Leprosy Mailing List – May 18th, 2007
Ref.: A complicated
case of recurrent erythema nodosum leprosum reaction
From:
Warren
G., Chatswood, Australia
Ref.: Dr Osahon Ogbeiwi’s message, LML May 12th, 2007
Dear Osahon,
Greetings-
wonder if you have been following the various emails on
reactions over the last few months? I guess so.
Reaction Type 2 (also called ENL reaction) is
always a problem and I am afraid that the WHO recommendations of
prednisolone so freely, have produced many problems.
For your patient.
I think the clue is in the various other
medical problems. I note
he has a gastric ulcer- so that MUST be protected and treated, make
sure he always has gastric protective supplements with every dose of
his prednisolone, if he has had gastric haemorrhage it is
essential that he gets his haemoglobin and iron stores up- if
necessary he may needs a transfusion.
I have found many patients with severe ENL who
tolerate all the fancy treatments for reaction without any real
improvement, until a blood transfusion then off they go, and suddenly
get better. (Yes I know blood transfusion are not always available –
then give intramuscular iron etc!, and the vitamins and minerals.)
Epileptic fits- do you know the cause? The fits – why? Did he have them before the
leprosy? Could he have had a meningitis or perhaps cerebral malaria or
something (?) that certainly needs investigating. Has he only had fits since
March or was it before the ENL? Phenobarbital in fairly high
dose will often reduce the severity of ENL- and certainly should
help control the fits. I
have often used it for that- especially in small children as long as
the Phenobarbital does not make the patient fighting mad as it sometimes
does!
Yes, check the stool for parasites- but even
more important check for any other chronic infection- I have found patients
who have had typhoid earlier that was ever completely treated and when
checked it was found that the blood titres for typhoid were very high. Give a full max course of a
suitable antibiotic to eliminate the infection that may be lurking in
the liver and within a month the blood titres will come down
and the ENL will be far less. Malaria
too- make sure he is adequately treated. What else is likely in
his area. Has he chronic
liver disease – that is more difficult as that could limit the doses
of other dugs that you can use. TB,
kidney is another common stimulant of ENL!
Why has he severe back pain- Is it only that the fits
cause severe muscular overactivity-
Has he any other definite pathology of the spine. If that is so then it is the
medical control of the epilepsy that will be crucial. Pity you cannot give Aspirin
as that alone will often control milder ENL, but not with a
gastric ulcer! Does he
need rectal suppositories while getting the gastric ulcer
controlled. And Aspirin at 600mgms daily is often adequate to
control the minor varieties of ENL.
It is an anti-inflammatory as well as analgesic- and
paracetamolo is not as good a anti-inflammatory.
Find any other medical problems- Is he diabetic? He may
well be testosterone deficient if he has had severe ENL for a year.
If he has been on prednisolone for 12 months then we have
to assume that the rifampicin has really been able to really reduce
the numbers of bacilli by any great degree.
If I were looking after him I would
concentrate on getting him off the prednisolone by using high
dose of clofazimine without dapsone or rifampicin and use of lots of
chlorpromazine and everything else I know of to deal with any
other medical abnormality and to help support his general body
functions.
Check his Liver functions as if he has
liver problems you do not want to be using largactil (chlorpromazine
). Check his kidney
function and Hb and record his inflammatory markers.
Give clofazimine 300mgms daily with food (in the
old days we actually gave a spoonful of oil with each dose but the
newer capsules incorporate enough oil to ensure absorption). It will take 8 weeks to build
up its maximum anti-inflammatory effect. What is his weight. In Hong Kong I have one
massive 200Kgm man with chronic ENL that requires 600mgms daily to get
him well controlled! He
also had TB and the ENL regularly developed pustules so much so, that
he panicked my Chinese staff who thought he had small pox!. Carefully
check temperature chart 4xday as it often indicates a deeper
infection. TB of kidney needs
to be looked for and if he has any foot ulcers they need complete rest
in Total contact case to reduce infection and inflammation.
Now he is in Hospital. Adequate fluids- ideally monitor urine output- he needs at least 2 liters out
every day! May be best
for the nurse to supervise he drinks at least half a glass of some
fluid every hour x 16 per day plus his meals which incorporate
soups and extra tea etc. He needs this for his kidney function
and to have fluid for sweating etc.
Ensure good diet with extra proteins lot of eggs if nothing
else. Or milk- Dry milk powder can be mixed
into food if needed or given with chocolate drinks! The Chinese will not drink
milk but love chocolate and chocolate drinks! Needs meat for iron, or extra
tablets etc. Give the vitamin supplements in the notes.
