of 21 /21
AGW\Reactions\2006 Leprosy Mailing List – January 11 th , 2007 Ref.: Reactions in leprosy From: Warren G., Sydney, Australia REACTIONS IN LEPROSY. by Dr Grace Warren, revised 2006 In leprosy, a reaction is an acute exacerbation occurring during the course of the disease. It is a very loose term for a number of conditions, mostly inflammatory. It is important that the difference in these conditions be understood so that the correct management can be given. TYPE I Reaction. Type I reaction is an example of Type IV hypersensitivity (allergic) reaction (Coombes and Gell.). This is due to a change in the place on the immunological spectrum. It is possible for the immune response to the disease to improve, i.e. to move up towards Tuberculoid end of the spectrum and a more efficient immune response which is called " Upgrading" reaction. There is also the possibility of a " Down grading" reaction when the patient seems to loose his immunological potential and the disease becomes less localised and tends towards the lepromatous pole of the spectrum. These two distinctly different reactions are often linked together as " Reversal reaction" because they have some similar clinical manifestations. Reversal reaction implies that the immunological process was moving in one direction and then changed direction and reversed! While this may be the case in some BT leprosy patients who initially were downgrading without treatment and then once therapy was commenced they commenced to upgrade- so the patient's response did indeed reverse. But this is not always the case. Hence it is better to call them both Type I reaction and subdivide as Upgrading or Downgrading as needed, if relevant. A patient with a “Down grading” reaction will usually be a patient who is not on treatment or in whom the treatment is ineffective. It may 1

morbus hansen

Embed Size (px)

DESCRIPTION

reaksi morbus hansen

Text of morbus hansen

AGW\Reactions\2006Leprosy Mailing List January 11 th , 2007 Ref.: Reactions in leprosy From: Warren G., Sydney, Australia

1

REACTIONS IN LEPROSY. by Dr Grace Warren, revised 2006 In leprosy, a reaction is an acute exacerbation occurring during the course of the disease. It is a very loose term for a number of conditions, mostly inflammatory. It is important that the difference in these conditions be understood so that the correct management can be given. TYPE I Reaction. Type I reaction is an example of Type IV hypersensitivity (allergic) reaction (Coombes and Gell.). This is due to a change in the place on the immunological spectrum. It is possible for the immune response to the disease to improve, i.e. to move up towards Tuberculoid end of the spectrum and a more efficient immune response which is called " Upgrading" reaction. There is also the possibility of a " Down grading" reaction when the patient seems to loose his immunological potential and the disease becomes less localised and tends towards the lepromatous pole of the spectrum. These two distinctly different reactions are often linked together as " Reversal reaction" because they have some similar clinical manifestations. Reversal reaction implies that the immunological process was moving in one direction and then changed direction and reversed! While this may be the case in some BT leprosy patients who initially were downgrading without treatment and then once therapy was commenced they commenced to upgrade- so the patient's response did indeed reverse. But this is not always the case. Hence it is better to call them both Type I reaction and subdivide as Upgrading or Downgrading as needed, if relevant. A patient with a Down grading reaction will usually be a patient who is not on treatment or in whom the treatment is ineffective. It may include patients who are resistant to the drugs they are taking or who are not compliant and hence not taking the drugs as ordered. Downgrading reaction does not really occur in patients on effective Drug therapy, unless they have some other severe illness. There is also another clinical condition that is commonly grouped in with Type I reaction as an Upgrading reaction. This is sometimes called the "Reaction of Healing" and occurs in a patient who has developed a small patch that may have had Indeterminate characteristics (or may have been so vague as to have escaped notice), and then as he develops his full immune potential the lesion becomes hot, swollen and inflamed exactly as a regular Upgrading reaction does. There is strictly no change in the immunological place on the spectrum- previously the patient had not developed his full immune potential and he is now pushing active histiocytes and lymphocytes into the arena to kill the M. leprae. It may look like a Type I reaction and the management is basically the same but, it can only occur early in the disease as the immunity originally develops, and so is not a true change in the position on the Immunological spectrum. It is the demonstration of the full development of the immune potential.

