Leprosy Mailing List Blog: September 2010

Wednesday, September 29, 2010

Prof. Terence Ryan's concern

Leprosy Mailing List – September 28^th, 2010

Ref.: Prof. Terence Ryan's concern.

From: R Ganapati, Mumbai, India

Dear Dr Noto,

I appreciate Prof. Terence Ryan's views (LML Sept. 25^th, 2010) on the claims of WHO on "leprosy elimination". I have recorded my observations on the Indian scenario many times in LMLs. The index prepared by Dr Sunil Deepak [Leprosy LML archives] may contain these. I am enclosing some more material (page 1, page 2, page 3) for the attention of Prof. Ryan as well as your readers.

Yours sincerely,

R Ganapati,

Director Emeritus, Bombay Leprosy Project

Clofazimine and erythema nodosum leprosum (ENL or type 2) reaction

Leprosy Mailing List – September 28^th, 2010

Ref.: Clofazimine and erythema nodosum leprosum (ENL or type 2) reaction.

From: H K Kar, New Delhi, India

Dear Dr Maria Leide,

Thank you very much for your message dated LML Sept. 25^th, 2010. I agree with you fully regarding possibility of development of resistance due to use of clofazimine alone for management of late type 2 reaction after multi-drug therapy (MDT). We are all aware of the fact that high bacteriological index (BI) is associated with relapse as well as late recurrent ENL reaction in lepromatous (LL) patients. The 12 MONTHS MDT for multibacillary (MB) patients may not be sufficient to kill all live bacilli, particularly with higher BI, more than 4+. There is always chance of relapse in those cases with clofazimine resistant bacilli. Therefore, in those cases it is ideal to continue MDT-MB along with higher dose of clofazimine for treatment of ENL.

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

India

Reference required

Leprosy Mailing List – September 25^th, 2010

Ref.: Reference required.

From: Terence Ryan, Oxford, UK

Dear Salvatore,

I continue to receive anecdotes from concerned workers in the field of leprosy that Governance is not tackling the problem of the continuing existence of leprosy both as an active bacterial infection and as a presentation of disability. This is usually because the term elimination is taken to mean it no longer exists. I have a personal experience of Government employees cancelling my request for a biopsy, and of failure to refer on data on new cases to WHO in both India and in Africa.

The reason for this email is to seek evidence that, from the highest level, Governments in Asia and Africa are being told that elimination does not mean eradication and that there are still new cases which must be treated if elimination is to mean no longer a public health problem. I would value a reference I could quote from for example the WHO so I can respond in answer to these anecdotes and I can say "OK don’t worry it is a problem that is being addressed and here is reference proving it”. Hand it on to those who will not provide MDT or are discarding your data.

I would also like to read in the Neglected Tropical Disease (NTD) literature not just that Leprosy is included but that it is very much in need of as much advocacy and continued funding as Malaria, TB, AIDs and the NTDs which currently seem to have more energy devoted to them. My reading of the NTD literature suggests to me that their governance could be made more aware that we still have a problem to be solved.

Sincerely

Terence Ryan

Emeritus Professor of Dermatology Oxford University and Oxford Brookes University

Clofazimine in high dosage used for the treatment of late ENL reaction in leprosy: could it mask a relapse?

Leprosy Mailing List – September 25^th, 2010

Ref.: Clofazimine in high dosage used for the treatment of late ENL reaction in leprosy: could it mask a relapse?

From: Maria Leide W. de Oliveira, Rio de Janeiro, Brazil

Dear Dr Noto,

I have been following all the discussion regarding clofazimine with my colleagues in LML and the following is my point of view:

1- As reported by some Leprosy Control Program managers, Brazil too has been receiving loose clofazimine (100mg and 50mg capsules) for the past years from WHO Geneva free of charge. However, it is not a regular allocation and the total delivered has been inferior to our requests.

For this reason, the National Hansen’s Disease Control Program has manifested the desire to buy loose clofazimine. Another reason is to avoid the misusing of MDT blister-packs by extracting the 50 mg clofazimine capsules from the MB blister-packs and discarding the DDS and rifampicine or using it for other purposes.

2- In field work I use to prescribe clofazimine in many leprosy cases. As in

Brazil

we have Thalidomide available and its dramatic effect in type 2 reaction is undoubtedly superior to the action of clofazimine, I only use it in a high doses to treat recurrent type 2 reactions, usually in late reaction after polychemotherapy or in some young women. However, after my latest experience with relapse cases I started wondering if clofazimine is not masking relapse development and also, creating a risk of clofazimine resistance due to its mono-therapy. We must protect this wonderful drug from now on. Therefore, I am avoiding giving clofazimine in late type 2 reactions and have started observing those cases where clofazimine was given previously.

