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 Table of Contents  
CASE REPORT
Year : 2014  |  Volume : 8  |  Issue : 2  |  Page : 100-106

Therapeutic effect of Mercurius solubilis on immune status of a borderline leprosy case


1 Institute of Health Studies and Rehabilitation, Durgapur, West Bengal, India
2 Department of Pathology, All India Institute of Medical Sciences, New Delhi, India
3 Rajendra Memorial Institute of Medical Sciences, Patna, Bihar, India
4 Specialist, Diagnostic Pathology, Regional Disease Diagnostic Laboratory (ER) IAH and VB, Government of West Bengal, Kolkata, West Bengal, India

Date of Submission12-Jun-2013
Date of Acceptance17-Jun-2014
Date of Web Publication30-Jun-2014

Correspondence Address:
Dr. Dhruba Chakraborty
Institute of Health Studies and Rehabilitation, (Society for Welfare of the Handicapped Persons), 27 Tagore Avenue, Durgapur - 713 204, West Bengal
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-7168.135643

Clinical trial registration CTRI/2008/091/000080

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  Abstract 

A Borderline Lepromatous (BL) leprosy case was treated with Mercurius solubilis, a homoeopathic medicine for two years. The clinical, immunological and histological assessment of the patient before and after treatment was recorded. The patient showed appreciable improvement in clinical signs and symptoms. Lesions on the skin almost disappeared; no swelling of hand and feet was noted along with disappearance of infiltration on eye brows. Nodular lesions on both the ear lobes diminished remarkably. Regain of sensation to touch, pain and pressure were noted and their test responses were normal. Slit skin smears were negative from all sites with 0 Bacteriological Index [BI] which was positive for acid fast bacilli [AFB] with an average of 4+ BI before treatment. Histologic study revealed absence of granuloma in dermis except the presence of occasional clusters of lymphocytes. Lepromin reaction which was negative before treatment was positive with 14 mm after 2 years of treatment. Estimation of different cytokines after completion of treatment showed appreciable changes with remarkable reduction in the levels of proinflammatory cytokines (IFN and TNF).

Keywords: Bacterial index, Cytokines, Leprosy, Mercurius solubilis


How to cite this article:
Chakraborty D, Dinda AK, Sengupta U, Das P, Chakraborty T, Sengupta J. Therapeutic effect of Mercurius solubilis on immune status of a borderline leprosy case. Indian J Res Homoeopathy 2014;8:100-6

How to cite this URL:
Chakraborty D, Dinda AK, Sengupta U, Das P, Chakraborty T, Sengupta J. Therapeutic effect of Mercurius solubilis on immune status of a borderline leprosy case. Indian J Res Homoeopathy [serial online] 2014 [cited 2019 Nov 19];8:100-6. Available from: http://www.ijrh.org/text.asp?2014/8/2/100/135643


  Introduction Top


Leprosy is a chronic infectious disease caused by Mycobacterium leprae (M. leprae) affecting the peripheral nerves leading to impairment of their motor, sensory or autonomic function. [1],[2] The disease is characterized by a spectrum of clinical manifestations determined by the host immune response to M. leprae. [3] While at the Lepromatous (LL) pole, the hosts lack effective Cell-Mediated Immunity (CMI) to M. leprae allowing bacilli for unlimited proliferation, at the Tuberculoid (TT) pole, the hosts exhibit a strong CMI to M. leprae leading to elimination of mycobacteria. Borderline leprosy patients who lie between the tuberculoid and lepromatous poles are immunologically unstable. At least 30% of borderline patients experience episodes of up-regulation of M. Leprae specific CMI with acute inflammation of existing skin lesions and nerves, and is termed as Type 1 reaction (T1R) or reversal reaction. [4] These episodes are often recurrent with increased CMI to M. leprae resulting in the elimination of bacilli leading to immunological upgradation of the patient towards a more tuberculoid type of disease. Most of the time, T1R is accompanied by local tissue damage, acute inflammation of pre-existing skin lesions and acute neuritis. [5] The neuritis may often become rapid and severe leading to permanent nerve damage. World Health Organization (WHO) has recommended Multi Drug Therapy (MDT) regimen with combination of rifampicin, clofazimine and dapsone for treatment of leprosy. If a reversal reaction is found to occur in the course of disease progression in borderline forms (Borderline Tuberculoid, BT; Borderline, BB; and Borderline Lepromatous, BL), steroid (prednisolone) is the only drug of choice along with MDT. Prednisolone, known to suppress CMI and inflammatory processes, leads to reduction in compression around the affected nerves, inhibiting scar formation in the nerve and thus helps in the recovery of nerve functions in T1R reaction. Thus, steroids and dapsone used for treatment of leprosy have no potential to up-regulate, rather these have the role to play in down-regulation of the immune status of the host. [6] Levels of TNF-α and IFN-γ are significantly raised in paucibacillary cases, whereas IL-10 is found to be increased in multibacillary cases. In multibacillary cases, levels of IL-10 were found to decrease after one year of MDT. Thus, serum cytokine estimation may have a significant role in classifying various forms of leprosy and can be used to monitor therapy. [7],[8]

