Monday, December 30, 2013

(LML) Thalidomide in treating kidney involvement in ENL

Leprosy Mailing List – December 30,  2013 

Ref.:    (LML) Thalidomide in treating kidney involvement in ENL

From:  Dr. HK Kar, New Delhi, India

 

Dear Dr Pieter,

 

 

I would like to refer to the discussion Dr. Jingquan Wang started in LML: Thalidomide in treating kidney involvement in ENL. It is an interesting letter on management of chronic/recurrent ENL. As you observed in China, in India also, we encounter more number of recurrent ENL rather than chronic ENL. This could be  either due to  inadequate or short course of   anti-reactional therapy using conventional  available anti-leprosy drugs. Recently we presented a paper in 18th Int. leprosy congress, Brussels, Sept. 2013(0-069).

 

 

Treatment of Chronic and recurrent type 2 reaction (T2R)

Drug regimens:

A combination of prednisolone plus thalidomide or clofazimine is preferable for management of chronic and recurrent T2R. The ideal duration and dose of steroid and other drug combinations   is still a matter of debate. An open prospective single centre study in our institute  was conducted  to assess the comparative efficacy of  combination of prednisolone plus thalidomide in one group v/s prednisolone with clofazimine in another group  in  chronic and recurrent T2R

 

 

Prednisolone was given in the dose of  1 mg/kg/day to start with, then gradually tapered as (10 mg every 2 weeks up to 30 mg, than 5 mg every 2 weeks up to 5 mg, then 2.5mg for 2weeks -for a total of 20 weeks)  plus  either Thalidomide (400 mg daily x 7days  and then tapered by 100mg every month to a dose of 100mg daily, then every alternate day for a total period of 20 weeks) or Clofazamine (300 mg/day to start  and then 300 mg x 12 wks, 200 mg/day x 4 wks, then 100 mg/day x 4 wks given over 20 wks).

 

Patients were followed up for 6 months after 20 weeks course of treatment to note any further recurrence of T2R. The response rate based on the clinical outcome was 82.35% in thalidomide plus prednisolone group and 60% in clofazimine and prednisolone group.  In the follow up period of 6 months, 2 of 16 patients in prednisolone plus clofazimine group  developed fresh episode of T2R where as none (0/17) in the prednisolone plus thalidomide group had recurrence. It was concluded that thalidomide has good efficacy when administered in combination with prednisolone for chronic and recurrent T2R. Clofazamine has a definite role when thalidomide cannot be administered (women in child bearing age). The duration of combination treatment  should be judged depending on the  frequency of recurrence of lesions.

 A few individual cases of chronic ENL may need more than 20 weeks anti-reactional treatment to control the reaction fully.

A recent study from Bangladesh showed that  nine  cases of recurrent/chronic ENL not controlled by a combination of prednisolone with clofazimine could be managed with a combination of prednisolone with methotrexate (prednisolone dose: 40 mg/day x 3 months, reduced to 20 mg/day x 3 months, then reduced by 5mg/wk x 3 months, reduced by 5mg a/d, then weekly twice, then weekly once: 30 to 36 months (total) and methotrexate dose: 7.5 mg/wk: 24-30 months). 

The treatment regimen is individualized depending on the complications associated with Type 2 reaction (ENL) like kidney complications, diabetes, pregnancy, steroid side effects. We also encountered a case of DVT in one case under prednisolone with thalidomide. This type case report has already been publishes earlier.

 

With Regards

 

 

Dr (Prof.) H K Kar\

Professor in Dermatology and Leprosy
Director and Med. Superintendent
P.G.I.M.E.R. and Dr Ram Manohar Lohia Hospital
Baba Kharag Singh Marg
New Delhi-110001

 

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com



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(LML) Thalidomide in treating kidney involvement in ENL

Leprosy Mailing List – December 30,  2013 

Ref.:    (LML) Thalidomide in treating kidney involvement in ENL

From:  Grace Warren, Sidney, Australia

 

 

Dear Pieter,


I am very interested in the letters of Dr. Jingquan Wang and the progress of his patient.  You ask why thalidomide and steroids are not recommended more for lepra reaction.  I was working In Hong Kong for 15 years including all the 1960s when  we started by using thalidomide to treat reaction but as the decade wore on the problems of foetal abnormality after use of thalidomide resulted in it being very difficult to obtain it anywhere except in  S America. In fact it was banned in some countries. 