AGW\Reactions\2006

2

TYPE I reaction basically presents as :Some or all LESIONS show signs of ACUTE INFLAMMATION - pain, tenderness erythema or oedema. NECROSIS or ULCERATION, in lesions, in severe cases. DESQUAMATION may occur even in the acute stages- more frequently as the lesions subside. If NEW LESIONS occur in downgrading reaction they will be less well defined than previously, and there may be many of them. They may also show AFB when these have previously been reported as absent. Occasionally new lesions appear in Upgrading reaction, if so they will be more well defined than the original lesions and are usually few in number. SYSTEMIC symptoms are rare unless there is a massive reaction involving very large areas of the body and limbs. NERVES may be acutely involved. Typically one or more nerves become acutely swollen with possible pain and/or tenderness at the sites of predilection and an acute neural deficit. However, frequently there is no pain or tenderness in the affected nerve and the involvement of the nerve is known by the loss of neural function. This is silent neuritis, and it may occur without marked involvement of skin lesions. ( this must be checked for at every visit by sensory testing and basic VMTs. Typically one nerve is affected in True TT leprosy and many nerves in Borderline. Several nerves may be affected at one time, but it is also possible to have a succession of nerves becoming affected serially over several weeks, in BT or especially in BB leprosy. OEDEMA of lesions especially those of face, hands and feet may occur, especially in the type 1 reaction of BL or even LL leprosy. The changes in Type I reaction may occur quite rapidly. It is impossible to rely on the patient to tell if there has been a change in the size shape and number of lesions. Also he cannot tell if there has been real loss in nerve function. Hence it is important that every patient should be thoroughly charted on admission. All skin lesions ought to be entered on a body chart paying careful attention to the size and shape and position of lesions in BT and TT patients where there are relatively few lesions and it is easy to chart each one fully. Nerves also ought to be carefully checked and recorded, with regard to size, hardness or softness, tenderness or pain. Each nerve ought to be listed separately so that it is possible to be sure of what is happening (or what has happened) when the patient is reviewed in the future. If a nerve that is examined is normal this MUST be entered. It is important that the status of all nerves be charted. Motor power and sensory tests should be carried out AT THE FIRST VISIT, to provide a base line. If no adequate charts are made at first visit, and every time there is a real change in the patients condition, it will be impossible to assess if the patient really has a reaction or not. Yes, this is time consuming but there is no short cut to diagnosing reaction, or relapse or reactivation, and early diagnosis is necessary if deformity is to be prevented. There are many dangers in use of Steroids and we SHOULD NOT order them if not really necessary. The patients long term future quality of life depends on how well we treat him initially. It is rare that the clinician can determine the severity of the reaction at the first visit. The patient may well not tell the whole story or the truth and one must observe carefully the progress before determining the severity PLEASE PLEASE never start steroids at first visit with reaction. In the reaction of healing there will obviously be an acute "flare up" in the lesion only, and the patient is usually a new one. If a patient comes in complaining of anaesthesia you need to be able to determine if it is "NEW" or if there has already been some sensory deficit there before and for some reason the patient

AGW\Reactions\2006

3

has only just noticed it. Again, a patient may come in and complain that he has JUST lost the use of ring and little fingers (due to ulnar nerve involvement). On examination he is obviously unable to use those fingers correctly but, on checking a previous examination you find that over a period of months the lumbricals and interossei have slowly lost power. It is NOT an acute type I reaction neural deficit. Or you may find that some months ago he had normal power and sensation, but a many months ago there was reduced sensation and then a few months ago there was definite weakness, perhaps even loss of all interossei and lumbricals but the patient had not observed it because of the rare need to fully straighten the fingers, unless he has been taught to do the proper exercises. These should be taught to every patient with any suspicion of nerve damage. But with the wasting of the muscles after the neural deficit, the atrophy has made the hand look thin; also the imbalance of the other muscles is now pulling the fingers into a deformed position. It takes 6 weeks (or longer) from the motor neural loss till the muscles become clinically atrophied. The patient may not be aware of the motor loss but may be aware of the atrophy and the deformity. If exercises are instituted before the atrophy is enough to produce deformed function it is often possible to maintain adequate function. When patients complain of " Pain" in limbs it is essential to determine what they mean. Is it true pain or discomfort due to paraesthesia, numbness or just the funny feeling of no feeling! Many patients with long term anaesthesia have been over-treated as though they had an acute reaction because they complained of pain which was really only a type of the paraesthesia due to the long term neural deficit, but which had never been adequately recorded. Nerves in leprosy are parasitized early and show pathology on careful examination long before there are any clinical signs of neural deficit. Most LL patients with a skin smear of 3+ or higher will have some nerve fibrosis when diagnosed but no obvious clinical loss of sensation. Skin Smears may fall rapidly in type I upgrading reaction or in the reaction of healing (but must be taken right on the active edge of a lesion). In early Downgrading reaction there will be an increase in the bacteriological index (BI). Though actually the BI rise probably occurred before the lesions appeared red and inflamed. If a patient appears to have a type I reaction when he commences therapy it may be difficult to be sure if he is spontaneously upgrading (as frequently occurs due to reaction of healing or spontaneous changes in the immunological status as may occur if he has been successfully treated for diabetes or Tb or other intercurrent disease so that his immune system can now concentrate on the leprosy) or if he is downgrading. The Histology changes precede the clinical changes by several weeks or even months. Hence it might not always be possible to tell if a patient is in an upgrading or a down grading reaction on the first visit. TYPE II REACTION. Anti-body/anti-gen reaction. This is the humoral hypersensitivity reaction, it is an example of Type III hypersensitivity reaction (Coombes and Gell) not associated with any change on the immunological spectrum. It is often called ERYTHEMA NODOSUM LEPROSUM (ENL) from the rose pink nodules which may develop anywhere on the body and show the sites of the anti-body\anti-gen\complement reaction that causes a vasculitis as the basis of the nodular inflammatory lesion. While ENL is the typical lesion in many type II reaction patients it is by no means the only manifestation. Many patients develop sheets of inflammatory lesions, forming a brawny induration. Others complain mostly of arthritis. neuritis, orchitis, iritis, osteitis. Type II reaction is characterised by :Crops of Rose Pink Spots (ENL), occur at about 10 day cycles, and each crop lasts 2-10 days. The ENL can coalesce or become sheets of induration. They are in the existing skin lesions and contain large numbers of polymorphs and dead M. leprae. Crops may overlap so that patients may have nodules at various stages, at the same time. Initially the ENL may be somewhat tender