Best regards,

Maria Leide W. de Oliveira

Medical School-UFRJ-Brazil

mleide(at)uol.com.br - mleide(at)hucff.ufrj.br

Clofazimine in ENL

Leprosy Mailing List – September 22nd, 2010

Ref.: Clofazimine in ENL

From: Willem Theuvenet, Apeldoorn, The Netherlands

Dear Salvatore,

In addition to the valuable comments of Pieter Schreuders and Ben Naafs (LML Sept. 2^nd 2010): I fully agree on their comments. Perhaps a word of caution in those cases of chronic recurrent ENL when a prolonged regime of Clofazamine needs to be combined with corticosteroids. In that situation there is definitely an increased risk of drug induced gastro-intestinal bleeding. This risk is further increased when analgetics are added.

These patients should be carefully monitored for this potential life threatening complication.

With best regards,

Willem Theuvenet

Indeterminate leprosy

Leprosy Mailing List – September 17^th, 2010

Ref.: Indeterminate leprosy

From: Shumin Chen, Jinan, Shandong, China

Dear Dr Noto,

Indeterminate leprosy is difficult in diagnosis both clinically and pathologically (G. Warren LML Mar. 28th, 2010). When a case is suspected and pathological examination shows negative AFB, series slices should be made and careful looking for destroyed neurofibres; an evidence for nerve damage, which may be helpful in the diagnosis of indeterminate leprosy. When necessary, S-100 protein staining should be made in confirmation of nerve damage.

About the usefulness of dermal nerve damage and S-100 protein in the early diagnosis of leprosy, some papers on this topic in Medline can be found. Here are two examples related to the diagnosis of indeterminate leprosy: 1. Weng XY, et al. Immuo-histopatholgy in the diagnosis of early leprosy. Int J Lepr, 1999; 68(4):426-433. 2. Gupta SK, et al. S-100 protein as a useful auxiliary diagnostic aid in tuberculoid leprosy. J Cutan Pathol, 2006; 33(7):482-486.

In the textbook of "Leprosy" edited by Hastings, we can find following description regarding the diagnosis of indeterminate leprosy: Histologically there is a scattered infiltration of lymphocytes and histocytes around skin appendages, peripheral nerves and vessels which is diagnosable as leprosy in cases exhibiting a cellular reaction within a dermal nerve, .......(p 91).

In Shandong, when a suspected indeterminate leprosy, difficult case, is found, we usually take one out two strategies in dealing with the patient. One is to treat, the case with MDT and follow up to see the change of the skin lesion, but not label him or her, (as also suggested by Dr Warren). Another strategy is just to closely follow up (no treatment) to see the change, and then, action will be taken accordingly.

Sincerely yours,

Dr. Shumin Chen

Shandong provincial Institute of Dermatology

Jinan, Shandong, China

About the many aspects of the proper treatment of ENL

Leprosy Mailing List – September 12^th, 2010

Ref.: About the many aspects of the proper treatment of ENL

From: A Pongtiku, Jayapura, Papua, Indonesia

Dear Dr Noto,

Thank you very much for bringing the issue of chronic ENL and steroid dependent ENL. Thank you very much also to the experts that have commented about this important issue. I remember one senior dermatologist saying that these are among the most difficult problems in treating leprosy patient.

Indonesia

for steroid dependent ENL, we used prednisolone tapering off and substituted with clofazimine high dose 3 x100 mg for 2 months and continued 2 x 100 mg for 2 months and 1 x 100 mg for 2 months. It should be noted that the effect of clofazimine will be evident after 1 month of therapy; so we should think for prednisolone when tapering off. Prednisolone is still needed for at least a month, in our protocol for adult case, we start 40 mg and tapering off every two week. In Papua,

Indonesia

, many triggered factors for ENL are present like malaria, dental problems, psychological problems, anaemia, under-nutrition.

I have treated few successful cases with the above reported protocol including 2 cases with steroid depended AIDS due to ENL reaction. We tapered off prednisolone faster (decreased dose of prednisolone every 5 days) and at the same time added clofazimine. Accurate case holding and home visits are necessary to support the patient.

It is important to think about BI (Bacterial Index) when BI is high more than 4 +, it is more possible to develop ENL. In few ENL reactions that developed after treatment with MDT for 12 months, we found still high Morphological Index (solid type of bacteria).