 

We also realized the tendency for the patients with ENL to become dependent on steroids if they were used alone. So we tried using many variations of drugs available at that time and found some of them did produce undesirable side effects.  However,  I was also involved in the drug trials for  clofazimine  (we started in about 1966)  and we soon found that clofazimine was excellent in  treatment of ENL.  In very  heavy  patients or when the reaction was very severe, we often went as high as 300mgms daily for the first month but usually 200mgms daily was enough. When initiating the antileprosy treatment we did not give, except clofazimine, the other anti-leprosy drugs  for 4-6 weeks, during which time we treated other medical problems like anemia and parasites and malnutrition.  We found that this was excellent in managing new patients with LL leprosy and a tendency to ENL before even starting antileprosy therapy. Of course by 1970 no one had even thought of MDT. We also regularly gave a good dose of multivitamins especially Vit. B 1 as many were short of that due to the maintenance on white rice in which of course most of the Vit. B1 is removed in preparation and  milling.  We were able to do well controlled pathology testing that showed that  clofazimine certainly helped liver function and also did not  usually produce   the problems we saw with some  other drugs that were used in those days.

 

In treating chronic ENL it  was found that clofazamine was usually very effective. We would give 200mgms daily with some form of  relaxant like  valium or just phenobarb  or  amitriptyline  as many of the patients went into reaction because of stress and  worry about their  families. Once it was known that a member of the family had leprosy, the rest of the family were excluded from the community. Clofazamine is of course bacteriostatic and also anti-inflammatory, and in some situations acts as an antibiotic. Once the patient’s condition was  stabilized we would give the other antileprosy drugs and continue using it in lower dosage for the whole duration of treatment.

 

I have treated leprosy in  26 countries of the world and agree that of the many races that I have treated  the Chinese do seem to be those who most  frequently develop  very chronic or long term ENL. I also found that in many countries the use of steroids may lead to unwanted problems as  the patient can often purchase it themselves and continue it when the doctor concerned has tried to stop it. This can of course produce other problems that we do not want to have to treat. I could give many  examples of  patients who have died because of secondary problems they have developed because they were taking  unsupervised  steroids for prolonged periods . As I result I try as far as possible to only use steroids for acute neural deficit or  for a very short term initially in a patient with severe reaction at initiation of therapy.

Yes, I am thoroughly convinced that clofazimine is an ideal drug in the treatment of lepra reaction especially ENL  but when combined with other drugs  can assist in the management of any lepra reaction.

Grace  Warren.
Superintendent Hong Kong Leprosarium( 1960-1975)
Adviser on Leprosy, and Reconstructive surgery  for The Leprosy Mission , 1975-1989)

 

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com

 



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Wednesday, December 25, 2013

(LML) Thalidomide in treating kidney involvement in ENL

Leprosy Mailing List – December 25,  2013 

Ref.:    (LML) Thalidomide in treating kidney involvement in ENL

From:  Jingquan Wang, Zhejiang, China

Dear Pieter Schreuder and Ben Naafs,


Thanks for Dr Ben Naafs quick response and good comment on Dec 20,2013.The female patient has improved in kidney function. The recent routine urine test showed the erythrocytes in the urine had disappeared and leucocytes in the urine still present with 26 leucocytes(normal:0-10). Although we did not take any culture,  we still concluded that the patient accompanied with urinary tract infection,  besides the ENL inflammation in the kidney. We will prescribe new drugs such as minocycline (some experts say it has the effect to control ENL) to treat the infection with over 7 days. While the patient was on treatment for ENL and urinary tract infection, the patient had no  colic pains and ureter stones can be excluded. On admission day, the urine test showed no any leucocyte or erythrocyte in the urine besides albuminuria.


In my experience, triptolide is a good drug to relieve nerve pains and kidney damage, which is widely used to treat moderate to severe ENL cases or those steroid dependent ENL cases. Triptolite combined with prednisone has a long history of treating ENL in China since 1970s. Dr.  Shen Jianping and Dr. Yan Liangbin made a trial to compare the effects of group triptolide alone (A) and group of triptolide and prednisone combination (B)T.  The dosage of triptolide in two groups was 60-80 mg daily for four weeks in the hospital and then tapered the dosage for another four weeks at home. The patients in group B received prednisone besides the same triptolide as in group B. The results showed there was no differences in symptoms,   improvement and recurrence rate ENL between two groups. The general score of clinical status for 18 patients in group A decreased from 10.94 to 0.94 (4 weeks) and 1.44(8 weeks). The general scores for 16 patients in group B from 13.19 to 1.63 (4w) and 2.25 (8w). The recurrence ENL rates of two groups were both 50%, with an interval time of 7-60 days from stopping treatment or gradual reduction in group A and 7-20 days from the gradual  of triptolide 30-40 mg daily in group B. There were additional 2 patients who could not tolerate the drug (severe vomiting and nausea) and  dropped out the study. The remaining 34 ENL cases finished the study, with only one patient with mild nausea. The authors concluded that triptolide has a significant efficacy in treating ENL and it is necessary to make out a very slow tapering regimen to prevent ENL from recurrency.