AGW\Reactions\2006

4

and eventually fade to a dirty brownish or greyish patch. They may become vesicular, pustular, bullous, or ulcerative. They may be the first definite manifestation of leprosy as the initial skin patches may be so vague as to not attract attention. Many patients have been admitted to general hospital wards with Erythema Nodosum for investigation. But in Leprosy ENL may occur anywhere on the body, in erythema nodosum due to other causes, it is usual for the lesions to occur only on the shins. If a slit skin smear is done, granular leprosy bacilli should be found in the ENL. The antigen\antibody reaction can only occur where there are dead bacilli, i.e. where the antigen has been liberated. IT IS IMPORTANT THAT AT THE FIRST VISIT THE PATIENT BE CAREFULLY QUESTIONED ABOUT THE PREVIOUS PRESENCE OF ENL. If they have already been present we know that he is already sensitised to the leprosy antigen and will be likely to flare up with active ENL as soon as we give the first effective drug that kills M. leprae and so liberates more antigen. Sheets of infiltration may occur instead of discrete ENL. In BL leprosy the ENL occurs only in the skin lesions and the apparently unaffected skin has no ENL. FEVER and MALAISE are common and in severe Type II reaction the patient may be very toxic and/or anaemic. OEDEMA of the face, hands and feet may occur, but not as commonly as oedema in the lesions of extremities in Type I reaction. PAIN may be diffuse or confined to nerves at sites of predilection. It may also include muscle pain, eye pain (iritis), bone pain (especially tibia), lymphadenitis, epididymo-orchitis, arthritis, synovitis. NERVES may be swollen and tender, sometimes very painful but the nerve is more often large and hard indicating a chronic fibrotic condition, which implies that loss of nerve function is not likely to return. The patient with a severe Type II reaction can present a real picture of misery. In the old days such reactions often lasted for months or years. It is desirable to carefully assess the patient for: 1, Severity of Type 2 reaction, method of treatment depends of severity. 2. Cause of the ENL. Do not accept leprosy- there is usually some precipitating cause that we can treat, that is actually precipitating the reaction. Mild Type 2 Reaction consists of some ENL but the patient does not have a lot of pain or discomfort, and does not have a significant amount of fever. It is often regarded as of nuisance value and has an advantage that it indicates that the patient's own immune system is at least trying, even if ineffectually, to control the infection. Mild ENL can often be completely controlled by increasing the dose of clofazimine (Lamprene); may be to 100-200mgm or even 300mgm daily, for a short period (2-3 months) and then reducing the dose. The lamprene does not remove ENL at once, it takes weeks to achieve the full effect; is the safest and best method of controlling mildish Type 2 reaction. Also give aspirin 500mgm x 3 per day &/or add Largactil or some other tranquilliser at night (not valium). Investigate for any medical, surgical or emotional condition that may be the trigger. AND TREAT THAT PROBLEM ENERGETICALLY! Severe Type 2 Reaction usually shows many ENL and they may be painful. There may be general aches and pains (not unlike Flue) and the patient may have a high fever. Some or many of the lesions may ulcerate and may become secondarily infected (in which case the patient needs antibiotics). The patient may complain of pain in specific nerves. In these cases some time should be taken to try and determine what was the trigger factor that started the Reaction. A vaccination, acute infection (such as flue) active Tuberculosis or other infections, an infected foot ulcer or untreated diabetes have all been implicated. Also inadequately treated typhoid fever may leave residual high blood antibody titres. Until this condition is corrected it may well be impossible to "cure" the ENL. If steroids are given before general investigations are done they may mask the true