I agree with Dr Warren (LML Sept. 10^th, 2010) about prednisolone is dangerous if not managed well. Some patients died because of self administration of this drug. Prednisolone can be easily bought in drug store without prescription in Indonesia. Many leprosy patients feel secure/better with prednisolone so they may go for self administration.

Now, together with a dermatologist and I, we are treating a leprosy patient with a steroid dependent ENL reaction of more than a year used and already finished MDT a year ago. We used the protocol of prednisolone tapering off and substitution with clofazimine. Because of still BI 3+ and 4+ as well as MI 70%, we also retreated with MDT. However complication of gastrointestinal upset/vomiting occurred at fourth week (3 times hospitalization). We then stopped high clofazimine. We tried to give MDT after a week but vomiting appeared again. Now, we used methylprednisolone the patient looks better. We still wait until stable condition and continue to retreat with other anti leprosy.

Finally, I would like to say: "when we recommend the use of steroid for the management of patients in reaction we/medical staff must be responsible for tapering off ".

Thank you very much,

Dr. Arry Pongtiku, MHM

National Consultant for Leprosy and Yaws in Papua and West Papua, Indonesia

Netherlands

Leprosy Relief Indonesia

About the many aspects of the proper treatment of ENL

Leprosy Mailing List – September 10^th, 2010

Ref.: About the many aspects of the proper treatment of ENL

From: G. Warren, Sidney, Australia

Dear Salvatore,

I refer to Pieter Schreuder’s message dated LML Sept. 2nd, 2010. I would like it to get to the younger folk some of whom throw prednisolone around like sweets, as it is was the answer to everything and do not realise the complications and how much it can shut down a lot of the bodies natural ability to cope with inflammation etc.

For the sake of those who are involved in the care of severe erythema nodosum leprosum (ENL) reaction especially in light skinned patients, I would like to add to Dr Schreuder’s comments:- Yes, clofazimine at doses as he suggests (starting with 300mg per day and till off all steroids) is highly successful. I also worked in Thailand and we had dozens of patients who had been treated with prednisolone for ENL, before they came to us and we eventually got them off the prednisolone and stabilised on clofazimine with all ENL controlled and stable till completely bacteria negative. However the light skinned patients often do not like the dark colour that develops but if it is properly explained and they see others who can confirm that the colour will fade later they will usually accept it especially if they do have severe ENL.

In those days we usually gave clofazimine as mono-therapy – it was before MDT recommendations - and I was involved in some of the original drug trials of clofazimine and if I only had one drug to treat leprosy I would use clofazimine. I have never seen a patient become resistant to it even when given as mono-therapy for a long period, and although I understand resistant bacilli have been developed in laboratories they, as far as I know, have never developed in a patient (*).

Working in third world countries for many years I also know the problems of prednisolone and know that many patients are given it unnecessarily. This concerns me as I have seen many patients who have died because of the use or was it abuse, of prednisolone. In countries where it can be bought without a doctors prescription we find that patients self medicate, with prednisolone because it “makes them feel good”, and we have had many patients with undesirable complications. Patients that I consider could have been treated with less or no prednisolone. Some have died after they officially finished prednisolone because within the period needed for their own adrenal function to be restored, they developed some other medical condition that should have been treated with more prednisolone but that was not given and the patient died.

Personally I have learnt how to manage most ENL without prednisolone and do so if at all possible, because many patients live where it is not easy to access good medical care in the prolonged period needed to restore their normal immune ability after the prednisolone has finished. An important point is to find, diagnose and treat any other medical condition that may in fact be responsible for or contribute to the problem of the ENL (eg anaemia and parasites). In many patients the adequate treatment of tuberculosis or malaria or chronic typhoid will “cure” the ENL, and minimise the risk for post treatment complications.

Hope that this helps some adapt to difficult circumstances.

Grace Warren

Previously Adviser in leprosy and reconstructive surgery for The Leprosy Mission in Asia.

*(note by S. Noto)

Titia Warndorff-van Dieden, “Clofazimine-resistant leprosy, a case report”

International journal of leprosy and other mycobacterial diseases, volume 50, number 2 June 1982

Pieter Schreuder joins the LML staff

Leprosy Mailing List – September 8^th, 2010

Ref.: Pieter Schreuder joins the LML staff

From: S Noto, Genoa, Italy

Dear All,

I am very happy to announce that Pieter Schreuder has joined the LML staff (that is to say myself and Sunil Deepak). This was needed, because the editing took to much time for one man alone. Practically there will be no differences. I will receive and circulate papers and messages and Sunil will manage the Archives of the LML. But, some of the editing activity that is between the reception of the messages and their circulation will be taken care of by Pieter. I am sure that in this way we are able to continue, moreover we are going to gain in skills and time.