By the way, how to define a chronic ENL case, of 3 months or 6 months duration? I feel that recurrent ENL cases were more common in China and chronic or continuous ENL cases lasting 2-3 years are relatively rare. Do you agree with me? I am very surprised why ILEP technical report of Issue No 9, revised April 2011 do not include the regime of  thalidomide +prednisone regime and do not give the advice on chronic  ENL treatment? It is a great default. Have anyone in LML circle participated in developing the advice?


Best regards.  


Jingquan Wang,
Chief physician
Institute of Dermatology of Zhejiang Province,
China,313200
E-mail:Jingquanwang.cn@hotmail.com

 

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com



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(LML) WHO Goodwill Ambassador's Newsletter No.65, December 2013

Leprosy Mailing List – December 25 ,  2013 

Ref.:  (LML)   WHO Goodwill Ambassador's Newsletter No.65, December 2013

 

From:  Hiroe Soyagimi, Sasakawa Memorial Health Foundation, Tokyo, Japan

 

Dear Dr. Schreuder and Friends,

 

 

Warm greetings from Sasakawa Memorial Health Foundation in Tokyo. We have uploaded our latest edition of "WHO Goodwill Ambassador's Newsletter No.65, December 2013" to our website. 

Please visit http://www.smhf.or.jp/e/ambassador/index.html to obtain electronic version of this issue. 

In this issue we feature articles about ....

Message from the Goodwill Ambassador- Cross-party Cooperation

Back on Their Feet -HANDA's mobile prosthesis workshop provides a timely service in China

Fighting Leprosy with Knowledge -Infolep is the place for information on leprosy and related subjects.

A Cruel Disease -Treatment with MDT is not the end of the story for many cured of leprosy.

Museum Piece -Shared Married Quarters

Pushing for Progress -The goodwill Ambassador returns to India to attend another leprosy stakeholders' meeting, this time in the high-burden stat of Uttar-Pradesh.

Typhoon Haiyan Hits Culion Hard -Appeal launched to help Philippines rebuild and recover. 

 

We hope you enjoy our latest Newsletter!


Hiroe Soyagimi

Sasakawa Memorial Health Foundation

*********************************************

Sasakawa Memorial Health Foundation

Nippon Zaidan Bldg., 1-2-2, Akasaka

Minato-ku, Tokyo, 107-0052, Japan

 

TEL: +81-3-6229-5377

FAX: +81-3-6229-5388

Our websight: http://www.smhf.or.jp/e/

Our blog: http://blog.canpan.info/hansenbyo/ 

 

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com



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Monday, December 23, 2013

(LML) Duration of MDT MB, relapses and re-infection

Leprosy Mailing List – December 23,  2013 

 

Ref.:    (LML) Duration of MDT MB, relapses and re-infection

From:  Jaison Barreto, ILSL Bauru, São Paulo, Brazil

Dear Pieter,

 

The problems I have seen and described are occuring every day, whether I’m  in the field or at the national reference centre where I work.  Details about situation of the leprosy in the field can be seen at the site of Brazilian DAHW (www.dahwmt.org.br).

 

Physicians do not know about leprosy, and, many times, do not want to learn about it, because if they do, they will have to attend the patients from their municipalities. Of course, there are still good willing professionals, but they are diminishing in number.

For the few physicians whose are still fighting against leprosy, it is a hard life: we have to fight against the disease, the problems the patients have, and also against the politicians from the area we live and work.

 

Ignorance, stigma and prejudice are still the rule, mainly at the Brazilian states where leprosy is proclaimed "eliminated". The concept that leprosy is eliminated in a municipality or in a state worsens this vicious circle and leads to neglecting leprosy. Health managers do not want to spend money on a disease they believe does not exist

 

The weakness of the WHO classification (only the number of skin  lesions, while the number of nerves involved is not important), also worsens this problem. Ridley, 40 years ago, showed that borderline patients tend to downgrading: most BL comes from BT, and most LL comes from BB/BL.

 

Is it right to treat a  patient, who has many bacilli inside his nerves and few in the skin and who has not the capacity of elimination of M. leprae from the nerves, with daily dapsone and monthly rifampin for 6 months only? We, clinicians and leprologists, see, today, that many high BI leprosy (LL/BL) patients are not cured with 12 doses. So, what can we say about regimens of 6 months for these patients?