AGW\Reactions\2006

5

problem and so the final "cure " is delayed. Is steroids are given in the presence of diabetes or infection and these are not also adequately treated the patient could get worse, not better. DO NOT GIVE STEROIDS AS THE FIRST LINE OF TREATMENT FOR ANY TYPE 2 REACTION. Start off with rest, physical and mental, and plenty of fluids and good diet, proteins etc and vitamins and ensure no constipation and eliminate parasites. The presence of ENL history at INITIATION of anti-leprosy therapy. It is desirable that careful questioning be carried out to determine if the patient has ever had ENL prior to starting therapy. If he has ENL when first seen or gives a history of having had it, it is an indication that he already is sensitised and has sensitised "B" lymphocytes and antibodies. If that is so it is highly likely that the initial dose of 600mgm rifampicin (Rifadin), which kills M. leprae very rapidly and so increases the level of antigen in the patients body, will precipitate a crop of ENL and the patient may decide he does not want any more therapy as "it makes me worse". In these patients it is best to give Lamprene alone at 100mgm per day for 6-8 weeks to build up the anti-inflammatory action of the Lamprene before adding the rifampicin. These two months can also be used to improve Hb and general health in the hope that when he does go onto rifampicin and dapsone (DDS) he will not develop severe ENL. I know this is contrary to WHO recommendations; but we are dealing with patients, not textbooks, and if we gain their confidence initially they are more likely to comply in future and to take therapy regularly. Normally time does elapse between the commencement of therapy and the development of ENL. In DDS mono-therapy it used to be 12-24 months, but after rifampicin it is as short as 2 months as it kills so many bacteria quickly. This is another good reason for not giving rifampicin daily as that rapidly increases the load of dead bacilli and this could result, in a patient who is already sensitised, developing a very severe Type 2 reaction that could have been avoided. Remember, the bacteria only multiplies once in about 14 days, so once monthly doses of rifampicin kill every second generation of bacteria and that is enough to eliminate an infection. Daily is not needed and is basically a waste and more dangerous. We rarely see liver problems and other signs of rifampicin toxicity from monthly rifampicin.

AGW\Reactions\2006CHARACTERISTICS OF TYPE 1 AND TYPE 2 REACTIONS. Type Forms of leprosy Onset Type I Mostly borderline, may be Subpolar LL and TT Upgrading occurs most often at commencement of therapy, but may occur any time. Down-grading in untreated. Cause Clinical changes in CMI. Inflammatory changes in lesions, may scale or ulcerate. May be new lesions. Symptoms unusual. Immune complex syndrome. Antibody\antigen vasculitis ENL in existing skin lesions, crops at 10 day intervals. ENL may ulcerate. Type 2 Mostly LL and BL

6

May be spontaneous in long untreated pts. maybe after 2 months on rifampicin or later as levels on antigen rise.

Systemic Nerves

Fever, pain, malaise common. Patient may be toxic.

Rapid swelling and\or acute Nerves may be painful or may neural deficit. Nerve abscesses. be tender, usually hard, chronic neural deficit. NOT acute. Oedema of lesions of hands and Skin infiltrated rather than feet. oedema, maybe, iritis, muscle & bone pain, lymphadenitis. Nothing typical. polymorph leucocytosis. ESR elevated, increased Gamma globulins. Negative. or slight +ve. May become very chronic and last for years.

Other

Blood

Lepromin test Course

Upgrade may become +ve. downgrade may go -ve. Seldom persists for more than a few months in upgrading. In down grading without treatment gets worse form of disease.

It must be realised that Type I and Type II reactions can occur at the same time in BL cases especially making it very difficult to know exactly what one is treating.

AGW\Reactions\2006TYPE 3 REACTION.

