Definisi dan Etiologi

Leprosy, is a chronic infectious disease caused by the acid-fast, rod-shaped bacillus

Mycobacterium leprae, it is a microorganism that has a predilection (liking) for the skin and
peripheral nerves.1 Infection of Mycobacterium leprae causes a wide array of cellular
immune responses. These immunologic events then elicit the second part of the disease, a
peripheral neuropathy with potentially long-term consequences.2
The disease has been known to man since time immemorial (long time, past). DNA taken
from the shrouded remains of a man discovered dated back to 150 A.D.3 in a tomb next to
the old city of Jerusalem shows him to be the earliest human proven to have suffered from
leprosy. The causative agent of leprosy, Mycobacterium leprae, was discovered by G. H.
Armauer Hansen in Norway in 1873, which is why it is also known as Hansens disease. It
was the first bacterium to be identified as causing disease in humans.4,5 In addition to humans,
leprosy has been observed in ninebanded armadillo and three species of primates.6
Lepra adalah penyakit infeksi kronis yang disebabkan oleh bakteri Mycobacterium leprae
yang bersifat acid-fast, berbentuk batang (bacillus) dan memiliki predileksi pada kulit dan
saraf tepi.1 Infeksi oleh Mycobacterium leprae menyebabkan berbagai macam respon seluler
imun. Peristiwa imunologi tersebut kemudian menimbulkan, neuropati saraf perifer dengan
efek jangka panjang2 Mycobacterium leprae, ditemukan oleh G. H. Armauer Hansen di
Norwegia pada tahun 1873, karena itu, Lepra juga dikenal sebagai penyakit Hansen. Bakteri
ini adalah bakteri pertama yang diidentifikasi menyebabkan penyakit pada manusia.4,5 Selain
pada manusia, Lepra telah ditemukan pada hewan ninebanded armadillo dan tiga spesies
primata.6
Patofisiologi dan Patogenesis
Those living in endemic areas with poor conditions such as inadequate bedding,
contaminated water, and insufficient diet, or other diseases that compromise immune function
are at highest risk for acquiring M. leprae infection.1The exact mechanism of transmission of
leprosy is not known, but the most widely held belief is that the disease is transmitted by
direct contact between people with leprosy and healthy people.7 The entry route of M. leprae
into the human body is also not definitively known. The skin and the upper respiratory tract
are most likely; however, recent research increasingly favours the respiratory route.8,9 After
entering the body, bacilli migrate towards the neural tissue and enter the Schwann cells. To do
so, M. Leprae uses PGL-1, a major unique glycoconjugate on the its surface then M. leprae
binds to the G domain of the alpha-chain of laminin 2 (found only in peripheral nerves) in the
basal lamina, causing demyelination.10 Once entering the Schwann cells, Bacilli start
multiplying slowly (about 12-14 days for one bacterium to divide into two) within the cells,
get liberated from the destroyed cells and enter other unaffected cells. Till this stage person
remains free from signs and symptoms of leprosy.1 Their slow replication within the
Schwann cells eventually stimulates a cell-mediated immune response, which creates a
chronic inflammatory reaction. As a result, swelling occurs in the perineurium, leading to
ischemia, fibrosis, and axonal death.10 This also includes neuropathy begining as local
anesthesia that, if left untreated, can develop into paralysis and crippling deformities.11 In
vivo, M leprae has also been demonstrated to reprogram Schwann cells to de-differentiate
into mesenchymal stem cells, which may explain the spread of bacteria to other non-neural
tissues.12