 

The most recent and best cohort study was published by Katoch et al in 2008, who described that 70 patients with BB, BL and LL leprosy that were treated with MDT 12 doses plus Ofloxacin and Minocycline, still had a relapse rate of 5,7% (follow up 8-10 years). In my recent (2011) PhD thesis, in a 11 years follow-up cohort study of 46 LL patients, treated with 24 doses MDT, 91% were found clinically healed,9% was still clinically active. Of the 46 patients 27% still had laboratory signs of disease (positive bacilloscopy, serology or bacilli inside the nose)..

 

Of course, household contacts must be evaluated, or the number of doses does not matter at all because of reinfection. I remember a patient I saw, from the state of Mato Grosso: a married woman, treated with 24 doses, who "relapsed" 2 times in 10 years. She said that her husband had no problems: no complains, no patches, no lepromas, but also no eyebrows and no eyelashes and never diagnosed.

 

Fortunately, in Brazil, we are working hard, and try to change this situation, since the making-up of statistics, as well as centralization of diagnosis and treatment, used to be done in many countries, does not solve the problem. The Brazilian Ministry of Health stimulates activities at municipalities, in order to evaluate household contacts locally, in order to detect the problem at younger ages and early (eg children with indeterminate leprosy).

 

Best regards

 

Jaison

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com

 

 



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Friday, December 20, 2013

(LML) Novartis Foundation for Sustainable Development Symposium, Basel, 2013

Leprosy Mailing List – December 20,  2013 

Ref.:  (LML)  Novartis Foundation for Sustainable Development Symposium, Basel, 2013

From:  Felicity Bonham, ILEP, London, UK

Dear Pieter,

Readers of LML may be interested in full coverage, including presentations and webcast recording, of the most recent Symposium held in Basel by Novartis Foundation for Sustainable Development where participants discussed in depth the complex question: What does it take to eliminate a disease?

These are all available on the NFSD website.

Best,

 Felicity

Felicity Bonham

PA to the General Secretary

International Federation of Anti-Leprosy Associations
Working together for a world without leprosy

Tel: +44 (0)20 7602 6925 – Fax: +44 (0)20 7371 1621 – Website: www.ilep.org.uk

To get our updates, like us on Facebook: ILEPAntiLeprosy

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com



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(LML) Thalidomide in treating kidney involvement in ENL

Leprosy Mailing List – December 20 ,  2013 

Ref.:    (LML)  Thalidomide in treating kidney involvement in ENL

From:  Ben Naafs, Munnekesburen, the Netherlands

Dear dr Jingquan Wang,

 

Thank you for your quick response. I wonder did you do a culture (and sensitivity)? Are there colic pains? In other words, I think that you have to look for another cause for the blood and leucocytes in the urine.

 

Concerning the side effects of thalidomide yes, headache can occur, but the hypertension is most often pulmonary. But it could be wise to stop.

 

I understand GTW is a drug used in China for proteinuria, supressing male fertility and as a immunosuppressor.

 

I agree with you that neuritis and  iritis in reactions often need steroids. But particular in chronic ENL I think steroids should be used cleverly and intermittently.

 

Are there studies comparing GTW with other ways of handling ENL? I have no experience with it and from what I know as a immunosuppressant it is not strong. Hence you advice it as a not first line drug in ENL.

 

Concerning thalidomide as first line drug I have no strong opinion, I usually used steroids, but that has to do with the availability of the drug. Again the Brazilians will have most experience. In the past in Africa I saw most severe ENL in man. Now with the availability in Brazil for man I see most severe and chronic ENL in woman. So thalidomide certainly has a place. I think it even may prevent ENL, when the relative low dose steroids that do not.

 

But as far as I understood the ENL  is in remission.

 

I wish you strength in handling this patient.

 

 

With great regards

 

dr Ben Naafs

 

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com

 

 



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(LML) Thalidomide in treating kidney involvement in ENL

Leprosy Mailing List – December 20,  2013 

Ref.:    (LML)  Thalidomide in treating kidney involvement in ENL

From:  Jingquan Wang,  Zhejiang, China

Dear Pieter,


We have consider the proposal of  Dr Ben Naafs that there could be urinary tract infection and azithromycin 1g daily for 2days  was prescribed, but it did not work and  blood in urine and leukocyturia is still present.

 

Forty five days after the start of thalidomide, a severe headache happened in the patient with a slight high blood pressure. We had to stop thalidomide and a drug named multi-glycosides of triptergium wilfordii hook f (MGTW) which has the effect to control ENL and kidney damage  and recommended by China leprosy control programme, with a dosage of 60 mg daily,  was used to continue the therapy.

