Leprosy
mailing list, July 9th, 2005
To: all.
Ref.: reactions
From: G Warren, Sydney, Australia.
Dear Salvatore,
I have been reading some old emails and came across this article by
Ben Naafs from 2003 on lepra reaction (ENL), at the end he
makes these excellent comments.
This is just the relevant end of the article (19.8.03).
- "Colchicine, which inhibits vascular injury in experimental
Arthus reactions by inhibiting the chemotaxis of the neutrophils, has
been shown to have some effect on ENL. However, the results are not as
impressive as were claimed in the initial trials.
Ciclosporin A has been shown
by some to be effective in severe ENL and may be a substitute for
thalidomide in affluent societies. Although thalidomide is more
effective, it frequently cannot be used due to restrictive political
legislation. However, during field trials, ciclosporin A was of little
benefit in preventing ENL, indicating that ciclosporin A may be less
effective in suppressing the Th-2 type CD4 cells than the Th-1 type
CD4 cells involved in the reversal reaction.
A strong anti-ENL effect has
recently been claimed for pentoxifylline when it has been administered
in high dosages. Other researchers, however, were not that impressed.
It was tried because some investigators were of the opinion that TNF-a
is of major importance in ENL and pentoxifylline is known to
effectively suppress its production. However, TNF-a is also present in
RR and here neither thalidomide nor pentoxifylline are of much help,
although pentoxifylline also diminishes the leukocyte adherence.
It has been shown that
immunotherapy using BCG in conjunction with M. leprae, with M.
vaccae, M."W" and the ICRC bacilli, was able to
reduce the frequency and severity of ENL. More research should be
directed at the mechanisms involved in this phenomenon; controlled
trials to study its clinical effects should be done especially as some
patients with chronic severe ENL are not properly controlled with the
therapies presently available.
Newly developed treatments for
rheumatoid arthritis may be of use in ENL; however, as yet trials must
be instigated.” -
I would be interested to know
if any research has been done as he suggests on mechanism of BCG
as he mentions, and on ciclosporin and pentoxifylline I
wonder if his article can be republished in the light of all the
articles you have had over the recent years on ENL. As you know I get
around and I have been troubled for years by the number of deaths
I see in patients who are either on steroids or who have had steroids
for long periods for ENL.
In many instances I feel that the dose and duration of the steroids is excessive
for as Ben Naafs says it is episodic and steroids ought to be titrated
to the actual daily needs. I personally find that most patients can be
managed, long term at least, without steroids, often just by high
dose of clofazimine (I had an article in leprosy review (in about
1968) on this!
I have found too many patients
dependant on steroids. In western countries it may be fair enough, as
emergency medical treatment is usually available if required- but in
third world countries this is not the case. I have seen patients die
because they got flue or severe diarrhoea or some other infection or
accident, not to mention things like TB and diabetes in the
twelve months after the steroids were officially stopped but obviously
their own immune system had not recovered. Sometime seen by local
doctors who did not realise the severity of the problem or who did not
even know they had been on steroids.
Unfortunately in a number of cases the ENL is exaggerated by
a chronic infection which is hidden by the steroids and until found
and eliminated the ENL continues! Yes, TB is common,
urinary tract infections and infected foot ulcers. Also
interesting, in Asia especially, is the incidence of chronic
sub-clinical typhoid that can be diagnosed by doing the blood titres.
If the titres are high and there is suspicion, a good course say
3-4 weeks of the locally potent antibiotic (used to be chloramphenicol
- then ampicillin) results in goodbye to ENL.
One small boy had a titre on
1/2400! And ENL for several years- history revealed a part
treated typhoid 3 years previously- one month on ampicillin and
titre fell amazingly and no more ENL for many years!
These are facts that many
people do not know and could I am sure help hundreds in the less
well financially endowed world where things like thalidomide are illegal
and it is so expensive (one letter from India tell me it costs $2-3 US
per tablet) if it can be legally imported.
In some old LL patients the chronic ENL is a direct response to the
chronic infection in their foot and hand ulceration that has come from
the loss of sensory perception caused years earlier. Cure the ulcers and teach self
care and the ENL goes; then hopefully their body can build
up its immunity again to be able to cope with the next generation of
ulcers!
This is one of the problems of treating Leprosy in General clinics.
The Doctors are so busy they do not have time to thoroughly
investigate the leprosy patient’s problems and just dole out
steroids as they make the patient feel good- and appear better quickly!
Even here in Australia steroids
produce all sorts of side effects. One patient (an immigrant from an
endemic country where leprosy is much feared) had been on
steroids for 3 years after ENL and it was stated that every time they
tried to drop the steroids she got a new crop. On careful query we found
it was an emotional problem - She was afraid that if anyone in her
block of flats found out she had leprosy she would be ostracised! The other residents in her
block were Aussie and prob would not recognise leprosy if they fell
over it. Certainly were not afraid of it! On careful questions I
found she had had leprosy for 20 years- not the official 4 years in
her charts- that was the duration of her treatment. We put
her onto chlorpromazine as Ben Naafs mentions and increased the
clofazimine and weaned her off slowly the steroids, we
also arranged for some members of a church in her own racial
group to befriend her and take her out and she never had any
more problems with ENL!
It is a complicated problem.
Never forget the possibility of an emotional background to ENL.
Never forget the " high" that steroids can give. Any person who has had
steroids for a long period feels an emotional down when the drug is
stopped and needs something to bridge the gap or else they complain
they feel awful and the steroids go up again especially if the doctor
is not used to reducing steroids for ENL. I had not realised this till
one of my American colleagues who had been having steroids for years
for a non life threatening complaint (was it allergy or arthritis
I cannot remember) but she confided to me how terrible she felt
for months in spite of alternate therapy once the steroids were
reduced and eventually stopped. Also the steroid high can make the
patient ignore the paraesthetic sensations which seem to increase
as the steroids reduce and are often interpreted as active neuritis!
Also if nerves are recovering they also produce paraesthesia and it
takes careful checking to be sure one is treating recovering nerves
which should not need steroids if the patient has had adequate anti
leprosy drug therapy.
While on that topic has anyone ever properly
assessed the effect that steroids have on delaying, on slowing the
effect of MDT on the bacterial populations? From my years in Hong Kong
I state that one does not count the months on steroids as months of
MDT. Yes, they need the MDT while on steroids but should not have those
months included. Hence if a multibacillary (MB) patient has 6
months steroids for Type 1 reaction he ought to have 24 +6 months MDT
(at least; but I would prefer to continue the MDT till he is skin
smear negative!). I have seen too many BB, BT type MB patients relapse
after MDT is stopped even at 24 months!
I do not know if you want to publish all this, you are welcome.
Certainly it could help some of the younger workers. But please ask Dr
Naafs my query and/or give me his address.
Many thanks for your help.
Grace Warren