Ensure no constipation, give extra fibre such an
phsyillium husks, or they will have their own local variation. Constipation encourage
absorption of unwanted toxins.
The next most important requirement is physical
and mental sedation! And I mean that. He should not have
any responsibilities while getting things organised and once
stabilised it is good to give him something to do to make him feel he
is still a useful person and not dependant of everyone else to look
after him. NO NOT VALIUM
that does not really have a good effect. Phenobarbital should be enough for milder cases but in
your case I would say high dose Largactil. And I mean High dose.
If he is of about 65-80Kg and has reasonably decent Liver function
tests, then I would start on 100mgmsd Chlorpromazine 4 time
daily maybe Tds and nocte! Yes I can hear you gasp- It is
marvellous- that does makes the patient almost a walking Zombie. He spends most of the day
resting or sleeping- but can be woken for meals and bath
and toilet etc. For the
first 3-4 days he will spend most of the time asleep but by the end of
the first week he has learnt to live on that dose. At that stage, organise that
he does a regular exercise session, walking or a stationary bike, and
hand and foot maintenance exercises.
He is worried, even if he will not admit it about his future
and family. Valium is not
adequate. If he cannot
take Largactil them Meprobromate (much milder) may help, or
Amytriptaline again as high as 50 mgms tds (!) in the early stages;
but recommendations are to start at 75mgms daily though in hospital it
may be good to go to 100mgms. But
extra high doses can give epileptic seizures. So may need to be
careful. I find it is
very good for milder cases to cut the depression when they cannot take
largactil. We used to use
good old Potassium Bromide and Chloralhydrate in the early days before
largactil became available and everyone turned up their noses at the
old Pot Brom! It
certainly helped hundreds of patients sleep at night. Yes, make sure he has enough
of something to sleep through at night. You can usually
start dropping the largactil at the
end of the first week – by that time the patient will be more
relaxed!
In your letter you say he is on 15mgms
prednisolone but still has nodules- are they really ENL nodules or
leprosy nodules? I
suspect the latter because the Rifampicin has not really been able to
eliminate a large proportion of the bacilli so the disease is still
spreading as the prednisolone minimises the healing by fibrosis that
occurs. I saw a similar
case in Melbourne last month and on biopsy the “Nodule” did not
show any evidence of reaction it was purely a “new nodule of
active LL disease” in patient (similar to yours) who has been
on and off prednisolone for years and has testosterone deficiency
and lots of other problems.
The Clofazimine does not dramatically kill off
the M leprae so there is not a sudden increase in Antigen as
there is when Rifampicin kills masses of bacteria, but it is
definitely bacteriostatic and bacteriocidal! So it is therapeutic, at may be a slower rate, but it is also
anti-inflammatory and it is the inflammation we are trying to combat.
IN treatment we are trying to reduce the
severity of the ENL we do not mind if there is still a little ENL; it
shows the body is still trying to eliminate the disease! Do not aim to
eliminate all ENL a little does not matter it is better to get off the
prednisolone and onto high Clofazamine.
So for the first couple of weeks he is on Clofazimine
300mgms daily, perdnisolone 15mgms, Largactil (or similar) 100mgms
3-4/day, sleeping well, plenty of fluids not constipated-
eating a reasonable diet- or at least drinking suitable protein etc.
If he will not drink I put an intragastric tube down his throat
– can give proteins then not just fluids as by IV which always
presents problems- (do not give your self the problem of trying to
maintain good electrolyte balance and protein by IV fluids- it is a
danger to the patient as well as a lot of work for your staff and the
patient needs to learn he must feed himself for life!) In Hong
Kong we soon found that a NG tube was only needed for a few days and
then the patient decided he would drink! Much more pleasant and
for us, cheaper, better food content and not so difficult to maintain.
Treating any other disease at the same time. Esp the convulsions.
Then try and drop the prednisolone to 12.5 mgms
and if Ok after one week, may be able to reduce the largactil to
say 50mgms tds and 100mgms at night.
Keep for 2 weeks and then try and drop prednisolone to 10mgms
daily.
Watch - get him exercising by now please. If the ENL returns (be
sure they are ENL and Not just new nodules) then put the
prednisolone back to 12.5 and get the nurse to crush the
prednisolone tablets and mix them with Vitamin c 50-100mgms so and
the nurse puts the crushed prednisolone on the patients tongue so he
does NOT Know how many tablets he is being given. (She also gives all his
medication the same way (on to his tongue not of necessity crushed!)
so he does not know when alterations are being made, in any tablets.)