 

Now we have treated the patient as such for two weeks and still no response in  mitigating the kidney involvement. I think maybe we have to use prednison to treat the patient despite of her  slow virus hepatitis B infection. The iridocyclitis of the patient is well controlled with cortisone eye drops and atropine eye gel during the initial several days.

 

In my view, I think short course predinison is imperative in severe ENL cases, especially for those cases with neuritis, iritis and kidney involvement. For severe cases or chronic cases,  drugs such as thalidomide, multi-glycosides of triptergium wilfordii hook f (MGTW), B663(which is not available in China) should not be chosen as the first line drug in controlling ENL.

Best regards.

Jingquan Wang

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com

 



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Thursday, December 19, 2013

Heiser Program for Research in Leprosy 2014

Leprosy Mailing List – December 19,  2013 

Ref.:    (LML) Program for Research in Leprosy 2014

From:  Patrick Brennan, Fort Collins, Colorado State, USA

 

Dear Pieter,

Attached is the RFP for 2014 issued by The Heiser Program for Research in Leprosy administered by the New York Community Trust.

The contact person there is Len McNally (lm@nyct-cfi.org). He can supply the required forms for applications.

 

Thank you,

 

Patrick Brennan

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com

 



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Wednesday, December 18, 2013

(LML) Thalidomide in treating kidney involvement in ENL

Leprosy Mailing List – December 18,  2013 

Ref.:   (LML)  Thalidomide in treating kidney involvement in ENL

From:  Ben Naafs, Munnekesburen, the Netherlands

 

 

Dear Pieter,

 

 

I would like to thank Dr. Jingquan Wang for his interesting question about the use of Thalidomide in treating kidney involvement in ENL (LML, December 16, 2013). ENL is a stressful situation, the patient is really severely ill; proteinuria, albuminuria, is a frequent symptom is this condition. Treatment of the ENL reverses this situation, the patient becomes better and the proteinuria disappears. This is independent of the way the ENL is being treated and happens with spontaneous evolution too. When proteinuria remains, permanent damage may have happened or there is still another stressful condition.

                                  

When after the proteinuria disappears, blood and leukocytosis remains, I think for example of an urinary tract infection, particular in women. This could also has been the triggering factor for the ENL.

 

ENL in all other organs can be treated with thalidomide too. Sometimes, however, in case of neuritis or iritis steroids may be advisable. Thalidomide is widely used in Brazil and they should have a lot of experience with internal organs involvement in ENL and how to treat.

 

 

With kind regards,

 

Dr Ben Naafs

 

 

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com



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(LML) Taking and processing of Slit Skin Smears and Staining of Biopsies

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Leprosy Mailing List – December 18,  2013 

Ref.:    (LML) Taking and processing of Slit Skin Smears and Staining of Biopsies

From:  Jaison Barreto, ILSL Bauru, São Paulo, Brazil

Dear Pieter,

 

Why everybody does believe that a patient with less than 6 lesions has PB leprosy? It is easy to answer. I see problems with taking of skin slit skin smears almost every day. Material from lesions is often difficult to collect, and in many instances lesions are not represented in the slit skin smears, i.e., only material from ear lobes and knees are collected. The person who collects the material (laboratory technician) is not the same one that does the dermatological examination, and, of course, this technician is not allowed to ask the patient to take of the clothes, in order to perform the collection of the lesions; common sites are buttocks, thighs and trunk.

 

Moreover, often staining of slit skin smears is performed wrongly. I saw this problem in the state of Mato Grosso do Sul 4 years ago. This Brazilian state was believed to have the best bacilloscopy in Brazil. When we went to the field for direct supervision, with the support of DAHW, we saw that 84% of the municipalities had problems with the techniques (collecting, fixing, dying, de-staining, interpretation, and others).

 

Other problem I saw in the field is that many histopathologal laboratories perform the staining of M. leprae in biopsies wrongly. They just do not know that the resistance to de-staining of carbolfuchsin from M.leprae and other mycobacteria are different. The cell wall of M. leprae is “soft”, and if when the de-paraffinization is performed in pure xylene, the result is a thin layer to be stained, and when 3% alcohol-acid is used to de-stain carbolfuchsin, instead of 1%, a catastrophe occurs: even LL leprosy does not show AFB (see differences of the same material showed in the microphotos enclosed. I personally believe this to have happened in many patients with neural sarcoidosis described in literature.

 

 

Best regards,

 

 

Jaison

LML - S Deepak, B Naafs, S Noto and P Schreuder

LML blog link: http://leprosymailinglist.blogspot.it/

Contact: Dr Pieter Schreuder << editorlml@gmail.com

 

 



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