In this communication, a case of BL leprosy treated with Mercurius solubilis in 200 potency, with detailed follow up observations recorded after a period of two years has been presented.


  Case Report Top


A male patient of 56 years reported to the OPD of the Institute with multiple hypoaesthetic, hypopigmented macular lesions on the face [Figure 1]a and b and on other parts of the body.
Figure 1: (a) Before treatment infiltration present on both eye brows and macular patch present on face; (b) Active nodules present on ear lobe

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Nodular type of lesions on the whole body and both the ear lobes were present. Swelling of both hands and feet with infiltration in eye brows was also noted along with complaint of pain in the nasal septum. As a whole, the signs and symptoms were expressed in the form of bilateral symmetrical presentation. Both ulnar nerves as well as peroneal and tibial nerves were thickened and tender.

On the day of registration, slit skin smears taken from both the ear lobes and both the hands and legs were positive for AFB with an average BI of 4+. Skin biopsies were taken from the edge of lesions before the onset and at the end of the treatment. The skin biopsies were fixed in 10% buffered formal-saline solution and processed for paraffin sectioning at 5/u thickness following standard techniques and stained with routine haematoxylin and eosin as well as stained for AFB. Lepromin testing was carried out with standardized Dharmendra antigen which evokes both early (48 to 72 hours) and late (3 to 4 weeks) skin reaction. [9] Venous blood sample (5 ml) was taken for estimation of interleukins (IL; IL-2, IL-4, IL-10) and other pro-inflammatory cytokines like Interferon-gamma (IFN-γ) and Tumour Necrosis Factor-alpha (TNF-α) employing standard enzyme-linked immunosorbent assay (ELISA) Kits.

The sensory nerve function testing of the palms of the hands and soles of the feet was carried out using ball-point pen as described by Jean Watson at twelve standard points on each palm and on eleven points on the soles. [10] On the palm, five points were taken as supplied by the ulnar nerve and seven for the median nerve.

Touch sensation was tested using a standard set of coloured Semmes-Weinstein monofilaments. The monofilaments used were 200mg, 2g, 4g, 10g and 300g. Normal reference values were 200mg for hand and 10g for foot. The sensory test carried out on hands and feet showed complete loss of sensation to touch, pressure and pain.

Histopathological findings before treatment revealed normal epidermis. Dermis showed involvement of nerve bundles with perineuritis, endoneuritis and formation of granulomatous lesions in the nerves with foam cells. Multiple granulomas with foam cells were noted in the dermis. These features were suggestive of BL type of leprosy [Figure 2]a. The stain for AFB was positive.
Figure 2: (a) Photomicrograph of the pretreatment skin biopsy showing normal epidermis, infiltration of dermis with histiocytes and lymphocytes. There is nerve involvement with perineiritis, endoneuritis and formation of granulomatous lesions in the nerve cell with foam cells. x400; (b) Photomicrograph of the post treatment skin biopsy showing unremarkable epidermise. There are few aggregates of lymphocytes in the dermis. No granuloma or foam cell is identified. x400

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Before treatment, lepromin testing showed negative reaction [Figure 3]a. On the basis of clinical signs and histopathology, the case was confirmed as a case of BL leprosy.
Figure 3: (a) Pretreatment lepromin (0mm) reaction after 3 weeks

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The patient was subjected to detailed case taking which revealed,

A. Particular symptoms

Head -
Headache of throbbing nature which aggravated in the heat, when exposed to sun and in a closed room

Eye - Low vision at night

Nose - Pain at the root of the nose with history of nasal bleeding

Mouth and Tongue - Moist, flabby, tendency of ulcer formation, profuse salivation, saliva was viscid and foetid, gums were painful with bleeding and with pain at night

Face - Swelling of face with reddish lesions on face and forehead

Stomach - Occasional colicky pain worse at night

Abdomen - Occasional pain in lower abdomen in summer with history of dysentery

Stool - Occasional dysenteric stool with occasional bleeding per rectum; slimy stool with mucus

Urine - Occasional burning during micturition.