Leprosy can manifest in different forms, depending on the host response to the organism.2
Leprosy is classified within two poles of the disease with transition between the clinical
forms.13 Clinical, histopathological,
and immunological criteria by the Ridley-Jopling system identify five forms of leprosy:
tuberculoid polar leprosy (TT), borderline tuberculoid (BT),midborderline (BB), borderline
lepromatous (BL), and lepromatous polar leprosy (LL).1 The classification of the disease
typically changes as it evolves during its progression or management. Individuals who have a
vigorous cellular immune response to M leprae have the tuberculoid form of the disease that
usually involves the skin and peripheral nerves. Individuals with minimal cellular immune
response have the lepromatous form of the disease, which is characterized by extensive skin
involvement.2
Bagi yang tinggal di daerah endemik dengan kondisi yang kurang layak seperti tempat tidur
yang tidak memadai, air yang terkontaminasi, dan pola makan yang tidak memadai, atau
penyakit lain yang membahayakan fungsi kekebalan tubuh berada pada risiko tertinggi untuk
memperoleh infeksi M. leprae.1 Pada saat ini, mekanisme penularan lepra yang tepat tidak
diketahui, tapi diduga bahwa penyakit ini ditularkan melalui kontak langsung antara penderita
lepra dengan orang yang tidak terinfeksi.7 rute masuknya M. leprae ke dalam tubuh manusia
juga tidak diketahui dengan pasti. Kemungkinan terbesar adalah melalui kulit dan saluran
pernapasan; Namun, penelitian terbaru lebih mengarah pada saluran pernafasan.8,9 Setelah
memasuki tubuh, M. leprae bermigrasi ke arah jaringan saraf dan masuk ke dalam sel
Schwann. M. Leprae melakukan ini dengan menggunakan PGL-1, sebuah glycoconjugate
unik yang terdapat pada permukaannya. Menggunakan ini, maka M. leprae dapat mengikat
domain G dari rantai alpha- laminin 2 (yang ditemukan pada saraf perifer) di lamina basal
dan menyebabkan demyelinasi.10 Begitu memasuki sel Schwann, Bacilli mulai berkembang
biak secara perlahan (sekitar 12-14 hari untuk bermitosis sekali) dalam sel, lalu setelah sel
hancur, keluar dan memasuki sel-sel lain yang belum terinfeksi. Sampai tahap ini, penderita
tetap bebas dari tanda-tanda dan gejala lepra.1 Replikasi lambat M. Leprae dalam sel
Schwann akhirnya merangsang respon kekebalan dari tubuh yang dimediasi oleh sel, yang
akhirnya menciptakan reaksi inflamasi kronis. Akibatnya, terjadi pembengkakan di
perineurium, yang menyebabkan iskemia, fibrosis, dan kematian akson.10 Neuropati juga
termasuk dalam salah satu akibat dari infeksi saraf oleh M. Leprae. Awalnya neuropati
merupakan anestesi lokal yang jika tidak segera ditangani, dapat berkembang menjadi
kelumpuhan dan deformitas.11
Lepra dapat bermanifestasi dalam bentuk yang berbeda-beda, tergantung pada respon agen
kepada organism.2 Sistem Ridley-Jopling mengklasifikasi Lepra dalam lima bentuk:
tuberculoid polar leprosy (TT), borderline tuberculoid (BT), midborderline (BB), borderline
lepromatous (BL), dan lepromatous polar leprosy (LL).1 Klasifikasi ini biasanya berubah
sesuai perkembangan penyakit. Individu yang memiliki respon imun seluler yang kuat
terhadap M. leprae memiliki bentuk penyakit tuberkuloid yang biasanya melibatkan kulit dan
saraf perifer. Individu dengan respon imun selular lemah memiliki bentuk penyakit
lepromatous, yang ditandai dengan keterlibatan kulit yang luas2

WHO classifies leprosy into two categories according to the number of lesions and the
presence of bacilli on a skin smear. This method is useful in countries such as Indonesia
where biopsy analysis is often unavailable.2
o
Paucibacillary leprosy is characterized by 5 or fewer lesions with absence of
organisms on smear. Paucibacillary leprosy generally includes the tuberculoid and
borderline lepromatous categories from the Ridley-Jopling system.
o
Multibacillary leprosy is marked by 6 or more lesions with possible
visualization of bacilli on smear. Lepromatous leprosy, borderline lepromatous leprosy, and
midborderline leprosy on the Ridley-Jopling scale are included in the multibacillary
leprosy category.
WHO mengklasifikasikan kusta menjadi dua kategori sesuai dengan jumlah lesi dan adanya
bakteri pada smear kulit. Metode ini berguna di negara seperti Indonesia di mana analisis
biopsi sering tidak tersedia.2
Lepra paucibacillary, yang ditandai dengan 5 lesi dan tidak adanya organisme di
smear. Pada umumnya lepra paucibacillary meliputi tuberculoid polar leprosy (TT) dan
borderline tuberculoid (BT), dari sistem Ridley-Jopling.
Lepra multibacillary ditandai dengan 6 lesi dengan kemungkinan terdapat bacillus
pada smear. Midborderline (BB), borderline lepromatous (BL), dan lepromatous polar
leprosy (LL) pada skala Ridley-Jopling termasuk dalam kategori ini.

GAMBARAN KLINIS
The bacteria that cause Hansen's disease grow very slowly. It may take 2-10 years before
signs and symptoms appear.14The mean incubation period is 4 years for tuberculoid leprosy
and is 10 years for lepromatous leprosy.10Symptoms mainly affect the skin, nerves, and
mucous membranes (the soft, moist areas just inside the body's openings).14 The organism
grows best at 27-30C; therefore, skin lesions tend to develop in the cooler areas of the body,
with sparing of the groin, axilla, and scalp.2 A disseminated skin condition is often the reason
patients seek care, although they may also complain of numbness and other types of
paresthesia or systemic signs such as fever and weight loss.1
Diagnosis is clinical and is made when the patient has at least 1 of the following cardinal
signs specified by the World Health Organization: hypopigmented or erythematous macules
with sensory loss; thickened peripheral nerves; or positive acid-fast skin smear or skin biopsy
with loss of adnexa at affected sites. 15 Leprosy is treated with a multidrug combination of
rifampicin, clofazimine, and dapsone. However, even with proper multidrug therapy (MDT),

