ENL or relapse in a BL/LL patient?

Leprosy Mailing List – May 3^rd, 2012

Ref.:   ENL or relapse in a BL/LL patient?
From: G Warren, Sydney, Australia

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Dear Salvatore,

I refer to the letter from Dr Kawuma in Uganda (LML May 3^rd, 2012).

Yes, definitely down grading reaction can occur and it frequently did in the “old days” when a patient was receiving one drug only, when the patient developed resistance to that drug.  In the 1960s it was usually dapsone but, also downgrading reaction occurred to some of the other drugs in which initial improvement had appeared to occur and then the patients would down grade till we changed the antileprosy drug therapy.  It usually required several years for such resistance to show up.

It also occurred in patients who had been given multidrug therapy because they were not responding to dapsone and so were considered dapsone resistant; though there was no ability to test for resistance to dapsone.  After a period often a year or two the disease seemed under control and the patient stopped drug therapy (often just by dropping out himself but sometimes by completing the 12 months recommended for MDT).  But after several years the patient would reappear with what was said to be ENL; but on careful testing one would find the bacteriological index (BI) was higher than it had been at the last test.

It is fascinating how one can separate between new lesions of downgrading BL/LL and the lesions of ENL that look similar.  Restarting adequate anti-leprosy medication especially including the use of clofazamine, seemed to rapidly deal with the problem that was apparently resistance to dapsone and the multidrug therapy had not been given long enough.

I hope that will help.  When a patient returns with what is queried to be ENL or relapse in a BL/LL patient who has completed the recommended 12 months MDT it is wise to check the lesions for infiltration, by pressing a glass slide onto the lesions.  The pressure of a slide will define the edge of the lesion.  If it is ENL there will be a well localised small patch of infiltration but, if it is a new lesion ie true relapse, it will not be so definite and not so erythematous.

We need to be on the watch for such relapses!

Grace Warren

Previously Superintendent Hong Kong Leprosarium 1960-1975.

Ungrading and downgrading reactions; do these concepts help us?

Leprosy Mailing List – May 3^rd, 2012

Ref.:   Ungrading and downgrading reactions; do these concepts help us?
From: J A da Costa Nery, Rio de Janeiro, Brazil

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Dear Salvatore,

It´s always a pleasure to follow these reports, so we can think upon them.  In my whole life studying leprosy, these nomenclatures [upgrading and downgrading reactions] always bothered me.  I find them, as a clinician, very hard to distinguish on a daily basis.

I don’t really know if these concepts help us in the programme and, not all doctors know how to use that kind of nomenclature while treating reactional episodes.  The discussion on appearance of either upgrading or downgrading type 1 reaction [type 1 reaction is also commonly referred to as reversal reaction or RR] is very relevant to the knowledge on leprosy in the state of art.  Nevertheless, such a goal is more likely to be achieved by basic researchers, by means of immunologic tests; not by clinicians.  Moreover, it is not always possible, given that cellular proliferation and activation tests are not deemed as a golden standard assessment.  On the other hand, histopathology is also helpful for the definition of RR, although such examination is not very useful to evaluate the characteristic of such a reaction (either upgrading or downgrading). 

It’s always good to hear new opinions so we can discuss.  Lately I´ve been studying cases of relapse in leprosy, and I´ll watch out for these type 1 reactions, which are treated with long term corticosteroids,  can they be included in the downgrade?

We have a large experience with a number of RR cases per year, and our most relevant concern relates to the long-term use of corticosteroids and risk of disability. 

Best wishes,

Dr. José Augusto da Costa Nery
Fiocruz 

What would be the meaning of the downgrading type 1 reaction in terms of the management of the patient?

Leprosy Mailing List – May 1^st, 2012

Ref.:   What would be the meaning of the downgrading type 1 reaction in terms of the management of the patient?
From: H K Kar, New Delhi, India

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Dear Dr C Shumin,

Thanks for your message [LML April 23rd, 2012].  The term downgrading type 1 reaction is basically downgrading of the spectrum of the disease with some amount of inflammation over some of the lesions.  In those cases simply multi-drug therapy (MDT) has to be started immediately.  These patients need close watch, since they are likely to develop upgrading type 1 reaction.

Regards

Dr (Prof.) H K Kar
Dean, PGIMER, Dr R M L Hospital
Consultant & HOD
Department of Dermatology, STD & Leprosy
P.G.I.M.E.R. and Dr Ram Manohar Lohia Hospital
Baba Kharag Singh Marg
New Delhi-110001

Neuritis, acute and chronic, in leprosy

Leprosy Mailing List – February 28^th, 2012 

Ref.:    Neuritis, acute and chronic, in leprosy

From:  H Srinivasan, Chennai, India

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Dear Dr Noto,

The following are my views regarding the queries raised about "Acute neuritis" in leprosy.  I think it will help starting from the definition of neuritis and then considering acute and chronic neuritis.  I also report some relevant aspects of histopathology.

