LEPROSY REACTION IN MYCOBACTERIUM LEPRAE AND MYCOBACTERIUM TUBERCULOSIS CO INFECTION: A CASE REPORT AND LITERATURE REVIEW Corresponding Author and Reprint Request

Abstract

Leprosy reactions are a major cause of nerve damage, morbidity and disability. We present case of lepromatous leprosy with T1R and pulmonary tuberculosis. We reviewed the literature to determine the relationship between co infection and tuberculosis therapy with leprosy reactions. Case report A 69 year old man with type II diabetes mellitus and hypertension presented with numbness of the upper and lower limbs with intermittent swelling of 2 years duration. Physical examination revealed peripheral neuropathy, thickened ulnar nerves and multiple neuropathic ulcers. There were no hypopigmented or hypoaesthetic patches. Slit skin smear morphological index (MI) was 3.7 and bacteriological index (BI) was 0.8. Skin biopsy was not performed as there were no definite skin lesions. Cutaneous tuberculosis is unlikely as there were no skin lesions to suggest tuberculosis. Clinical findings were more suggestive of leprosy due to the presence of peripheral neuropathy, thickened ulnar nerves and neuropathic ulcers. He was diagnosed as lepromatous leprosy with recurrent type 1 leprosy reaction and was treated with Dapsone, Clofazimine and Rifampicin. One month after MDT, he complaint of loss of appetite and 10kg weight loss over 3 months. There was no cough, fever or night sweats. On examination, there were bronchial breath sounds at the right upper zone of the chest and cervical lymphadenopathy. Chest radiograph showed consolidation, fibrosis and cavitations (Figure 1). Cavitations with ground glass and tree in buds appearance were seen on computed tomography. Broncho alveolar lavage culture grew M tuberculosis that was sensitive to all first line anti tuberculosis drugs. Polymerase chain reaction (PCR) isolated M tuberculosis complex. Ethambutol, isoniazid and pyrazinamide were added for treatment of tuberculosis. Dapsone and clofazimine were continued while Rifampicin was changed to daily dose.

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Malaysian Journal of Dermatology
MJD 2016 Dec Vol 3747
Case Report
LEPROSY REACTION IN MYCOBACTERIUM LEPRAE AND
MYCOBACTERIUM TUBERCULOSIS CO INFECTION: A CASE
REPORT AND LITERATURE REVIEW
Jamil A1, Nik Adeeb NN1, Muthupalaniappen L2, Md Nor N1
Corresponding Author and Reprint Request
Dr Adawiyah Jamil, AdvMDerm
Department of Medicine
Universiti Kebangsaan Malaysia Medical Center
Bandar Tun Razak, Cheras,
56000 Kuala Lumpur, Malaysia
Email: adda_jamil@yahoo.com
1 Department of Medicine and
2 Department of Family Medicine,
Universiti Kebangsaan Malaysia Medical Center,
Bandar Tun Razak, Cheras, 56000 Kuala Lumpur
Leprosy reactions are a major cause of nerve
damage, morbidity and disability. We present case
of lepromatous leprosy with T1R and pulmonary
tuberculosis. We reviewed the literature to
determine the relationship between co infection and
tuberculosis therapy with leprosy reactions.
Case report
A 69 year old man with type II diabetes mellitus
and hypertension presented with numbness of the
upper and lower limbs with intermittent swelling
of 2 years duration. Physical examination revealed
peripheral neuropathy, thickened ulnar nerves
and multiple neuropathic ulcers. There were no
hypopigmented or hypoaesthetic patches. Slit
skin smear morphological index (MI) was 3.7 and
bacteriological index (BI) was 0.8. Skin biopsy was
not performed as there were no definite skin lesions.
Cutaneous tuberculosis is unlikely as there were
no skin lesions to suggest tuberculosis. Clinical
findings were more suggestive of leprosy due to the
presence of peripheral neuropathy, thickened ulnar
nerves and neuropathic ulcers. He was diagnosed as
lepromatous leprosy with recurrent type 1 leprosy
reaction and was treated with Dapsone, Clofazimine
and Rifampicin.
One month after MDT, he complaint of loss of
appetite and 10kg weight loss over 3 months. There
was no cough, fever or night sweats. On examination,
there were bronchial breath sounds at the right upper
zone of the chest and cervical lymphadenopathy.
Chest radiograph showed consolidation, fibrosis
and cavitations (Figure 1). Cavitations with ground
glass and tree in buds appearance were seen on
computed tomography. Broncho alveolar lavage
culture grew M tuberculosis that was sensitive to all
first line anti tuberculosis drugs. Polymerase chain
reaction (PCR) isolated M tuberculosis complex.
Ethambutol, isoniazid and pyrazinamide were
added for treatment of tuberculosis. Dapsone and
clofazimine were continued while Rifampicin was
changed to daily dose.
Introduction
Co infection by the two oldest diseases known to
mankind, leprosy and tuberculosis is uncommon.
A systematic review by Rajagopala et al. in 2012
identified 156 cases in the literature1. In India, it is
estimated that 0·019 cases of concomitant infection
would be detected per 100,000 population2. The
pathogenesis of simultaneous Mycobacterium
leprae and Mycobacterium tuberculosis infection
is unclear. Tuberculosis exposure may be protective
against leprosy, as the Bacillus Calmette-Guerin
(BCG) vaccination has been demonstrated to confer
protection against leprosy3.
Leprosy reaction occurs in about 25% of
paucibacillary and 40% of multibacillary leprosy
patients4. Presence of M leprae antigens or DNA in
the skin or nerves, higher expression of mycobacterial
accA3 and hsp18 genes and toll - like receptor (TLR)
gene polymorphism contribute to development of
reactions. Risk factors for type 1 reaction (T1R)
are older age, extensive disease, positive slit skin
smear, household contacts, concurrent infection
and disability at presentation. Risk factors for type
2 reaction (T2R) are bacteriological index (BI) > 4
and lepromatous leprosy.

