Printer Friendly

Management of chronic neuritis with a combination regimen of lower doses prednisolone and methotrexate: a brief report.

Six hundred and seventy new cases had been enrolled during the last 10 years (2004-2013) in one of our leprosy clinics. Among them 300 (44.77%) patients experienced leprosy complications. Of them 137 (45.66%) had neuritis. All were treated with prednisolone for 4-6 months. All but 25 (18.24%) responded well. They showed protracted response to multiple interrupted prednisolone courses causing patients to suffer for years. And this is the frequency of chronic neuritis prevailing across our country.

A case controlled blinded study had not found prednisolone effective in treating chronic neuritis and the authors preferred spontaneous healing as one of the management strategies for them. (1) Unfortunately, this is neither ethical nor appreciable by the patients in the field situation.

We have seen resolution of ENL (2) and RRs associated (3) neuritis with a combination therapy of prednisolone and methotrexate. We treated three patients with same combination for one year. They had been suffering from chronic neuritis with functional impairment for 3 to 10 years. They had two-four 4-6 months prednisolone courses and finally were on and off self-administered prednisolone for years (Table 1).

A base line record was made by body chart, sensory test with nylon monofilament, voluntary muscle test (vmt), slit skin smear test (sss), and routine blood/urine/stool tests. Then quarterly nerve palpation together with sensory and vmt test, liver function test and blood routine test were done. Yearly sss tests were done during treatment and the subsequent follow up period.

We put them on prednisolone, 20 mg/day (their maintenance dose) as an initial dose and tapered 5 mg quarterly to end the course in 12 months. Methotrexate, 2.5 mg, 12-hourly, 3 doses weekly for the same period of time. We asked them to report quarterly during treatment and 6-monthly during surveillance.

Neural pain and tenderness went off after 9 months' treatment. Change in nerve swelling, consistency and functional regain were being noticed during first through fourth quarters (Table 2).

Finally there was complete and permanent resolution of neuritis with good sensory and some motor functional recovery even in these old cases. There was no recurrence of neuritis and worsening of achieved functions during 1 year surveillance period.

All patients experienced self-limiting mild gastric pain and slight weight gain from prednisolone. There were no side-effects from methotrexate.

Infection of Schwann cells with M. leprae results in demyelination, axonal dysfunction and immunological granulomatous reaction in the nerve. (4) At its height, episodic leprosy reaction associated inflammation worsened the nerve injury by direct axonal damage and compromised circulation from intra-neural edema. (5)

Prednisolone has the potential to reduce intra-neural edema and suppress the T cell-driven inflammatory response to M. leprae antigens. Methotrexate has the potential to reduce pro-inflammatory cytokines, decrease the expression of Th1 cytokines, increase the expression of anti-inflammatory Th2 cytokines, supression of lymphocyte proliferation, neutrophil chemotaxis and adherence, and reduce serum immunoglobulin. (6) Perhaps these were the mechanisms for bringing beneficial effects in our patients, though the exact mechanism is not known.

In conclusion, a combination of lower doses prednisolone and methotrexate was found effective and safe in treating prednisolone resistant chronic neuritis and individualised prolonged duration (till complete and permanent resolution of inflammation) is important. Case controlled blinded study is welcomed.

References

(1) Richardus JH, Withington SG, Anderson AM et al. Treatment with corticosteroids of long standing nerve function impairment in leprosy: a randomised controlled trial (TRIPOD 3). Lepr Rev, 2003; 74: 311-318.

(2) Hossain D. Using methotrexate to treat patients with ENL unresponsive to steroid and clofazimine: A report on 9 patients. Lepr Rev, 2013; 84: 105-112.

(3) Hossain D. Management of chronic neuritis with an extended and continuous course of prednisolone and methotrexate: a case report. American Journal of Clinical and Experimental Medicine, 2014; 2: 171-174.

(4) Scollard DM. The biology of nerve injury in leprosy. Lepr Rev, 2008; 79: 242-253.

(5) Britton WJ. The management of leprosy reversal reactions. Lepr Rev, 1998; 69: 225-234.

(6) Swierkot J, Szechinski J. Methotrexate in rheumatoid arthritis. Pharmacol Rep, 2006; 58: 473-492.

DELWAR HOSSAIN, University of Science and Technology Chittagong (USTC), Bangladesh

Accepted for publication 6 November 2015

Correspondence to: Delwar Hossain, Department of Dermatology and Venereology, University of Science and Technology Chittagong (USTC), Foy's lake, Khulsi, Chittagong, Bangladesh, GPO Box-1079 (Tel: + 01771318078; e-mail: delwar_ustc@yahoo.co.uk)
Table 1. Demography of study patients

Salient features                     Received treatment

Patient-1

A female of 23 years had multiple    Combination therapy of
  anesthetic patches, multiple         prednisolone and methotrexate
  enlarged nerves with sensory         for 12 months.
  and motor functions loss for
  last six months. Her slit skin
  smear (sss) test was negative.
Registered in January, 2008 as BT
  leprosy and received MDT-MB
  that she completed in due time.
January, 2009 to March, 2010 she
  received two 4-months courses
  of prednisolone for new
  development of post treatement
  neuritis in right ulnar nerve
  with functional loss. That was
  incompletely resolved.
June-September, 2010, she
  received third 4-monthly course
  of prednisolone for recently
  developed ENL reaction at the
  top of mild neuritic pain in
  ulnar nerve.
December, 2010 to September,
  2011, she received second
  MDT-MB course for second ENL
  reaction and SSS test
  positivity. Then next six
  months she was on
  self-administered prednisolone
  for mild neuritis in ulnar
  nerve.
At our enrollment (March, 2012),
  she had hugely enlarged and
  severely painful-tender right
  unnar nerve with recent motor,
  sensory and autonomic functions
  loss.