Definition of leprosy neuritis

Leprosy neuritis is an inflammatory mononeuropathy occurring in leprosy.  In can be acute or chronic.

Acute leprosy neuritis 

Acute leprosy neuritis describes the clinical state characterized by pain occurring in an obviously thickened peripheral nerve trunk such as ulnar, median, lateral popliteal nerve etc.  It may occur in cutaneous nerve trunks also, but here there is no risk of disability and deformity, although the condition may be quite distressing to the patient.  Acute neuritis is of rapid (i.e., acute) onset, over the course of a few hours to a few days.  It may have been present for a few days to a few weeks by the time the patient is seen by the physician or paramedical worker.

It may be moderately severe or severe.  In moderately severe acute leprosy neuritis patient complains of severe pain, but the movement of adjacent joint is not restricted and sleep is not disturbed because of pain.  In severe acute leprosy neuritis patient complains of severe pain and the movement of adjacent joint is restricted due to the pain and patient admits that pain disturbs sleep. 

Often, acute neuritis occurs in a background of chronic neuritis.  Acute neuritis may occur along with cutaneous manifestations of type I or type II reaction, or as an isolated clinical manifestation of the reactional process.

The term “acute leprosy neuritis" when used in the histopathological context indicates presence of foci of polymorpho nuclear leucocyte infiltration in the nerve (micro or macro “hot abscess”).

Chronic leprosy neuritis

 “Chronic leprosy neuritis” is the clinical condition where there has been long standing ‘mild’ (patient admits to having pain in the nerve only on asking about it) to ‘moderate’ nerve pain (complains of pain even without asking about it, but says it is not severe) in one or more peripheral nerve trunks of the limb(s).   

Histologically, every case of leprosy shows some evidence of chronic neuritis at some site in the peripheral nervous system.  Leprosy is not diagnosed without such evidence.   

Clinical examination

On examination, the concerned nerve trunk is obviously thickened (swollen), and very tender (very painful on palpation), such that the patient is afraid of palpation of the nerve.  Range of active movement of the adjacent joint is restricted because of pain; and/or passively increasing the range aggravates pain in the nerve.  There may be clinical nerve function deficit relating to the affected nerve trunk, which may be pre-existing or of recent origin along with the attack of acute neuritis or, pre-existing nerve function deficit may have worsened coincident with the attack of acute neuritis or, there may not be any clinically identifiable nerve function deficit.  

Indications for Steroid therapy

Onset or worsening of clinical nerve function deficit relating to the affected nerve trunk (eg., sensory loss, muscle weakness or paralysis) along with acute neuritis or even while the condition is under treatment with other drugs is an absolute indication for immediate institution of steroid therapy in adequate dosage.  Continued severe nerve pain even in the absence of increasing nerve function deficit or in a destroyed nerve trunk (with no possibility of the nerve recovering) despite adequate analgesic therapy is often relieved by steroid therapy.

Nerve conduction studies

One does not wait for or depend on nerve conduction studies for diagnosing and treating acute neuritis.  They may be used, when available, for monitoring efficacy of therapy.  Nerve conduction velocity (NCVs) may be within normal limits when only slow conducting fibres are damaged.  Marginal improvement in NCVs without clinical improvement is of no material benefit to the patient.

Early detection of leprosy neuritis

Patient is the best person to suspect early the possibility of acute neuritis and report for treatment without delay.  So the patient should be trained to look for and suspect acute neuritis as well as onset/worsening of nerve function deficit of his or her thickened nerve trunks.  The paramedical and medical personnel must be sensitized to show concern and examine the patient very carefully and sympathetically when a patient reports for suspected acute neuritis and not play down or neglect the patient.  It goes without saying that they must know how to examine such patients.

H Srinivasan, FRCS
Surgeon (Retd)
25 First Seaward Road
Chennai - 600 041
INDIA

Proposal for "Guidelines for the management of acute neuritis in leprosy” – Part I. Definition, clinical signs and electrophysiology

Leprosy Mailing List – February 14^th, 2012 

Ref.:    Proposal for "Guidelines for the management of acute neuritis in leprosy” – Part I. Definition, clinical signs and electrophysiology

From:  B Naafs, Munnekeburen;  P A M Schreuder, Maastricht, The Netherlands

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Dear Salvatore,

Very much, “thank you” to Dr Antoine Mahé (LML January 18^th, 2012) and to colleagues contributing to the topic about “acute leprosy neuritis”.  It is difficult to answer all Dr Mahé’s questions because one is always subjective!  Herewith are our answers:-

1) What is your definition of 'acute leprosy neuritis’?