Our patients are not fools! I have many patients who had
worked out that when they had 4 prednisolone tablets they felt
good but when it was three they did not feel so good so would go
back to “feeling aweful” even if not ENL. The staff would fall for it
and increase the prednisolone again- Hence the use of the emotional
stabilisers- largactil or amytriptaline). But crushing the
tablets with Vit C to mask the flavour they did not know and we
completely fooled them! One
migrant (Chinese) patient in Sydney got ENL (she said) everytime
they reduced the Prednisolone-
I guessed that she did not need prednisolone but was scared
that anyone would know she had Leprosy and shun her [leprosy has
such a bad social stigma where she came from]- so we started her
on the Amitriptaline, and then arranged for the local Chinese church
to go and take her out and make her welcome. No problems in stopping the
prednisolone and never any more problems!
Now start reducing the largactil.
You will slightly alter the dose each day, or second day probably
better at first. Patient
is on 50mgms tds and 100 at might- Ok, reduce the one dose every
second day ie 50 down to 25 for midday then do evening two
days later and then am- 2 days after that then the nocte 50 then the
next week it is cut the noon the evening and the am in that order
but not the night dose (Make sure the patient sleeps on the reduced
night dose if not add something else to make sure he sleeps, Keep him
on that reduced levels for say a week then increase the largactil
again to the 50 tds and nocte, one day and decrease the prednisolone
10mgms the next day! Fool
him! Keep him on that level for a week and if Ok repeat the
reducing scheme-
Yes, it is a slow job you will reduce the
prednisolone may be by only 2.5mgms per time about once in 3-4
weeks but hopefully will be able to get to the end of the prednisolone. [Yes I agree in mild cases you
will be able to reduce quicker- but that depends on your judgement and
you staff and getting all intercurrent medical and emotional problems
sorted out!]
The Clofazimine keep on 300mgms at last the
first 8 weeks- If he has
no undesirable abdo symptoms continue till get the prednisolone
down the say 7.5mgms AND stable and all other pathology
dealt with- then drop Clofazamine to 250mgms daily for say 3
months ands then to 200mgms daily.
Continue the largactil for many months after off all prednisolone
and chlorpromazine is down to 200mgms- The Largactil can be
slowly reduced to just 50mgms nocte once the prednisolone
is stopped for say 2 months and there is no return of ENL.
It is essential to maintain the largactil in
maintenance dose for at least 6 months after no ENL when on
Clofazamine 100mgms daily. And
BI well down, but monitor the Liver function as hepatitis is
not an uncommon complication and Aids does not help. Are either suspect? But
before stopping the Largactil completely get him onto Rifampicin and
Dapsone = only add one at a time- say 3 months apart so you can
see if either produce problems. Can
probab start adding Rifd when off prednisolone and still on
largactil tds. Once onto the three drugs MDT- you can start
counting the months of MDT- Not while on the prednisolone. In his case I would give say
24 doses MDT and then continue the Clofazimine till he is skin smear
negative in three sites (widely separated i.e. face, trunk and leg!)
each time taken 3 months apart! We do not want a relapse or
re-infection.
In the old days we often gave these patients
ACTH to stimulate the adrenals glands as the high prednisolone levels
suppress normal Pituitary production.- But I agree that is a problem
to be remembered. Supra-renal
supression and reduced testosterone due to involvement of the testis-
You do not mention the BI? I would not
expect it to drop by any appreciable amount while on the prednisolone
It often does not.
You speak of enlarged ulnar nerves. Yes
they will be, that is just a result of his reaction and as the
reaction is controlled the swelling will decrease. You do not mention if large
and soft or large and hard. Once
he has had LL for a number of years the nerves may all become large
and harder than normal.
AND ARE NOT GOING TO REDUCE MUCH AS IT IS DUE TO THE NORMAL
HEALING BY FIBROSIS. No
the prednisolone is not aimed at drastic reduction of them. I am afraid you must realise
that the damage has already been done to those nerves and it does not
really matter that we do we will not prevent the natural healing by
fibrosis that will occur- Yes
the prednisolone may delay the hardness but the neural deficit will
eventually occur and we are not going to stop it. It is far more important
to get him off the prednisolone for the sake of the rest of the body. What are the use of
functioning nerves if he is other wise a physical wreck! But
make sure he does the maintenance hand exercises as in MY book on
neuropathy in order to maintain function as long as possible and
prevent stiffness.
Grace Warren