the consequent sensory and motor damage results in the deformities and disabilities
associated with leprosy.1
Bakteri yang menyebabkan penyakit Hansen tumbuh dengan sangat lambat. Diperlukan
sekitar 2-10 tahun sebelum tanda-tanda dan gejala muncul.14 Rata-rata masa inkubasi adalah 4
tahun untuk lepra tuberkuloid dan 10 tahun untuk lepra lepromatous.10 Gejala lepra
mempengaruhi kulit, saraf, dan membran mukosa.14 M. leprae tumbuh optimal pada suhu 2730 C; oleh karena itu, lesi kulit cenderung berkembang di daerah-daerah yang lebih dingin
pada tubuh.2 Kondisi kulit pasien akibat M. Leprae sering menjadi alasan pertama pasien
mencari pertolongan, mereka juga mungkin mengeluh mati rasa, demam dan berat badan
yang berkurang.1
Pasien di diagnosis dengan lepra jika memiliki setidaknya salah satu dari tanda-tanda berikut
yang ditetapkan oleh World Health Organization: hipopigmentasi atau makula eritematosa
dengan hilangnya kepekaan saraf sensori; saraf perifer menebal; atau smear kulit positif acidfast atau biopsi kulit dengan hilangnya adneksa di lokasi yang terkena dampak. 15 Lepra dapat
diobati dengan kombinasi multidrug rifampicin, clofazimine, and dapsone. Namun, bahkan
dengan terapi multidrug (MDT), kerusakan saraf sensorik dan motorik bisa mengakibatkan
cacat terkait dengan leprosy.1
1. RameshMarne Bhat, Chaitra Prakash. Leprosy: An Overview of Pathophysiology.
Interdisciplinary Perspectives on Infectious Diseases. 2012
2. Darvin Scott Smith, MD, MSc, DTM&H. Medscape. Jul 22, 2014. Available from:
http://emedicine.medscape.com/article/220455-overview#showall
3. DNA of Jesus-Era ShroudedMan in Jerusalem Reveals Earliest Case of Leprosy,
2009.
4. G. H. A. Hansen, Investigations concerning the etiology of leprosy, Norsk Magazin
for Lgevidenskaben, vol. 4, pp. 188, 1874 (Norwegian).
5. L. M. Irgens, The discovery of the leprosy bacillus, Tidsskrift for den Norske
Laegeforening, vol. 122, no. 7, pp. 708709, 2002.
6. O. Rojas-Espinosa and M. Lvik, Mycobacterium leprae and Mycobacterium
lepraemurium infections in domestic and wild animals, OIE Revue Scientifique et
Technique, vol. 20, no. 1, pp. 219251, 2001.
7. British Medical Journal Best Practice. Available from: URL
http://bestpractice.bmj.com/bestpractice/monograph/923/basics/pathophysiology.html
8. R. J. W. Rees and A. C. McDougall, Airborne infection with Mycobacterium leprae
in mice, Journal of Medical Microbiology, vol. 10, no. 1, pp. 6368, 1977.
9. S. Chehl, C. K. Job, and R. C. Hastings, Transmission of leprosy in nude mice,
American Journal of Tropical Medicine and Hygiene, vol. 34, no. 6, pp. 11611166,
1985.
10. Felisa S Lewis, MD. Medscape. Apr 09, 2014.
http://emedicine.medscape.com/article/1104977-overview#showall
11. Malcolm S. Duthie, Thomas P. Gillis, Steven G. Reed. Advances and hurdles on the
way toward a leprosy vaccine. Human Vaccines. November 2011.
12. Masaki T, Qu J, Cholewa-Waclaw J, Burr K, Raaum R, Rambukkana A.
Reprogramming adult Schwann cells to stem cell-like cells by leprosy bacilli
promotes dissemination of infection. Cell. 2013 Jan 17. 152(1-2):51-67. [Medline].
13. Ferreira J, Mengue SS, Wagner MB, Duncan BB. Estimating hidden prevalence in
Hansens disease through diagnosis delay and grade of disability at time of diagnosis.
Int J Lepr Other Mycobact Dis 2000; 68:464-73; PMID:11332290.

14. Centers for Disease Control and Prevention. April 29, 2013.
http://www.cdc.gov/leprosy/symptoms/index.html
15. K. Eichelmann,_ S.E. Gonzlez Gonzlez, J.C. Salas-Alanis, J. Ocampo-Candiani.
Leprosy. An update: definition, pathogenesis, classification, diagnosis, and treatment.
Actas Dermosifiliogr. 2013
16.