<< Definition of acute neuritis:-  Acute neuritis in leprosy is the occurrence within a few days of increase in pain, or tenderness, decrease in voluntary muscle test (VMT) and sensory testing (ST) scores, severely diminished motor nerve conduction or nerve block in peripheral nerves serving the eye lids, face, hands and feet.  Since patients are not seen every day, “acute” goes up to 3 months.  >>

2) Which are the clinical symptoms and signs to be taken into account for justifying the implementation of a specific therapy of acute neuritis (i.e., systemic steroids):

<<. >>

2a Presence of pain: spontaneous? Provoked by palpation?  Or by movement?

<< All of them are important and justify therapy but, especially tenderness at palpation. >>

2b Recent occurrence of neurological dysfunction (sensory, motor, autonomic)?

<< All of them are important but, most decrease in VMT and ST scores, because these are easy to measure. >>

2c Definition of "recent"?  With or without pain?

<< We would consider “recent” when within 3 months. >>

 3) Relevance of electromyography and nerve conduction studies?

<< Nerve conduction studies are relevant but, they are not widely available. >>

4) Strategies for early detection of incipient neuritis during follow-up of known patients?

<< Periodical assessment of the patient by a combination of: - always look, palpate, compare and test.  Look at the face and eyes: do the eyes blink?  Any degree of lagophthalmos?  Any deviation of the mouth?  Look at hands and feet:- any dryness, atrophy or wounds?  Palpate* the peripheral nerves of predilection of leprosy.  Comparealways the two sides.  Test by performing the voluntary muscle test and sensory test on eyes, hands and feet.

We hope these answers help. 

Best regards,

Ben Naafs and Pieter Schreuder

* Description of the palpation of the peripheral nerves of predilection of leprosy is available on line at: - The Diagnosis of Leprosy – text and slides <<http://atlasofleprosy.hsanmartino.it/ >>

Proposal for "Guidelines for the management of acute neuritis in leprosy” – Part I. Definition, clinical signs and electrophysiology

Leprosy Mailing List – February 11^th, 2012 

Ref.:    Proposal for "Guidelines for the management of acute neuritis in leprosy” – Part I. Definition, clinical signs and electrophysiology

From:  L Reni, Genoa, Italy

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Dear Salvatore,

Thank you very much to Dr Antoine Mahé for introducing such an important topic (LML January 18^th, 2012).  Herewith are my answers:-

1) What is your definition of 'acute leprosy neuritis' ?

<< "Acute leprosy neuritis", my definition:-

It is an acute inflammatory mononeuropathy presenting with pain spreading, from a point of entrapment (for example at the ulnar groove or in the cubital tunnel), along the nerve.

There is tenderness and/or swelling of the nerve; its palpation evokes a typical “electric shock” along the nerve with paraesthesia in the area of its cutaneous distribution (Tinel's sign).

The pain may be isolated or accompanied by neurological dysfunctions (sensitive and/or motor and/or autonomic).  The neuritis may be considered acute if symptomatology and/or signs have arisen within a few weeks.  >>

2) Which are the clinical symptoms and signs to be taken into account for justifying the implementation of a specific therapy of acute neuritis (i.e., systemic steroids):

<< The implementation of a specific therapy is necessary whenever a peripheral nerve lesion is suspected. >>

 2a Presence of pain: spontaneous? Provoked by palpation?  Or by movement?

<< The pain may be absent.  If present, it may be spontaneous, provoked by palpation or by movement. >>

2b Recent occurrence of neurological dysfunction (sensory, motor, autonomic)?

<< Neurologic dysfunction may be sensory (sensory deficit or paraesthesia) and/or motor and/or autonomic. >>

 2c Definition of "recent"?  With or without pain?

<< "Recent" means within a few weeks.  Pain may be absent. >>

3) Relevance of electromyography and nerve conduction studies?

<< Electromyography is useless.  Nerve conduction studies are useful; it allows the diagnosis in dubious cases, detecting the nervous lesion, while waiting echography and surgical approach.  Nerve conduction has proved to be useful in our experience demonstrating focal modifications in quite modest or dubious cases and previous to the appearance of clinical symptoms. >>

4) Strategies for early detection of incipient neuritis during follow-up of known patients?

<< The patient needs instructions about the possible symptoms leading to a dramatic evolution.  Sensory testing and voluntary muscle test are performed periodically.  Nerve conduction study is useful. >>

Best regards,

Lizia

Dr Lizia Reni

Department of Neurology

University of Genoa,

Genoa, Italy

Proposal for "Guidelines for the management of acute neuritis in leprosy” – Part I. Definition

Leprosy Mailing List – February 2^nd, 2012 

Ref.:    Proposal for "Guidelines for the management of acute neuritis in leprosy” – Part I. Definition

From:  H K Kar, New Delhi, India

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Dear Dr Noto,

Thank you very much to Dr Mahé and to the Association of the French speaking leprologists for this initiative (LML 18^th Jan. 2012).  Herewith I am trying to give my opinion on the first question:

1) What is your definition of 'acute leprosy neuritis' ?