7

I use that term to include a problem that is often mistaken for reaction. It is not really a reaction at all. It is the condition of deterioration due to relapse, reactivation or re-infection so that the patient presents with new skin lesions, and possibly a rising BI in a patient thought to have completed treatment, or possibly to have been well controlled and on maintenance therapy only. These patients often appear to be a downgrading reaction, or even an upgrading one, but on careful examination one's suspicions should grow. Are you sure the patient is taking the drugs as ordered? Are the dapsone tablets soluble (in the past some tablets were so hard they passed through the gut without dissolving!). If the answer is that they are taking therapy then they are resistant to what ever they are taking. On triple-therapy resistance to all three drugs ought not to occur, in the compliant patient. But with the patients who are on mono-therapy it is a very real danger and especially on doses less than the therapeutic dose. With dapsone the therapeutic dose is 12mg/Kg/day, the risk of developing resistance to dapsone is very real, when patients are given low dose mono-therapy. Even as a maintenance drug DDS ought to be given in full dose (usually 100mg /day in adults males. At this dose toxicity is not usually a problem; allergy can develop at any dose). This type of reaction is becoming a very real problem now with the use of MDT for twelve months only. Many patients complete their 12 months and are told they do not need any more medication and are not followed up. Numbers have turned up 2-5-10 years later with leprosy lesions. Is it relapse? Or reactivation? Or re-infection? If the patient was initially an LL or BL as is very common in this part of Asia, it is likely that they were never adequately treated and the bacilli have survived as persisters in the nerves till the drugs stopped and then out they came again! So I guess it is relapse, but the poor patient is much more likely to get Type 2 reaction and to have permanent nerve damage which would have been avoided if he had been given the MDT longer initially. Prior to the WHO push to eliminate leprosy we gave MDT till the patient was skin smear negative x 3 at monthly intervals; but now WHO does not recommend slit skin smears so there are no records of the numbers of bacilli at any stage of the disease and WHO only diagnoses leprosy if there are definite skin lesions so many of the early LL will not be diagnosed till they are far advanced! These patients will often PRESENT AS:a- vague patches or erythematous macules, painless but teaming with leprosy bacilli which may appear anywhere. As time passes the lesions may become histoid or nodular, perhaps even umbilicated. They require full anti-leprosy therapy, triple therapy. If the patient is actually on an anti-leprosy drug at the time of the relapse he should never again be given the drug that he was taking when the " relapse occurred". It may be advisable to give second line drugs for safety. b-An INCREASING NEURAL DEFICIT with or without pain, so may be mistaken for Type I reaction in the nerves alone. It is essential that if in doubt they ought to be treated with full triple therapy again and if there is a definite new neural deficit, be given steroids for about 3 months, as well as the triple therapy. BUT DO NOT GIVE ANY MORE THAN 3 MONTHS STEROIDS in these cases, as for most of them the deficit developed slowly even if not noted in the history and, the nerves are already fibrosed and the deficit cannot be reversed.

AGW\Reactions\2006DIFFERENTIATION BETWEEN TYPE I REACTION AND RELAPSE. Type I Reaction Onset Time Old lesions New lesions Ulceration Scaling Nerves General condition Response to steroids Sudden - often overnight. During treatment or within 6 months of stopping. Some or all affected, become shiny, inflamed. Some may occur. Sometimes. Common as lesions subside. Commonly involved. No change. Good. Relapse

8

Slow, insidious (weeks\months). long after stop chemotherapy usually at least 1 year. May show re-activation. Frequent. Not common. Absent If involved, problems develop slowly. No change, Lesions subside, but recur worse when steroid stopped.

AGW\Reactions\2006CAUSES OF REACTION.

9

Type I Reaction is usually a spontaneous response of the body to improved general health and rising levels of the antigen due to the killing of the bacilli by the "T" lymphocytes or the anti-leprosy drugs. Any therapy that helps with improving the patient's general state of health and well being, in theory, may precipitate Upgrading reaction. This is not a bad thing. In fact we would like to precipitate upgrading reaction in many patients. It could hasten cure provided we can prevent severe deformity.??? Type 2 Reaction is far less understandable. It may be precipitated by: 1 Any intercurrent infection such as TB, pneumonia, infected foot e.g. ulcers, flue, typhoid, GI infection such as amoeba, salmonella, staphs, especially carious teeth! 2. Any vaccinations or inoculations. 3. Any major surgery. Do not attempt any elective surgery on a reaction prone patient. (Type I or Type 2 reaction). 4. Marked anaemia, or other blood dyscrasias. 5. Diabetes or other metabolic disturbances. 6. Emotional problems. Rejection by family, or society, family problems, poverty etc. 7. Changes of weather. Reaction seems more common in spring and autumn than in summer and winter! 8. Sudden changes in drug therapy; including the therapy of other conditions (e.g. diabetes). In reaction prone patients, do not change several drugs at the same time.