Best regards,

Salvatore

4th CAN International Conference on Community-Based Rehabilitation. 26th – 29th October, 2010, Abuja, Nigeria

Leprosy Mailing List – September 4^th, 2010

Ref.: 4^th CAN International Conference on Community-Based Rehabilitation. 26^th – 29^th October, 2010, Abuja, Nigeria

From: S O Udo, Abuja, Nigeria

Theme: Linking CBR, with Disability and Rehabilitation and Launching of the WHO/CBR Guidelines.

Dear Salvatore,

Kindly circulate among LML readers the attachment announcement.

Thanks,

S O Udo

TLMI Nigeria

Prednisolone does not reduce the effectiveness of rifampicin

Leprosy Mailing List – September 3^rd, 2010

Ref.: Prednisolone does not reduce the effectiveness of rifampicin

From: Wim van Brakel, Amsterdam, The Netherlands

Dear Salvatore,

Dr. Shetty’s group in Mumbai just published a major study in the March issue of leprosy Review this year presenting hard evidence that prednisolone use does NOT increase the risk of relapse, i.e. does not reduce the effectiveness of rifampicin. There is no need, therefore, to prolong MDT in patients receiving steroid treatment for reactions.

With best wishes,

Wim

Wim van Brakel, MD,MSc,PhD
Senior Advisor
KIT Development Policy & Practice
Leprosy Unit
T +31 (0)20 6939297
Royal Tropical Institute
Amsterdam
The Netherlands
F +31 (0)20 568 8444
www.kit.nl / www.kit.nl/100

Clofazimine in recurrent type 2 (ENL) leprosy reaction

Leprosy Mailing List – September 3^rd, 2010

Ref.: Clofazimine in recurrent type 2 (ENL) leprosy reaction.

From: Indra Napit, Anandaban, Nepal

Dear Dr. Noto,

Greetings from Anandaban hospital, Nepal. We also use Clofazimine often for recurrent, chronic or steroid dependent ENL reactions as many other collegues have mentioned. It is availbale in our hospital, we buy it from

India

We use following protocol:-

Clofazimine 300 mg daily for 2 months, then 200 mg daily for 2 months and 100 mg daily for 2 months or until the symptoms persists.

We have realized that Clofazimine helps to reduce the daily requirement of steroids in recurrent ENL reactions. Occasionally there is problem of acceptance by patients due to pigmentary changes, dryness of skin and gastrointestinal upset.

I would like to attract your attention on the sentence written by Francesca Gajete from Cebu, Philippines:- "We get our supply of loose Clofazimine both 100mg and 50 mg capsules from WHO, Geneva, through Dr Steve Lyons".

Can we also get the supply of loose Clofazimine from WHO?

With regards,

Dr. Indra Napit

Medical Superintendent

Anandaban Hospital,

Nepal

Clofazimine in recurrent type 2 (ENL) leprosy reaction

Leprosy Mailing List – September 2^nd, 2010

Ref.: Clofazimine in recurrent type 2 (ENL) leprosy reaction.

From: Pieter AM Schreuder, Maastricht, The Netherlands

Dear Dr. Romero,

Thank you very much for your message dated LML Aug. 29th, 2010. May I refer you to the following:

Chronic recurrent ENL, steroid dependent: long-term treatment with high dose clofazimine. Schreuder PA, Naafs B.Lepr Rev. 2003 Dec;74(4):386-9

Just to quote one paragraph:

"Patients who develop several bouts of ENL over a short period of time should be prescribed a high dose of clofazimine with a starting dose of 300mg daily for at least 2 months, together with drugs to relieve the acute symptoms (e.g. steroids). When a patient continues having ENL reactions, 200-300 mg daily should be maintained for longer periods, and if the patient is on steroids, the steroids should be reduced slowly (to zero) under the protective umbrella of clofazimine. When thalidomide is available and can be prescribed, it could be used or added to replace the steroids. If no new ENL reactions appear and the patient is no longer on steroids, clofazimine can slowly be reduced to 200mg daily for 2 months, to 100mg daily for 2 months, etc. Clofazimine can be given in high doses over long periods to wean dependent patients from steroids."