My definition:-

<< Sudden onset of acute inflammation of the nerve presenting with acute pain in peripheral nerve or nerve tenderness and/or swelling due to nerve abscess with or without recent onset of neurological deficit of usually 6 months duration in a leprosy patient is called as “acute leprosy neuritis”.

Best regards,

Dr (Prof.) H K Kar
Consultant & HOD
Department of Dermatology, STD & Leprosy
P.G.I.M.E.R. and Dr Ram Manohar Lohia Hospital
Baba Kharag Singh Marg
New Delhi-110001

Proposal for "Guidelines for the management of acute neuritis in leprosy” - Definition, symptoms and signs

Leprosy Mailing List – January 18^th, 2012 

Ref.:    Proposal for "Guidelines for the management of acute neuritis in leprosy”

            Definition, symptoms and signs

From:  A Mahé, Paris, France

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Dear Dr Noto,

With the ongoing transfer of the leprosy control activities to the general health services, the Bulletin of the French-speaking leprologists (BALLF) aims at providing to health personnel clear and understandable outlines of some of the conditions related to leprosy they may encounter.  The diffusion of the Bulletin is covering francophone Africa, South East Asia and the Caribbean area. Proposals of all LML affiliates are welcome.

Therefore, we would like to propose in our journal standardized "Guidelines for the management of acute neuritis in leprosy".  In that perspective, and owing to the relatively high variability of practices in that specific field, it seemed to us interesting to question the affiliates of the leprosy mailing list about their practices in their institutions.

We would be very grateful for those who would let us know those practices.  A synthesis will then be performed, and communicated to the leprosy mailing list.

We have selected the following questions about definition, clinical signs and electromyography (Part I.);

1) What is your definition of 'acute leprosy neuritis' ?

 2) Which are the clinical symptoms and signs to be taken into account for justifying the implementation of a specific therapy of acute neuritis (i.e., systemic steroids):

2a - presence of pain : spontaneous ? Provoked by palpation ? Or by movement ?

2b - recent occurrence of neurological dysfunction (sensory, motor, autonomic) ?

2c Definition of "recent" ? With or without pain ?

3) Relevance of electromyography and nerve conduction studies ?

4) Strategies for early detection of incipient neuritis during follow-up of known patients ?

Thank you so much for your answers and comments,

Dr Antoine Mahé

Editor of the Bulletin of the French-speaking leprologists (BALLF)

Dr Antoine Mahé

Dermatologie

Hôpital Pasteur

39, avenue de la Liberté

68024 Colmar Cedex

Secrétariat (+33) 03 89 12 44 65 / 41 58

Fax (+33) 03 89 12 47 69

Portable (+33) 06 31 27 68 71

NB Part II Medical and surgical therapy will follow.

Request of address of Doctor with experience in leprosy in Cuba

Leprosy Mailing List – December 15^th, 2011

Ref.:   Request of address of Doctor with experience in leprosy in Cuba

From: S. Noto, Genoa, Italy

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Dear All,

We have here in Genoa a patient of leprosy that has been treated for ENL reaction.  He is going back home to “Jsla del la Juventud”, Cuba.  I am looking for the address or contact numbers of a Doctor with experience in leprosy in Cuba to whom referring the patient.

Thank you very much in advance,

Best regards,

S. Noto

What is in paucibacillary (PB) leprosy?

Leprosy Mailing List – November 12th, 2011

Ref.:   What is in paucibacillary (PB) leprosy? From: J Barreto, Bauru, S. Paulo, Brazil

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Dear Dr Noto,

Thank you very much to my friend Dr Ben Naafs, and also to Dr Pieter Schreuder for their comments (please see LML 9^th Sept., 2011).

1. Yes, there is a spectrum in leprosy classification, and low resistant tuberculoid is a fact, even though I have seen only less than 10 cases in more than 10 years, and in more than 15.000 slides of leprosy cases which I saw during 8 years as dermatopathologist at the Instituto Lauro de Souza Lima (ILSL).

2. According to 1971 Ridley’s Classification (Five from seven groups), there is a group called TI (Indefinite Tuberculoid), who develops type 1 reaction, but this group is not the same of tuberculoid reactional described by Wade and Lauro de Souza Lima in the beginning of the 20 century.  The name reactional tuberculoid leprosy, grouped later with BT patients in R&J Classification 1962/1966, should be deserved to patients with usually a lesion clinically and histopathologically indeterminate (early), whose developed, in most cases, a reaction in the first or second month of therapy, usually with few or no nerve symptoms, and the normal evolution was to cure.  These patients had a Mitsuda reaction of 2+, i.e., 6 to 10mm diameter, different from TT patients (>10mm or ulcerated).  Ridley, in his paper "Skin biopsy on Leprosy", 1987, second edition, pointed that TI is not the same as TR, though both undergone reactions.  At the ILSL we recognize 2 groups of low resistant tuberculoids: "T in reaction", which in turn are really BT patients, i.e., annular tuberculoid lesions with satellite lesions and erythema after the beginning of treatment, and "reactional tuberculoid", described above.