Patient-2

A male of 55 years had anesthetic    Combination therapy of
  patches, anesthesia and              prednisolone and methotrexate
  multiple ulcers in left foot         for 12 months.
  and mild paiful-tender left
  common peroneal nerve for last
  six years. His sss test was
  negative.
Registered in August, 2008 as BT
  leprosy and received MDT-MB and
  two 6-months courses of
  prednesolone that he completed
  in due time. He was released
  from treatment with tolerable
  mild neuritc pain.
At our enrollment (June, 2012),
  he had severely enlarged and
  painful-tender left common
  peroneal nerve with recent
  worsening of sensation along
  left lower antero-medial leg
  and medial dorsal foot. There
  was cramps in the leg muscles.

Patient-3

A girl of 13 years had anesthesia    Combination therapy of
  and clawing of right hand with       prednisolone and methotrexate
  enlarged, moderately painful         for 12 months.
  and tender ulnar nerve for one
  year duration. Her sss test was
  negative.
Registered in September, 2010 as
  BT leprosy, received MDT-MB
  with two 4-months course of
  prednisolone that she completed
  in due time. She was released
  from treatment with active mild
  neuritis in right ulnar nerve.
  She was on and off
  self-administered prednisolone
  since then.
At our enrollment (August, 2012),
  she had severely enlarged,
  hard, severely painful-tender
  right ulnar nerve with recent
  worsening of palmar anesthesia,
  dryness and muscle weekness.

Salient features                     Outcome

Patient-1

A female of 23 years had multiple    Permanent resolution of neuritis
  anesthetic patches, multiple         with recovery of sensory and
  enlarged nerves with sensory         some motor functions.
  and motor functions loss for
  last six months. Her slit skin
  smear (sss) test was negative.
Registered in January, 2008 as BT    The outcome was persistent during
  leprosy and received MDT-MB          one year follow up period.
  that she completed in due time.
January, 2009 to March, 2010 she
  received two 4-months courses
  of prednisolone for new
  development of post treatement
  neuritis in right ulnar nerve
  with functional loss. That was
  incompletely resolved.
June-September, 2010, she
  received third 4-monthly course
  of prednisolone for recently
  developed ENL reaction at the
  top of mild neuritic pain in
  ulnar nerve.
December, 2010 to September,
  2011, she received second
  MDT-MB course for second ENL
  reaction and SSS test
  positivity. Then next six
  months she was on
  self-administered prednisolone
  for mild neuritis in ulnar
  nerve.
At our enrollment (March, 2012),
  she had hugely enlarged and
  severely painful-tender right
  unnar nerve with recent motor,
  sensory and autonomic functions
  loss.

Patient-2

A male of 55 years had anesthetic    Permanent resolution of neuritis
  patches, anesthesia and              with recovery of sensory
  multiple ulcers in left foot         function.
  and mild paiful-tender left
  common peroneal nerve for last
  six years. His sss test was
  negative.
Registered in August, 2008 as BT     The outcome was persistent during
  leprosy and received MDT-MB and      one year follow up period.
  two 6-months courses of
  prednesolone that he completed
  in due time. He was released
  from treatment with tolerable
  mild neuritc pain.
At our enrollment (June, 2012),
  he had severely enlarged and
  painful-tender left common
  peroneal nerve with recent
  worsening of sensation along
  left lower antero-medial leg
  and medial dorsal foot. There
  was cramps in the leg muscles.

Patient-3

A girl of 13 years had anesthesia    Permanent resolution of neuritis
  and clawing of right hand with       with recovery of sensory and
  enlarged, moderately painful         some motor function.
  and tender ulnar nerve for one
  year duration. Her sss test was
  negative.
Registered in September, 2010 as     The outcome was persistent during
  BT leprosy, received MDT-MB          one year follow up period.
  with two 4-months course of
  prednisolone that she completed
  in due time. She was released
  from treatment with active mild
  neuritis in right ulnar nerve.
  She was on and off
  self-administered prednisolone
  since then.
At our enrollment (August, 2012),
  she had severely enlarged,
  hard, severely painful-tender
  right ulnar nerve with recent
  worsening of palmar anesthesia,
  dryness and muscle weekness.