Extremities (upper ): Anaesthetic, hypopigmented macular patch present on hands, neuralgic pain in both ulnar nerves, swelling of both the hands with stiffness.

Extremities (lower): Swelling of both the feet with tendency of ulcer formation, neuralgic pain greater at night. Thickness of tibial and peroneal nerves was present.

Skin : Presence of anaesthesia in lesional areas. In general, skin was moist but dry in lesional areas without any sweating. Tendency of ulcer formation and little injury led to suppuration.

Nervous system : Both ulnar nerves as well as peroneal and tibial nerves were thickened and painful. Pain aggravated at night and during cold season, ameliorated by rest and pressure. Bones of hand and feet were very sensitive and painful and mild pressure led to pain.

B. General symptoms

Mental symptoms
: Melancholy, hopelessness, lack of confidence, depression, anxiety at night. Anxious and fearful. Restlessness and weak memory. When asked a question, he was unable to reply properly.

Sleep - Complained of disturbed sleep, sleepless night.

Dreams : Bad and violent dreams at night, especially dreams of dead persons and murders .

Mouth:
Moist mouth and salivation

Thirst : Profuse

Tongue: Thick, moist coating, flabby, teeth-indented. Ulceration of tongue

Sweat : Profuse sweating day and night without relief. The complaint increased when exposed to sun in summer. Offensive sweat caused discomfort < from least exertion

Appetite: Normal.

Liking : Nothing specific.

Response to heat and cold - High sensitivity to extreme heat and cold, all complaints aggravated in summer as well as in winter, preferred moderate climate and temperature, felt better under shade

General Agg
. - All the complaints aggravated at night

Physical condition - Weak, lean, thin and emaciated.

The past history of the patient did not reveal any sexual illness or any drug or mercurial poisoning whereas skin disease with suppression was reported by the patient. It was also revealed further that the patient had close contact with other leprosy patients earlier.

The family history revealed that both the parents died long ago and father was suffering from leprosy. Four other family members were also found to be affected with leprosy.

Selection of Medicine

After thorough clinical examination and detailed case study, the selection of medicine was done according to William Boericke [11] and Kent's repertory. [12]

Based on Accumulated Similar Symptom (ASS), the selection of medicine, Merc. sol. in 200 potency was made and one dose weekly was given for two years as described by Chakraborty et al. [13]

Post Treatment Evaluation

Clinical examination after six months (17.09.2008) revealed appreciable improvement in clinical signs and symptoms. Patches were found to have disappeared on both the extremities (upper and lower) and sensations were regained. The most remarkable sign was the disappearance of swelling of lower extremities and infiltration on eye brows [Figure 4]a.
Figure 4: (a) After treatment no infiltration and macular patch seen on face. Appearance of face looks normal; (b) After treatment ear lobe looks inactive, nodules are very small and dry

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No signs of psychological depression was recorded in the appearance with complete absence of patches on the face. No swelling was recorded. The only particular symptom, low vision of the eye was reported by the patient.

Nodular lesions on both the ear lobes diminished remarkably [Figure 4]b. After two years on 23.03.2010, clinical sign showed regain of sensation to touch, pain and pressure and their test responses were normal.

Pathological and Immunological Investigations

After one year of treatment, slit skin smears were positive for AFB and BI was 1.8, and after two years of treatment, slit skin smears were negative from all sites with 0 BI. After one year of treatment (18.03.2009), the numbers and sizes of granulomas reduced with lymphocytic infiltration. After two years of treatment (23.03.2010), no granuloma was noted in the dermis except for the presence of occasional clusters of lymphocytes [Figure 2]b. The stain for AFB was negative.