3. It is also important to know that is very difficult to distinguish, even histopathologically, true TT from BT cases.  Dr Fleury published a paper about this, in Hansenologia Internationalis.  Ridley (1974) pointed some clues, as the lower destruction of epidermis and dermal nerve branches, as well as the presence of more Langhans giant cells in granuloma, but the main clue is the bacilloscopy (slit-skin smear examination), and sometimes only the evolution over long term follow up.

4. About bacilloscopy, as many as 90% of smears are made with bad quality in Brazil, and I believe that few technicians in the world, as well, are able to perform it correctly.  I performed a study in 2010, in the state of Mato Grosso do Sul, Brazil, that I am going to present on the next International Leprosy Congress in Brazil.  Why I made a study in this state? Because the quality of smears, on indirect evaluation, was said more than 99% good, and for this reason, it was the model for the country.  Nevertheless, when we went to the field, and on direct evaluation, less than 10% of the smears were made in good conditions, i.e. good collection, fixation, staining and reading.  This is the likely reason which explains why patients with less than 5 lesions are said PB: the smear collection from the lesions needs a good technics, and usually it is not possible to make it with tools other than the fingers, and for this reason almost all technicians DO NOT COLLECT from lesions.  This is a fact.  Once in cases of initial borderline leprosy the bacilli are found only in lesions, of course, index points will show no bacilli, and patients will be considered wrongly PB.

5. How long must we wait to say the patient is healed?  5yrs?  10yrs?  How many long term follow up of PB patients, with good methodology, are described on literature?  On my recent review of literature for my PhD thesis, ALL of them had less than 10yrs, and ALL the relapsed cases in these studies were diagnosed only by spontaneous demand.  If we wonder that M. leprae can stay dormant in Schwann cells as many as 10yrs, and duplication time is almost 2 weeks, how many time must we wait to find and show viable bacilli on skin biopsies, or even on smears (which have lower accuracy), in order to distinguish between reversal reaction and relapse, after a short course of treatment in a borderline patient?

6. Finally, if, in a normal distribution of cases in the spectrum, only 10% have Mitsuda reaction positive (Ridley, 1974), and only these patients are able to destroy dormant bacilli inside nerve fibers, once metabolic inactive M. leprae will not be destroyed by MDT, what will be the real percentage of good prognosis MDT PB treated patients?

These are only some questions, which I still do not have answers.

Regards,

Jaison

Acute abdomen in lepromatous (LL) leprosy

Leprosy Mailing List – November 3^rd, 2011

Ref.:   Acute abdomen in lepromatous (LL) leprosy.
From: Barreto J, Bauru, S. Paulo, Brazil

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Dear Salvatore, 

The questions that must be made about this case:

1. Is this patient with active (non treated) lepromatous leprosy?  If the answer is yes, Lucio's fenomenon must be ruled out; once it is not uncommom deep vascular trombosis in this type of leprosy.

2. Is this patient in erythema nodosum leprosum (ENL or type 2) reaction?  As well as in Lucio's fenomenon, deep trombosis also can occur during this reaction.  Dr Opromolla and Dr Raul Fleury published cases of deep vascular trombosis during type 2 reaction, in the past, in Hansenologia Internationalis (www.ilsl.br).  Some cases developed even myocardial infarction.

If the answer to both questions is no, other causes must be involved.

Regards,

Jaison 

“We changed and gave the clofazimine with a meal”

Leprosy Mailing List – November 3^rd, 2011 

Ref.:   “We changed and gave the clofazimine with a meal”.

From: G Warren, Sydney, Australia

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Dear Dr Noto,

Thank you for publishing that letter and picture by Dr Peton.  He does not mention what antileprosy medication the patient was on. -  was it multi-drug therapy (MDT)?  Was the patient on clofazimine – at what dose and for how long?

My comments are that in the early days we often used to use clofazimine as monotherapy (when doing the initial drug trials) and we used to give a dose of oil with each dose as initially recommended.  But we often gave it in 200 or 300m mgms daily.  Yes, it did produce a very dark skin in the Chinese patients.  A few of the patients did complain of abdominal discomfort if they did not take the oil. 