MANAGEMENT OF REACTIONS. TYPE I REACTION. Downgrading. This reaction usually only occurs in patients who are not on therapy, or in whom the therapy is inadequate or they have bacilli resistant to the drugs they are taking. Therapy is therefore to get them onto full triple therapy as soon as possible and to keep them there. If the nerves seem large and soft with or without tenderness (or there is evidence of a new neural deficit) it may be as well to give 6-12 weeks of steroids (doses of 30mg daily of prednisolone, as a maximum, is all that is usually needed.) Upgrading. This reaction is usually an indication of an improvement in the ability to produce sensitised "T" lymphocytes and therefore it implies that the patient is now more able to deal with his infection than previously. If the reaction is a MILD one and there is only some erythema and swelling of the skin lesions without any evidence of neural deficit it is enough to continue the full anti-leprosy medication and to add:Aspirin 500mgms x 3-4/day- or paracetamol - 1 gm x 3-4/day if the patient cannot tolerate Aspirin. Many clinicians recommend other anti-inflammatories but remember this may be a long term problem and you are not going to deal with it in a hurry hence it is better not to try and rush things. Before initiating any stronger long term anti-inflammatories it is best to thoroughly investigate the patient re blood picture, Hb and inflammatory levels and ESR, liver function, kidney function, diabetes, etc. Many of these patients go into a reaction because they have some other medical

AGW\Reactions\2006

10

condition that is undergoing change and unless that is treated properly all efforts to control the reaction will fail. Largactil 50mg nocte. This gives good sleep and mental rest as many patients are really worried because they have the disease and there may be other emotional or social problems that are adding to their problems. Other tranquilisers may be effective eg amytriptiline are effective but in my experience Valium is NOT effective, meprobromate may help esp. women in whom the reaction coincides with menses changes. Check the patients diet. Is he getting plenty of protein and vitamins and calcium? Is he adequately hydrated? The Basic principles of treatment are REST, PHYSICAL and MENTAL and adequate NUTRITION. Support the patient while he treats himself! He is trying to cure himself by the reaction. All patients with leprosy ought to receive iron, a good multivitamin including vit B1 at 10mgms and vit C at least 100mgms and calcium. If possible some protein supplement e.g. powdered milk triple strength in chocolate! MORE SEVERE inflammatory response. The skin lesions may be very swollen and tending to ulcerate. Any inflamed Type I reaction lesion on the face must be regarded as a danger sign and the patient given 6-12 weeks steroid to save from possible facial nerve damage. (together with the above therapy as for mild reaction). If the swollen lesions are not on the face and nerves are not swollen it is not necessary to give steroids if the patient can be kept under adequate observation. But it may be necessary to give steroids at short notice so the patients need to be seen and fully checked regularly, preferably more often than weekly. If there is any suggestion that Type I reaction may develop. ACUTE NEURAL DEFICIT This needs to be treated with steroids as soon as possible. 30-40mgms daily is adequate unless the patient has previously had a lot of steroids. It ought to be given once daily in the morning and reduced slowly. Plan a total of 3months steroids (which can be extended if the reaction has not fully settled in that time) or in very severe cases with marked skin and nerve reaction it may be wise to plan 6 months initially. All steroids should be given once daily in the morning when used for reactions in leprosy. There is no need for divided doses and once daily is less depressing on the Pituitary and adrenals. Steroid therapy needs to be in combination with full triple therapy and supplemented by the medication listed under mild reaction. The correct dose of corticosteroids is one which removes acute pain and tenderness within 48 hours. NB in nerves that are chronically thickened and fibrosed it may not be possible to reduce all that the patient calls pain with corticosteroids. He may have a permanent discomfort he must learn to live with that. HOWEVER IT HAS BEEN OBSERVED THAT WHEN STEROIDS ARE BEING GIVEN TO THE PATIENT THE BODIES ABILITY TO ELIMINATE THE LEPROSY BACILLUS IS REDUCED AND SO IT IS RECOMMENDED THAT IN ESTIMATING THE DURATION OF THE MDT THE TIME ON STEROIDS IS NOT INCLUDED IN THE 12 MONTHS THAT WHO RECOMMENDS. TYPE 2 REACTION. MILD. Mild ENL is of nuisance value only. But it warns that antibody is present and the patient is sensitised. The best management is to increase the Lamprene to 100 mg daily (200-300 mg daily is more severe cases). Lamprene requires 6-8 weeks to exert its maximum anti-inflammatory effect. So during this time also give:

AGW\Reactions\2006

11

Aspirin 500mgms x 3-4 daily or Paracetamol 1gm x 3-4 /day. Largactil 50mgms nocte. Adequate vitamins and diet. Investigate for other medical conditions that may complicate the picture. WE DO NOT AIM TO REMOVE ALL ENL- WE AIM TO KEEP THE PATIENT COMFORTABLE AND FREE OF ULCERATION, AND ON ANTILEPROSY THERAPY. More severe ENL is best checked in Hospital before further medication. ADMIT. Ensure adequate fluid intake (esp in summer patient may be dehydrated- ideally urine ought to be measured so that there is an output on 2 litres daily to make sure!) and balanced diet. Give anti-inflammatory and sedative as above., Increase Lamprene to 100-200-300 daily depending of severity of reaction and patients size. Ensure no constipation. Do full blood check and urine check, and intestinal parasites.. Eliminate other intercurrent infections and diabetes. DO NOT GIVE STEROIDS THE FIRST DAY- GET A PROPER PICTURE OF PATIENTS CONDITION, AND DIURNAL TEMPERATURE VARIATIONS . If worry is a big factor give more tranquillisers even up to Largactil 100mgms x 4 per day in a big man. If ENL is due to vaccinations, flue etc that are transient it will settle in a week or so without any more specific therapy. If Hb is low give transfusion plus haematinics. In short give the patient physical and mental rest and eliminate other medical problems. If the patient settles down he can go home on same regimen and the medication is slowly reduced, reducing only one medication partly each visit. DO not give steroids when first seen, they should not be used unless really necessary, they mask the problem, they do not solve the problem. Some Type 2 reactions respond well to chloroquine 300mg base at night. (plus the above). Some do well with antimonials (Sodium antimony Tartrate) Some do well on phenobarb 30mg x4/d THALIDOMIDE is considered an excellent anti-ENL drug. Remember it also has toxic (teratogenic) effects and should only be given for home use if the patient is completely trustworthy and not to women of child bearing age. Dose should be 4-500mg daily to commence. Usually start with 100mg in am and noon and 200mg nocte. A severe problem may need 200 morning and nocte and 100 at noon. Within 3-4 days the staff ought to be able to see improvement and the patient feel better. Then drop to 100mg x 3 daily. The dose can be dropped by 100mg each week in mild cases- or cases of acute onset. But if it can be withdrawn so quickly one wonders if there was need for using it anyhow. Severe ENL may need a dose of 200mg daily for several months, perhaps 100 mg nocte for 6-9 months and perhaps 100mg nocte for even a year. This is especially so in patients with poor socioeconomic situations or unstable personalities. There is no need to give Aspirin while on adequate Thalidomide but it is often introduced during withdrawal to decrease the duration that the Thalidomide is needed. Please make sure that blood and other medical problems are adequately treated while on Thalidomide. Otherwise once the thalidomide is withdrawn the ENL will return! Corticosteroids are the other mainstay in the treatment of Type 2 reaction. Yes they appear very effective BUT the patient who receives corticosteroids is probably curing himself more slowly than he would without them. Unfortunately Corticosteroids do not cure the reaction they only suppress it and when the steroids are stopped it may return. Hence the need to correctly diagnose any causal problem and treat it adequately while on steroids so there is less chance of ENL recurring