Estimation of different cytokines (IL2, IL4, IL10, IFNγ and TNFα) showed appreciable changes in post treated cases [Table 1].
Table 1: Criteria for selection of medicine

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At the end of two years, the only particular symptom, low vision of the eye was reported by the patient. No signs of psychological depression were recorded with complete absence of patches on the face. No swelling was noticed.

General symptoms as recorded:

  • Mental symptoms: Very confident. No anxiety and depression was reported
  • Thirst: Normal
  • Sweat: Normal
  • Appetite: Normal
  • Liking and Aversion: No significant change
  • Response to heat and cold: Normal response was noted
  • Sleep and Dreams: No disturbed sleep was reported
  • Physical condition: Good health.


During the period under treatment no acute illness was reported by the patient.

After completion of two years, the patient was subjected to follow up for another six months which did not reveal any significant change in clinical manifestation.


  Discussion Top


This case study reports successful treatment of a case of BL leprosy with two years of homoeopathic treatment. All lesions disappeared without any episode of reaction. The slit skin smears were negative with 0 BI . The nerve function impairment of hands and feet got reversed with complete regain of sensation. The efficacy of the single homoeopathic medicine, Mercurius solubilis in this case is considered remarkable because of its ability to influence host immune response.

The immune system of the host gets adversely affected in leprosy posing major therapeutic challenge to the researchers. After completion of WHO recommended MDT for 6 months in paucibacillary leprosy and one year in multibacillary leprosy, clinically, most of the patients do not feel themselves as cured because of the existence of their lesions and loss of sensation even after completion of MDT. Even the immune status of the lepromatous type of leprosy remains unaltered. Furthermore, presence of viable M. leprae has been convincingly detected from such lesions after completion of MDT. [14] Out of the three drugs included in MDT, dapsone and clofazemine are known bacteriostatic drugs, probably due to which the affected person does not get rid of the residual effects of the disease, and dapsone has also been found to lower the CMI status of the patients. [15],[16] However, rifampicin is known to kill 99.9% of M. leprae within a month's time. [17] In spite of this, relapses are not uncommon among the treated cases.

Therefore, it may be concluded that the present homoeopathic treatment with Merc. sol. in leprosy cases where neuritis has already developed, may save the patients from the grave consequences of nerve function impairment and development of deformity. The medicine in this case was found to be effective in reducing the load of M. leprare as was evident from the fall of BI from 4+ to 0 within two years. Whether this remarkable reduction in BI is due to the direct effect of the drug on M. leprae or due to the immunomodulation of the host, remains to be worked out. The lepromin response recorded after two years indicated that this medicine has up-regulated the immune status of the host which is not observed with MDT. This treatment specifically brought down the levels of proinflammatory cytokines (IFNγ and TNFα) and increased the levels of suppressive cytokine IL-10 and IL-4. IL-10 is known to down-regulate IFNγ and TNFα. [18] IL-4 down-regulation appears to influence the B cells for reduced production of antibodies. [19] The difference in cytokine levels of blood before and after treatment is also suggestive of some effect of the drug in modulating the mechanism on the host immune system, which needs to be studied. Studies revealed that treatment with multi drug has been found to cause a reduction in serum cytokines correlated with a reduction in the bacterial burden [7],[8] and the medicine used in this case is equally effective in bringing down serum cytokines and bacterial burden.


  Conclusion Top


MDT is used as an important instrument to reduce the burden of active cases of leprosy. However, affected people remain at risk of neuropathy resulting from immunological reactions caused by M. leprae antigens during and even after successful anti-leprosy treatment. In National Leprosy Eradication Programme (NLEP), there is no effective treatment suggested for prevention of disability caused by neuropathy, except the use of prednisolone for nerve function impairments that takes place during the period of MDT treatment.

Therefore, at this crucial juncture of leprosy elimination, this alternative therapeutic approach may be a justifiable proposition and would be of great help to treat the leprosy patients with nerve function impairments thus fulfilling the ultimate goal of WHO. [20]


  Acknowledgements Top


This work is a part of a project 'Role of homoeopathic medicines in up-regulation of host immunity using leprosy disease model' funded by Ministry of Health and Family Welfare, Government of India. The authors are thankful to the Secretary, Department of AYUSH, Ministry of Health and Family Welfare, Government of India for providing funds for the project. The authors are grateful to the Director General, Central Council for Research in Homoeopathy for providing technical guidance.