One patient was actually admitted to the major govt hospital and operated on for a suspected abdominal problem as he complained of persistent gastric discomfort.  From Memory (this was about 1970) they found very heavy pigmentation with clofazimine in the mucosa of the ileum and colon which were apparently very dark in colour (No I did not see it nor do I have a photo- good on you for getting the record).  But no evidence of gastric ulceration or other regular cause of gastric discomfort.  From that incident we changed and gave the clofazimine with a meal and had no further similar complaints.

Sometime in the 1980s an article appeared stating that clofazimine caused diarrhoea and similar problems but the case written up also had amoebic dysentery!  No we (treating literally hundreds of patients and doing regular path testing) found that clofazimine causes very few if any complications other than the discolouration of skin that fades within about a year of discontinuation.  But we did find that many of the biochemical abnormalities present (eg poor liver and kidney function) initially were corrected within the first year.- oh yes we treated any obvious abnormalities such as anaemia and parasites! 

I am sorry I cannot quote the publications concerned now-  but would be interested as to the symptoms of the patient he speaks about and recommend the clofazimine be given with his meals and or oil, in future.

Yours sincerely,

Grace Warren

Previously superintendent Hong Kong leprosarium 1960-75 and

Adviser for The Leprosy Mission In Asia for 1975-1994.

Unnecessary laparotomy for abdominal pain and fever due to clofazimine

Leprosy Mailing List – November 3^rd, 2011 

Ref.:   Unnecessary laparotomy for abdominal pain and fever due to clofazimine

From: Bryceson A, London, UK

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Dear Salvatore

I wonder if the patient was taking clofazimine.  If so, the red coloration might be due to clofazimine.  Clofazimine can cause abdominal pain, sometimes mimicking an acute abdomen.  The pain is thought to be due to an inflammatory reaction to crystals of the drug deposited in the small bowel mucosa and mesenteric lymph nodes.  For this reason the high starting dose (300 mg) of clofazimine that is used to control ENL (Type 2) reactions, should be reduced after 2 or 3 weeks.  References go back a long way, but here are some recent ones.

Jadhav MV, Sathe AG, Deore SS, et al. Tissue concentration, systemic distribution and toxicity of clofazimine--an autopsy study. Indian J Pathol Microbiol. 2004;47:281-283.

Mathew BS, Pulimood AB, Prasanna CG, et al. Clofazimine induced enteropathy--a case highlighting the importance of drug induced disease in differential diagnosis. Trop Gastroenterol. 2006;27:87-88.

Sukpanichnant S, Hargrove NS, Kachintorn U, et al. Clofazimine-induced crystal-storing histiocytosis producing chronic abdominal pain in a leprosy patient. Am J Surg Pathol. 2000;24:129-135.

I made the same mistake in 1979

Bryceson A. Unnecessary laparotomy for abdominal pain and fever due to clofazimine.  Lepr Rev. 1979 Sep;50(3):258-9.

Best wishes,

Anthony Bryceson

Abdominal complication of clofazimine

Leprosy Mailing List – November 3^rd, 2011 

Ref.:   Abdominal complication of clofazimine

From: W S C Smith, Aberdeen, UK

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Dear Dr Peton,

Thank you for circulating this photograph.  Had the patient been taking clofazimine – if so at what dose and for how long?

There are a few case reports in the literature of acute abdomen/abdominal pain associated with crystal formation due to clofazimine – I have attached reports from India, Thailand and Singapore – there are probably a few more.

Cairns Smith

http://informahealthcare.com/doi/abs/10.3109/00313029309068897

“PB-ish” leprosy in the paler skins

Leprosy Mailing List – November 2^nd, 2011 

Ref.:   “PB-ish” leprosy in the paler skins

From:  G  Warren, Sydney, Australia

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Dear Dr Noto.,

Thank you very much for circulating the TEXT and SLIDES of “The Diagnosis of Leprosy”.  Of course, last year, when the original version was produces I was carefully following and participating the discussions together with you, Drs Schreuder and Naafs.  With pleasure, I also offered some contributions, to help the newer workers to learn the tricks we have learnt, by often bitter experience, over many years. -

There seemed to be a number of letters in the week ending 16^th October and some excellent pictures on dark skin.  However, last weekend I wrote to you a letter that some how seems to have slipped through  the cracks, that I think would help especially those workers faced with the PB-ish [paucibacillary] leprosy in the paler skins but, I have seen no evidence of it so, I send again (after this note) in the hope that you will be able to circulate it.  I feel it makes some important points about the diagnosis and management of PB-ish leprosy

Sunday 16^th October.

Dear Dr Noto,

Thank you for publishing Dr Barreto’s letter [LML Oct. 15th, 2011 “What is paucibacillary (PB) leprosy?”].  I have seen many patients who were initially treated as paucibacillary leprosy according to the WHO guidelines who have returned 3-10 years later with obviously mid borderline/borderline lepromatous (BB/BL) type lesions.  On careful history taking one can realise that initially the patients was never properly classified.  According to WHO the PB leprosy is less than 5 lesions, but in their guide book there is no other specific requirement.  PB implies few bacilli and in true tuberculoid (TT) leprosy the lesions are usually well defined and on one area of the body implying that the bacilli are not wide spread.  However bacilli can well be in nerves in other parts of the body and they do not produce skin lesions.  As Dr Barreto implies patients may well be multibacillary (MB) with marked neural leprosy but very few skin lesions.

