In addition, a typical herbal liquid prescription
consisted of (based on 1 week):
Herbal Formula
Calendula (Calendula officinalis)
1:2
20 mL
1:2
32 mL
Poke Root (Phytolacca decandra)
1:5
3 mL
1:2
10 mL
1:3
15 mL
Meadowsweet (Filipendula ulmaria) 1:2
20 mL
100 mL
After 3 months there was a 90% improvement. The
skin rash and joint pain were gone and her motions
were normal. She noted her hair had become glossy
- attributed to better nutrition. Deviation from the
dairy-free diet caused exacerbation. Patient’s
comment: “Why doesn’t my doctor know about this
sort of treatment? In 15 years no-one ever
mentioned anything about diet.”
Clinical
Day 1
Days 2
and 3
Day 4
Days
5 to 14
Day 15
Fast - no food, but water and
medicines are allowed.
Continue as for Day 1. Twice during the
day take one to two cloves of crushed
fresh garlic with a copious quantity of
water. This has the effect of flushing
the fresh garlic quickly into the small
intestine. At different times take one
to two teaspoons of slippery elm
powder with copious water.
Gradually introduce allowed foods
and continue with medicines and
slippery elm.
Follow exclusion diet and take
medicines and slippery elm.
Begin again as for Day 1 etc.
Table 1: The Bowel Flora Regime as developed by
phytotherapist Hein Zeylstra. This may need to be
followed for several months.
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A PHYTOTHERAPEUTIC PERSPECTIVE Clinical

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