Thailand

, we did not have thalidomide, and basically had only two drugs: steroids and clofazimine. A course of high doses clofazimine as mentioned above was used with excellent results in chronic ENL and steroids dependent ENL. However, in some cases it took one year to wean the patient from the steroids. I also remember several patients on high dose clofazimine with a long history of chronic ENL who refused when I wanted to reduce the clofazimine fearing that the ENL would come back.

Kind regards,

Pieter AM Schreuder

Clofazimine in recurrent type 2 (ENL) leprosy reaction

Leprosy Mailing List – September 2^nd, 2010

Ref.: Clofazimine in recurrent type 2 (ENL) leprosy reaction.

From: B Naafs, Munnekeburen, The Netherlands

Dear Dr Ailton,

Thank you very much for your message dated LML Aug. 29^th, 2007. I agree with the positive effect of lamprene (clofazimine) on recurrent ENL. It is still one of the drugs I use for this severe condition. Pieter Schreuder and I wrote a small letter to the editor about this:-
P.A.M. Schreuder and B. Naafs. Chronic recurrent ENL, steroid dependant: Long-term treatment with high dose of clofazimine. Lepr. Rev. 74 (2003) 386-389

This paper can be accessed via the Website of leprosy review. I have to admit that there is "no scientific evidence", but I believe you, and I have seen good results too.

The major argument against the success of lamprene is the time frame. Would it not have abated by its own?

I hope more colleagues will respond.

With kind regards,

Ben Naafs

Clofazimine in recurrent or chronic or steroid dependent type 2 leprosy reaction

Leprosy Mailing List – September 2^nd, 2010

Ref.: Clofazimine in recurrent or chronic or steroid dependent type 2 leprosy reaction.

From: H K Kar, New Delhi, India

Dear Dr Noto,

We agree with Dr Romero (LML Aug. 29^th, 2010) that clofazimine is a very good drug for management of recurrent or chronic or steroid dependent type 2 leprosy reaction. However, we prefer to give a longer duration of clofazimine (CLF) with gradual tapering in steroid dependent cases.

e.g.

CLF 300mg daily daily for 3 months followed by 200 mg for 3 months followed by 100mg daily as long as symtoms persist

plus
prednisolone in dose of 30 mg daily for 2 weeks followed by 25 mg daily 2 weeks followed by 20 mg for 2weeks followed by 15 mg daily for 2 weeks followed by 10 mg daily for 2 weeks followed by 5 mg daily for 2 weeks, then stop.

Majority of cases respond to this regimen if thalidomide is not available or if not affordable.

Side effects with high dose of CLF when given for a longer period like chronic abdominal pain, diarrhoea and rarely partial or complete bowel obstruction may develop. In that case the drug should be stopped immediately. Gradually decreasing the dose of CLF should prevent these complications.

Fortunately this drug is available separately for use in reaction in India.

Reference:
Management of leprosy reactions in IAL Text book of Leprosy. 1st edition (2010) edited by H K Kar and Bhushan Kumar, published by Jaypee brothers medical publishers (P) LTD, chapter 30; page:395.

(E-mail: jaipee(at)jaypeebrothers.com, Website:www.jaypeebrothers.com)

telephone:+91-11-23272143, Fax: 91-11-23276490

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

India

Prednisolone changes the rifampicin effectiveness?

Leprosy Mailing List – September 2^nd, 2010

Ref.: Prednisolone changes the rifampicin effectiveness?

From: Grace Warren, Chatswood, Sydney, Australia

Dear Salvatore,

I am interested in the comment by Elyzabeth Duncan (LML Aug. 29^th, 2010). I have not heard from her for a long time!

Good on her to define the change in prednisolone effectiveness. I would say the prednisolone changes the rifampicin effectiveness. Can anyone tell us which is correct? As I know that when I give prednisolone I must MUST give the MDT for longer.

Grace

Clofazimine in ENL reaction

Leprosy Mailing List – September 2^nd, 2010

Ref.: Clofazimine in ENL reaction

From: Francesca Gajete, Cebu, Philippines

Dear Dr Romero,

Thank you for your message dated LML Aug. 29^th, 2010. In our (8) Sanitaria including the Skin Clinic of Leonard Wood Memorial Research in Leprosy in Cebu, Philippines and occasionally in the field the combination of Prednisone and Clofazimine using the standard WHO regimen has successfully controlled recurrent ENL. We have also been using Clofazimine in those patients who have contraindications for Prednisone use.

We get our supply of loose Clofazimine both 100mg and 50 mg capsules from WHO, Geneva, through Dr Steve Lyons.

Francesca Gajete

National Leprosy Control Program

Philippines

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Wednesday, September 29, 2010