In Teaching in Asia I used to stipulate that to be treated as PB the patients’ lesions must be all in one area of the body; this unfortunately, is not  according to WHO classification.  We often had no possibility of doing a slit-skin smear examination and so deemed it preferable to give the MB treatment and prevent “relapses”.  In the last 10 years I have treated a number of immigrants to Australia who have previously been treated in an endemic country for PB leprosy and have represented 3-7 years later, in Australia, with definite BB-ish leprosy!  One almost pure lepromatous (LL) type of disease and the lesions were hardly visible even on the relapse.  Yes I call it relapse not reinfection.

As Dr Barreto states the bacilli live in the nerves, and may be in very high concentration in the nerves while there are few in the skin, and it has been shown that the bacilli can survive, for many years, in the nerves  in spite of heavy doses of rifampicin, and can emerge later, still fully sensitive to rifampicin, to  continue the Infection.  So, I would plead with clinicians if there is any possibility of having less that excellent natural resistance, that the patient be given MB treatment rather than PB.  

Also treat intercurrent medical conditions that could reduce the patient ability to deal with the leprosy infection.  Also do not just brush aside the possibility of relapse.  It turns up more frequently than appears in the statistics because there is now no continuous registrar and as Dr Rao states (in LML 15^th Oct)  it is difficult to convince the authorities that a patient has a relapse when he represents with new lesions.  He was previously stated to be cured when he finished the WHO stated duration of medication.  WHO official statement of relapse is very low so makes the present policy (of PB and MB drug routines) seem effective.  I know that most of the real LL, and BL patients I treat have much more anti-leprosy medication that the stated 12 months.  We do not want relapses in our clinics.

Hence I agree - - What is paucibacillary leprosy?- - by definition it is those with few bacilli - - therefore those in whom the bacilli have not yet been able to multiply frequently because of the short duration of infection eg. as in Indeterminate (I) leprosy- or those who have enough natural resistance to have been able to produce effective T lymphocytes to control the infection so the numbers cannot become great.  In both of these situations I feel we need to follow up the patient at least for several years to make sure that they really are cured, if we give the 6 months double drug therapy.

Let’s really control the infection by ensuring that those we do diagnose are fully treated to eliminate their infection.  Let’s over-treat not under-treat.

Yours sincerely,

Grace  Warren

Sydney, Australia

Previously Adviser for The Leprosy Mission In Asia (1975-95)

Treatment of reactions sometimes needs to be extended more than 6 months

Leprosy Mailing List – May 21^st, 2011

Ref:    Treatment of reactions sometimes needs to be extended more than 6 months.

From: W. J. Theuvenet, Apeldoorn, The Netherlands

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Dear Dr. Naafs,

Thank you for your valuable observation (LML May 18^th, 2011) that reactions often need treatment longer than 6 months.  This covers my personal experience.  In my last borderline leprosy (BL) patient the neuritis of several nerves frequently recurred in the first 24 months after putting her on MDT/ Prednisone and an increased dosage of clofazimine.  Most of the nerve(s) function responded very well on this regimen and over this period she could never really do without varying dosages of the prednisone/clofazimine, this modulating with the severity of the neuritis.  The right tibial nerve was decompressed (by the "selective meshing of the epineurium" method) at the tarsal tunnel as it did not respond within 4 months on this regimen and sensation was restored within 2 weeks after operation!  From Semmes Weinstein Monofilament (SWM) test 6.65 negative to 4.31 positive at the vulnerable Hallux andfirst metatarsophalangeal (MTP) -1 area.

Personally I feel that more research is needed as the present neuritis treatment even when applied with a longer duration, often gives some "improvement" of nerve function, but this "improvement" is hardly ever back to a functional level, be it to full restoration of nerve function.  In this situation it is sad that there is very little attention paid to the alternative of a nerve decompression.  To operate on a nerve ("nerve decompression") seems to frighten the ignorant but it is not "brain surgery" and provides often a simple alternative for the restoration of nerve function where medical treatment fails.

TENLEP may offer valuable information and any new research is welcome, as nowadays permanent nerve function loss is often too easily accepted as a consequence of leprosy.  Without this nerve function loss there would hardly be any need for stigma reduction, community based rehabilitation, empowerment etc etc.  We therefore urgently need better tools to properly treat leprosy neuritis!

With best regards,

Willem J. Theuvenet.