AGW\Reactions\2006

12

when the steroids are stopped. PLEASE NEVER GIVE STEROIDS LONG TERM IN ANY ENL PATIENT WITHOUT COMPLETE EXAMINATION AND RECORDING OF ALL FINDINGS AND COMPLETION OF INVESTIGATIONS FOR CAUSES. Steroids mask other diseases and so make them difficult to identify. Corticosteroids make the patient feel better quickly and the patient thinks he is being well treated and the doctor feels good about his results, BUT THINK LONG TERM you MUST FIND THE CAUSE OF WHY THE ENL IS SEVERE, OR YOU MAY NEVER WEAN THE PATIENT OFF STEROIDS IF THAT HAPPENS YOU ARE VIRTUALLY SIGING THE PATIENTS DEATH WARRANT. And beware steroids can be bought over he counter here and patients think that the steroids are doing them good and so buy for themselves and may end up doing themselves a lot of harm. I have seen a number of deaths caused in this way. Prednisolone is the steroid of choice in ENL, it has a relatively short half life and if given before 9am will be excreted before the next stimulus determines how much steroid the patient secretes the next day. Hence is less likely to depress the adrenals than if it is given in divided doses or if dexamethasone is used. Most patients will do well on 30-40mg daily, unless they have had a lot of steroid previously. One will observe that the pain and tenderness go within 48 hours and the fever should fall within 24 hours. It should not be necessary to use 30-40mg for longer than 1 week initially. Our regular routine is 30mg daily to start and each week the patient takes 1 tablet (5mg) less each day. So to start with 30mg gives a 6 week course. If the reaction promises to be more severe the patient can be kept on 10-15 or even 20mg for longer than the week, It is usually best to see each week (or two at the most) till one determines what is the minimum needed to keep the reaction controlled. Steroid is anti-inflammatory and acts in that capacity quickly. Any patient admitted with severe ENL for whom it is considered that steroids are needed should be started as soon as possible on clofazimine 300mg daily. It will darken the skin but it is anti-inflammatory action slowly builds up so that by the time the 6 week course of steroids is completed the clofazimine ought to be exerting an anti-inflammatory effect to substitute for the steroids. After 3 months if the reaction is controlled the clofazimine can be slowly reduced. It is very easy for a patient to become dependant on steroids, especially if they have untreated medical problems. If this happens the best method of dealing with the problem is to titrate the steroid to find the dose just needed to control the ENL. Then add thalidomide as above 400mg daily to start and then after one week 300mg daily. Hold the thalidomide level at 300mg while the steroid is reduced. It is usually possible to reduce only 5mg each week or two, so it means a long time on Thalidomide. Once the patient is free of steroids the thalidomide is slowly tapered off. It is recommended that thalidomide never be given to women of childbearing years. In cases of steroid dependence there is no other real method of weaning them so they should be put on an injectable contraceptive or IUD for at least a month before the thalidomide is started. It is still important they know the dangers of the drug and not to share it with others if it is given at home. Many hospitals will not give any thalidomide to a patient to whom every dose cannot be given under supervision. FROM PERSONAL EXPERIENCE I HAVE FOUND THAT THE MAJORITY OF TYPE 2 LEPRA REACTION PATIENTS CAN BE MANAGED WITHOUT STEROIDS OR THALIDOMIDE IF ADEQUATE REST, TRANQUILLISERS AND CLOFAZIMINE IS GIVEN. Also if a thorough search is made to find the cause of the reaction, thorough workup and elimination of any other disease or socio-economic problem. THERE IS OBVIOUSLY A BIG FACTOR IN DOCTOR - PATIENT RELATIONSHIP AND THE CONVICTION THAT THE DOCTOR IMPARTS TO THE PATIENT WHEN HE "SELLS" THE IDEA OF CLOFAZIMINE TO THE PATIENT. Yes, clofazimine can have some gastrointestinal side effects, but they are relatively uncommon and less likely to occur if the patient takes the capsules with a greasy meal. Initially (1966-8) we used to give a teaspoon full of

AGW\Reactions\2006

13

peanut oil with every dose as the drug is oil soluble. This was later deemed un-necessary but is useful in those who do complain of gastric disturbance after taking it with meals. Zinc Sulphate has long been recommended as a supplement for all patients with ulceration for over 6 weeks. In them the blood Zinc levels fall. It has also been found that Zinc Sulphate, which is essential for enzyme activity and some immune mediators, will assist in the control of ENL and steroid or thalidomide withdrawal. We use 220mg daily in one dose. There are many other drugs and treatments that have been used as supplements in Reaction therapy. Personally we found the addition of Calcium reduced the severity of leprosy reaction and nerve discomfort, but this is one of those things that would be almost impossible to prove. Any patient with chronic reaction needs careful counselling and medical help, and encouragement in the times he is down and feels nothing is going right. Unfortunately steroids do give a feeling of euphoria and it may become difficult to stop steroids once the patient has become used to them, without substituting some other drug. In Hong Kong we usually used Largactil for steroid withdrawal as we did not have thalidomide. Yes It did work, it was slow, but we got there, and I still use it in many countries. Reactions are among the most difficult complications of leprosy. I have not dealt with the management of iritis in this paper. It is just one of the complications that need specialist care. However it must be looked for in any patient with ENL or type 2 reaction. It also should be checked for in any patient with loss of eyebrows. Find iritis early, and treat it correctly, and you can save sight. If in doubt treat any LL patient with chronic ENL, (especially if on steroids or thalidomide) with nightly drops of atropine or at least homatropine so that the iritis in which ENL occur rapidly does not become adherent to the lens. Hands and feet in acute reaction need daily physiotherapy to prevent the development of deformities. Prevention is relatively easy. Correction of deformity is not. Even if paralysis has occurred daily exercise maintain mobility and the correct exercises given early can en courage return of function. Foot drop should always have a correcting spring, better than an AFO.

LML - send your messages to: Dr Salvatore Noto Padiglione Dermatologia Sociale Az. Ospedaliera Universitaria S. Martino Largo R. Benzi, 10 16132 Genoa, Italy

AGW\Reactions\2006Tel: (+39) 010 555 27 83 - Fax: (+39) 010 555 66 41 - E-mail: [email protected] LML Archives: http://www.aifo.it/english/resources/online/lml-archives/index.htm

14