 
  References Top

1.Van Brakel WH, Khawas IB. Nerve damage in leprosy: An epidemiological and clinical study of 396 patients in West Nepal-Part 1. Definitions, methods and frequencies. Lepr Rev 1994;65:204-21.  Back to cited text no. 1
    
2.Job CK. Nerve damage in leprosy. Int J Lepr Other Mycobact Dis 1989;57:532-9.  Back to cited text no. 2
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3.Ridley DS, Jopling WH. Classification of leprosy according to immunity: A five-group system. Int J Lepr Other Mycobact Dis 1966;34:255-73.  Back to cited text no. 3
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4.Lienhardt C, Fine PE. Type 1 reaction, neuritis and disability in leprosy. What is the current epidemiological situation? Lepr Rev 1994;65:9-33.  Back to cited text no. 4
    
5.Ridley DS, Job CK. The pathology of leprosy. In: Hastings RC, editor, Leprosy. Edinburgh: Churchill Livingstone; 1985. p. 100-33.  Back to cited text no. 5
    
6.Naafs B. Bangkok Workshop on Leprosy Research. Treatment of reactions and nerve damage. Int J Lepr 1996;64:S21-8.  Back to cited text no. 6
    
7.Moubasher AD, Kamel NA, Zedan H, Raheem DD. Cytokines in leprosy, II. Effect of treatment on serum cytokines in leprosy. Int J Dermatol 1998;37:741-6.  Back to cited text no. 7
    
8.Madan NK, Agarwal K, Chander R. Serum cytokine profile in leprosy and its correlation with clinico-histopathological profile. Lepr Rev 2011;82:371-82.  Back to cited text no. 8
    
9.Watson JM. Essential action to minimize disability in leprosy patients. London: The Leprosy Mission International; 1988.  Back to cited text no. 9
    
10.Sengupta U, Ramu G, Desikan KV. Assessment of Dharmendra antigen II. Standardization of the antigens. Lepr India 1979;51:316-22.  Back to cited text no. 10
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11.Kent JT. Reperatory of the Homoeopathic Materia Medica. New Delhi: Indian Publishing Co; 1978. p. 72, 73, 418, 633, 1240, 1241, 1252, 1253, 1300, 1303.  Back to cited text no. 11
    
12.Willium B. Pocket Manual of Homoeopathic Meteria Medica. 9 th ed. Seth Dey and Co, Calcutta; 1976. p. 327,433, 433,752, 916, 969.  Back to cited text no. 12
    
13.Chakraborty D, Chakraborty T, Das S, Sengupta J. A randomized double blind clinical trial of a homoeopathic medicine in the treatment of traphic ulcer and neuropathy in leprosy. Indian J Res Homeopath 2009;3:54-64.  Back to cited text no. 13
    
14.Shetty VP, Suchitra K, Uplekar MW, Antia NH. Persistence of Mycobacterium leprae in the peripheral as compared to the skin of multidrug- treated leprosy patient. Lepr Rev 1992;63:329-6.  Back to cited text no. 14
    
15.Sengupta U, Ghei SK, Venkatesan K, Bharadwaj VP. In vivo effect of DDS on phytohaemaglutinin (PHA) induced lymphocyte transformation cultures in normal healthy volunteers. Int J Lepr Other Mycobact Dis 1979;47:167-70.  Back to cited text no. 15
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16.Ramu G, Sengupta U, Desikan KV. Influence of sulphone therapy of lepromin reaction. Lepr Rev 1980;51:207-14.  Back to cited text no. 16
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17.Ellard GA. Chemotherapy of leprosy. Br Med Bull 1988;44:775-90.  Back to cited text no. 17
[PUBMED]    
18.Pestka S, Krause CD, Sarkar D, Walter MR, Shi Y, Fisher B. Interleukin-10 and related cytokines and receptors. Ann Rev Immunol 2004;22:929-79.  Back to cited text no. 18
    
19.Wills-Karp M. Immunologic basis of antigen induced airway hypersensitiveness. Ann Rev Immunol 1999;17:255-81.  Back to cited text no. 19
    
20.World Health Organization. Final push strategy to eliminate leprosy as a public health problem. Questions and answers, WHO Document, 2 nd ed. Geneva: WHO; 2003.  Back to cited text no. 20
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4]
 
 
    Tables

  [Table 1]


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