Management of Type I reaction (reversal reaction)

Leprosy Mailing List – May 13^th, 2011 

Ref:    Management of Type I reaction (reversal reaction)

From: P. Saunderson, Greenville, SC, USA

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Dear Salvatore,

In relation to the management of Type 1 reactions, I would like to make a few comments:

1.    There is general agreement that steroid treatment probably needs to be longer than 12 weeks, although 30-40 mg seems to be an adequate starting dose.  There is a need for better evidence from well-designed clinical trials, before we can state clearly what is the best routine treatment for Type 1 reactions.

2.    A good starting point for discussion at the moment is the paper by Rao PS, Sugamaran DS, Richard J, Smith WC: Multi-centre, double blind, randomized trial of three steroid regimens in the treatment of type-1 reactions in leprosy.  Lepr Rev. 2006 Mar;77(1):25-33.  The paper is attached.

3.    On the basis of this paper, The Leprosy Mission now advocates the 20 week regimen tested in the trial, namely: prednisolone 30mg for 2 weeks, 25mg for 2 weeks, 20mg for 8 weeks, 10 mg for 4 weeks, 5mg for 4 weeks.  The aim is to extend the length of the course, but keep the total dose of prednisolone as low as possible.

4.    A new randomized, controlled trial is just about to start under the name ‘TENLEP’ (Treatment of Early Neuritis in Leprosy), which is a multi-center study managed by the Royal Tropical Institute (KIT) in Amsterdam.  This study will compare a 20 week regimen with a 32 week regimen in the treatment of new nerve function impairment, which is closely related to the occurrence of a Type 1 reaction.

Paul Saunderson MD, MRCP

Medical Director

American Leprosy Missions

1 ALM Way, Greenville, SC 29601, USA

Leprosy Mailing List – May 11^th, 2011 

Ref:    Management of Type I reaction (reversal reaction)

From: W. S. Bhatki, Santacruze (E), Mumbai, India

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Dear Dr Noto,
Though the standard treatment for management of leprosy reactions is laid down, the same cannot be practiced in all the cases.  The clinicians who actually handle the cases with leprosy reactions have often to decide the line of treatment, based on the response in individual cases.  I report herewith about “Difficulties in management of Type I leprosy reaction with facial lesions”.

I came across three cases (photographs enclosed below) with solitary, medium sized, raised, erythematous, plaque-like anaesthetic facial lesions. The patients received paucibacillary multy-drug therapy (PB/MDT) for 6 months and steroid therapy in tapering doses.  All of them were skin smear negative.  No biopsies were done. The three photographs (enclosed) were taken after these patients were referred to us after completing their course of PB/ MDT, and because of suffering from 1-2 episodes of reaction without satisfactory result while on steroids as described below.

The initial response to prednisolone with daily dose of 40 mg was good as the lesions showed noticeable regression. The dose of prednisolone was tapered by 5-10 mg every 2 weeks.  The lesions recurred with erythema and oedema when the daily dose of prednisolone was brought down to around 15-20 mg; this forced the clinician to raise the daily dose to 30 mg or more.  This phenomenon occurred repeatedly in the cases under reference. 

In the context of fluctuating clinical response, the clinicians often face problems such as:

1.    The total duration of steroid therapy is much more extended beyond the usually advocated period of 12 weeks posing a threat of serious side effects.

2.    The clinicians are often inclined to extend the period of MDT beyond 6 months or sometimes even switch over to multibacillary (MB) MDT.

3.    Due to repeated recurrence of face lesions, the case holding becomes difficult as the patients tend to change the doctors.

Steroid treatment (prednisolone) is still considered the treatment of choice for Type I reaction with the starting daily dose of 30-40 mg.  However, the duration of treatment could be a matter of debate.  I would like to have the opinions and the advice from colleagues on this and the issues mentioned above especially with reference to face lesions which could cause severe psychological distress to the affected persons.

Regards,

Dr. W. S. Bhatki

Maharashtra Lokhita Seva Mandal

Santacruze (E), Mumbai, India

Check images on: http://www.aifo.it/english/resources/online/lml-archives/2011/110511.htm

Assumption: “ENL is a process by which the human body wants to clean up all "foreign bodies" including leprosy bacilli fragments”

Leprosy Mailing List – April 6^th, 2011 

Ref:    Assumption: “ENL is a process by which the human body wants to clean up all "foreign bodies" including leprosy bacilli fragments”.

From: Terence Ryan, Oxford, UK

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Dear Salvatore,

I am in full accord with Indropo Agnusi – LML 25-03-2011.

I used to write reviews of Immune complex diseases and emphasised that efficient elimination of antigen required an excess of antibody with complement and in the case of Henoch Schoenlein Purpura in children, steroids should be avoided to allow the good effect of complexing.  Bed rest and perhaps an aspirin would be enough unless the kidneys were involved.

Terence Ryan