Malaysian Journal of Dermatology
MJD 2016 Dec Vol 37 48
first infection diagnosed in 8 patients, tuberculosis
was the first diagnosis in 5 patients. Four patients
with leprosy were on prednisolone prior to
developing tuberculosis. Pulmonary tuberculosis
was commonest, other sites reported were the
central nervous system, skin and peritoneum.
There were more T2R compared to T1R. The time
leprosy reaction occurred in relation to diagnosis of
tuberculosis or duration of anti TB was variable and
unpredictable. We were not able to determine the
effect of mycobacterium load and treatment on the
occurrence of reactions as data from the reviewed
articles were limited. In most patients with TB as
the first infection, leprosy reaction occurred at the
presentation of leprosy. However, this maybe an
inaccurate conclusion as the exact time each infection
is acquired cannot be confirmed. Interestingly, drug
resistance was not observed except in one patient
with multi drug resistant tuberculosis including
rifampicin10.
In the presence of suggestive symptoms, acid fast
bacilli isolated from a leprosy or tuberculosis patient
should be confirmed M leprosy or M tuberculosis.
Leprosy reactions may complicate the diagnosis
and treatment of both conditions. It is unlikely that
acquiring tuberculosis infection or tuberculosis
treatment predisposes to leprosy reactions, however
this requires further investigation.
The patient developed another similar episode
of T1R a month after anti TB treatment. He was
treated with prednisolone 30mg daily (0.5mg/kg)
for a month and the dose was tapered off within
2 months. He remained asymptomatic and well 3
months after discontinuation of prednisolone.
Discussion
Tuberculosis and leprosy co infection is more
common in middle age men with the first infection
being leprosy, in particular lepromatous leprosy1.
Systemic steroid treatment for leprosy reactions
was thought to be a predisposing factor to M
tuberculosis infection. However, the TRIPOD
studies that investigated the effect of 16 weeks
prednisolone therapy for nerve impairment did
not report the occurrence of tuberculosis in their
patients5. Rajagopalan et al identified malnutrition
in more than 80% of co infected patients, about 4%
were on steroid or immunosuppressive therapy1.
Only 1 out of 106 patients had diabetes mellitus1.
Our patient had diabetes, was well nourished and
was not on corticosteroid.
Leprosy reaction is common in co infected patients,
we reviewed the literature to identify the clinical
characteristics and risk factors for leprosy reaction
in these patients. The findings are summarized
in Table 1. Most patients were middle aged men.
Leprosy, mainly the lepromatous type was the
Figure 1. Chest radiograph showed consolidation, fibrosis and
cavitations at the right upper zone.

Malaysian Journal of Dermatology
MJD 2016 Dec Vol 3749
Parameter /
Authors
Argawal et al. 20006
Lee et al. 20037
Argawal et al. 20078
Sreerama-reddy et
al. 20079
McIver et al. 201110
Prasad et al. 201011
Trindade et al.
201312
Parise-Fortes et al.
201413
Rawson et al. 20142
Quyum et al. 201514
Sendrasoa et al.
201515
Age,
gender
40, M
63, M
34, F
65, M
50, M
10, M
31, M
31, M
46, F
59, M
18, M
38, M
-
49, M
Disease
diagnosed
first
TB
TB
TB
Leprosy
Leprosy
Leprosy
Leprosy
TB
Leprosy
Both
Leprosy
Leprosy
TB
Leprosy
Duration to
diagnosis of
second disease
weeks
4 months
weeks
NA
2 years after
completed MDT
1 year
7 months
3 months
1 month
NA
9 months
3 years
6 months
13 months
Type of
leprosy
LL
BL
BL
BL
LL
-
BL
BB-BT
BT-BB
LL
LL
LL
LL
LL
Site of
TB
Pulm
Pulm
Pulm
Pulm
Pulm,
peritoneal
Pulm
Pulm
Pleura
Pulm
Perianal
Pulm
CNS
Skin
Pulm
Type of
lepra
reaction
II
I
I
Neuritis
II
II
II
I
I
II
Neuritis
II
II
II
Time lepra reaction
occurred
2 months on
MDT+anti TB
4 months on anti
TB, at diagnosis of
leprosy
20 days on anti
TB, at diagnosis of
leprosy
Before diagnosis
of TB
Recurrent before
diagnosis of TB
Recurrent before
and weeks after anti
TB
At diagnosis of TB,
6 months on MDT
3 months on anti
TB, at diagnosis of
leprosy
At diagnosis of
leprosy and 6
months on anti TB
At presentation, and
? recurrent before
treatment of both
diseases
NA
NA
At diagnosis of
leprosy & before
treatment of both
diseases
1 month after
completed MDT,
before TB diagnosed
Imuno-
suppression
Azathioprine +
Prednisolone
(for renal
transplant)
-
Leflunomide
(for rheumatoid
arthritis)
Prednisolone (for
neuritis)
Prednisolone (for
T2R)
-
-
-
Prednisolone (for
T1R)
Prednisolone (for
presumed drug
reaction)
-
-
-
Prednisolone (for
T2R)
Table 1. Summary of cases with leprosy and tuberculosis co infection with leprosy reaction.
– not available, T2R – type II leprosy reaction, Pulm-pulmonary

Malaysian Journal of Dermatology
MJD 2016 Dec Vol 37 50
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