Table 2. Assessing nerve and its function during our anti-neuritic
treatment

Parameters    Patient                            1st quarter

Pain          p-1                                Severe
              P-2                                Severe
              P-3                                Severe
Tenderness    P-1                                Severe
              P-2                                Severe
              P-3                                Severe
Enlargement   P-1                                Severe
              P-2                                Severe
              P-3                                Severe
Consistency   P-1                                Hard
              P-2                                Hard
              P-3                                Hard
Function      P-1       Palmar sensation         Anesthesia
                        Abd digit minimi         P
                        Palmar interossei, 1-3   P
                        Dorsal interossei, 1-4   P
                        Extensor poll longus     W2
              P-2       Sensation of leg and     Anesthesia
                          dorsal foot
              P-3       Palmar sensation         Anesthesia
                        Abd digit minimi         P
                        Palmar interossei, 1-3   P
                        Dorsal interossei, 1-4   P
                        Extensor poll longus     W1

Parameters    Patient                            2nd quarter

Pain          p-1                                Moderate
              P-2                                Moderate
              P-3                                Moderate
Tenderness    P-1                                Moderate
              P-2                                Moderate
              P-3                                Moderate
Enlargement   P-1                                Severe
              P-2                                Severe
              P-3                                Severe
Consistency   P-1                                Firmer
              P-2                                Firmer
              P-3                                Firmer
Function      P-1       Palmar sensation         Anesthesia
                        Abd digit minimi         P
                        Palmar interossei, 1-3   P
                        Dorsal interossei, 1-4   P
                        Extensor poll longus     W2
              P-2       Sensation of leg and     Anesthesia
                          dorsal foot
              P-3       Palmar sensation         Anesthesia
                        Abd digit minimi         P
                        Palmar interossei, 1-3   P
                        Dorsal interossei, 1-4   P
                        Extensor poll longus     W1

Parameters    Patient                            3rd quarter

Pain          p-1                                Mild
              P-2                                Mild
              P-3                                Mild
Tenderness    P-1                                Mild
              P-2                                Mild
              P-3                                Mild
Enlargement   P-1                                Moderate
              P-2                                Moderate
              P-3                                Moderate
Consistency   P-1                                Firm
              P-2                                Firm
              P-3                                Firm
Function      P-1       Palmar sensation         Partial loss
                        Abd digit minimi         W1
                        Palmar interossei, 1-3   W1
                        Dorsal interossei, 1-4   W1
                        Extensor poll longus     W3
              P-2       Sensation of leg and     Partial loss
                          dorsal foot
              P-3       Palmar sensation         Partial loss
                        Abd digit minimi         P
                        Palmar interossei, 1-3   W1
                        Dorsal interossei, 1-4   W1
                        Extensor poll longus     W2

Parameters    Patient                            4th quarter

Pain          p-1                                No pain
              P-2                                No pain
              P-3                                No pain
Tenderness    P-1                                Normal
              P-2                                Normal
              P-3                                Normal
Enlargement   P-1                                Moderate
              P-2                                Mild
              P-3                                Moderate
Consistency   P-1                                Firm
              P-2                                Firm
              P-3                                Firm
Function      P-1       Palmar sensation         Regained sensation
                        Abd digit minimi         W1
                        Palmar interossei, 1-3   W2
                        Dorsal interossei, 1-4   W2
                        Extensor poll longus     W4
              P-2       Sensation of leg and     Regained sensation
                          dorsal foot
              P-3       Palmar sensation         Regained sensation
                        Abd digit minimi         P
                        Palmar interossei, 1-3   W2
                        Dorsal interossei, 1-4   W2
                        Extensor poll longus     W3

Note:

Pain: Mild pain-normal daily functions with feeling pain at movement;
moderate pain-normal daily functions could be done with difficulty
and severe pain-impairment/limitation in daily functions.

Tenderness: Mild tenderness-eye blenching due to feeling of pain in
nerve at palpation; moderate tenderness-eye blenching and change in
facial expression due to feeling of pain in nerve at palpation and
severe tenderness-uttering oh! Ah! and an attempt to withdraw limb
at palpation of nerve.

Size: Mild enlargement-double the normal size; moderate
enlargement-tripple the normal size; severe/huge enlargement-four or
more times enlargement than normal size.

Muscle paralysis: P-paralysis;W1-no movement but palpable contraction
of muscle; W2-movementbut not full range; W3-full range of movement
without resistance and W4-full range of movement against some
resistance.
COPYRIGHT 2016 British Leprosy Relief Association
No portion of this article can be reproduced without the express written permission from the copyright holder.
Copyright 2016 Gale, Cengage Learning. All rights reserved.

Article Details
Printer friendly Cite/link Email Feedback
Author:Hossain, Delwar
Publication:Leprosy Review
Article Type:Letter to the editor
Date:Mar 1, 2016
Words:1995
Previous Article:Prospective analytical study of assessment of off loading by Total Contact Cast in treatment of non healing plantar ulcers in anaesthetic foot.
Next Article:Investment case concepts in leprosy elimination: a systematic review.
Topics:

Terms of use | Privacy policy | Copyright © 2019 Farlex, Inc. | Feedback | For webmasters