Treatment of leprosy

Several drugs are used in combination in multidrug therapy (MDT). (See table) These drugs must never be used alone as monotherapy for leprosy. Dapsone, which is bacteriostatic or weakly bactericidal against M. leprae, was the mainstay treatment for leprosy for many years until widespread resistant strains appeared. Combination therapy has become essential to slow or prevent the development of resistance. Rifampicin is now combined with dapsone to treat paucibacillary leprosy. Rifampicin and clofazimine are now combined with dapsone to treat multibacillary leprosy. A single dose of combination therapy has been used to cure single lesion paucibacillary leprosy: rifampicin (600 mg), ofloxacin (400 mg), and minocycline (100 mg). The child with a single lesion takes half the adult dose of the 3 medications. WHO has designed blister pack medication kits for both paucibacillary leprosy and for multibacillary leprosy. Each easy-to use kit contains medication for 28 days. The blister pack medication kit for single lesion paucibacillary leprosy contains the necessary medication for the one time administration of the 3 medications. Any patient with a positive skin smear must be treated with the MDT regimen for multibacillary leprosy. The regimen for paucibacillary leprosy should never be given to a patient with multibacillary leprosy. Therefore, if the diagnosis in a particular patient is uncertain, treat that patient with the MDT regimen for multibacillary leprosy. Ideally, the patient should go to the leprosy clinic once a month so that clinic personnel may supervise administration of the drugs prescribed once a month. However, many countries with leprosy have poor coverage of health services and monthly supervision of drug administration by health care workers may not be possible. In these cases, it may be necessary to designate a responsible third party, such as a family member or a person in the community, to supervise the monthly drug administration. Where health care service coverage is poor and supervision of the monthly administration of drugs by health workers is not possible, the patient may be given more than the 28 days supply of multidrug therapy blister packs. This tactic helps make multidrug therapy easily available, even to those patients who live under difficult conditions or in remote areas. Patients who ask for diagnosis and treatment are often sufficiently motivated to take full responsibility for their own treatment of leprosy. In this situation, it is important to educate the patient regarding the importance of compliance with the regimen and to give the patient responsibility for taking his or her medication correctly and for reporting any untoward signs and symptoms promptly. The patient should be warned about possible lepra reactions. WHO Recommended treatment regimens 6 month regimen for Paucibacillary (PB) Leprosy Dapsone Adult 50 - 70 kg Rifampicin

100 mg 600 mg Given daily Given once a month under supervision

Child 50 mg 450 mg 10 - 14 yearsa Given daily Given once a month under supervision
a

Adjust dose appropriately for child less than 10 years. For example, dapsone 25 mg daily

and rifampicin 300 mg given once a month under supervision 12 month regimen for Multibacillary (MB) Leprosy Dapsone Adult 50 - 70 kg Child 10 - 14 yearsb
b

Rifampicin 600 mg Given once a month under supervision 450 mg Given once a month under supervision 50 mg Given daily 50 mg Given every other day

Clofazimine AND 300 mg Given once a month under supervision AND 150 mg Given once a month under supervision

100 mg Given daily 50 mg Given daily

Adjust dose appropriately for child less than 10 years. For example, dapsone 25 mg daily,

rifampicin 300 mg given once a month under supervision, clofazimine, 50 mg given twice a week, and clofazimine 100 mg given once a month under supervision Single Lesion Paucibacillary (SLPB) Leprosy (one time dose of 3 medications taken together) Rifampicin Ofloxacin Minocycline Adult 50 - 70 kg 600 mg 400 mg 200 mg 100 mg 50 mg

Child 300 mg c 5 - 14 years

c

Not recommended for pregnant women or children less than 5 years

Treatment of lepra reactions

During the course of leprosy, immunologically mediated episodes of acute or subacute inflammation known as reactions may occur in up to 25% of patients with paucibacillary leprosy and as much as 40% in multibacillary leprosy. Clinical indications of a reaction are nerve pain, loss of sensation and loss of function. The reactions may rapidly cause severe and irreversible nerve damage and must always be treated promptly. If a patient does not respond to lepra reaction treatment within 4 weeks or his/her condition deteriorates at any time during lepra reaction treatment, send that patient immediately to the nearest specialist centre. During a lepra reaction, do not interrupt leprosy multidrug therapy. Treatment with multidrug therapy reduces the frequency and severity of lepra reactions. Type 1 lepra reactions or reversal reactions are associated with the development of M. leprae antigenic determinants. They are delayed hypersensitivity reactions and may occur in both

paucibacillary leprosy and multibacillary leprosy. In type 1 lepra reactions, there is a high risk of permanent damage to the peripheral nerve trunks. If the reaction is mild and there is no evidence of neuritis (pain, loss of sensation or function), the reaction should be treated with analgesics, such as acetylsalicylic acid or paracetamol. However, if there is nerve involvement, treat type 1 reactions with analgesics and corticosteroids, such as oral prednisolone. The usual course begins with 40 - 60 mg daily (up to a maximum of 1 mg/kg), and the reaction is generally controlled within a few days. The dose is then gradually reduced weekly or fortnightly and eventually stopped. Most reversal reactions and neuritis can be treated successfully under field conditions with a standard 12-week course of prednisolone but some authorities claim that corticosteroids need to be continued for much longer periods of time. Type 2 lepra reactions (erythema nodosum leprosum), are associated with circulation and tissue deposition of immune complexes. They are an antibody response or immune complex response to M. leprae antigenic determinants which occur only in multibacillary leprosy. Therapy for type 2 reactions may include analgesics, such as acetylsalicylic acid or paracetamol, and corticosteroids, such as oral prednisolone. In patients with severe type 2 reactions, who do not respond to corticosteroids or in whom corticosteroids are contraindicated, clofazimine at high doses or thalidomide may be used under close medical supervision. Clofazimine often requires 4-6 weeks before an effect is seen, and therefore must never be used as the sole drug for treatment of severe type 2 reactions. However, it may be useful for reducing or withdrawing corticosteroids from patients who have become dependent on corticosteroids. The clofazimine dose for treatment of severe type 2 reactions is 300 mg daily, which should be given in 3 doses of 100 mg each. The total duration of this high dose of clofazimine should not exceed 12 months. Thalidomide should be avoided in women of childbearing age since it is a proven teratogen. If this is not possible, it is imperative that pregnancy is excluded before this treatment is initiated. Effective contraception must be used during the 4 weeks preceding and following treatment as well as during the treatment period. Should pregnancy occur despite these precautions, there is a high risk of severe malformation of the fetus.
http://apps.who.int/medicinedocs/en/d/Jh2988e/6.html

Table 1. Classification of leprosy

CLASSIFICATION OF LEPROSY Clinical findings Type of lesions LL Macules, papules, nodules, diffuse infiltration Numerous BL Macules, papules, plaques, infiltration Many BB Plaques and domeshaped, punched-out lesions Many BT Infiltrated plaques TT Infiltrated plaques, often hypopigmented I Macules, often hypopigmented

Number

Single, usually One or few (up with satellite to 5) lesions lesions, or more than 5 lesions Asymmetric Localized, asymmetric Well-defined, sharp borders

One or few

Distribution Symmetric Definition

Tendency to symmetry

Evident asymmetry

Variable Not always defined

Vague, Less welldifficult to defined distinguish borders normal versus affected skin Not affected Diminished Many

Less wellWell-defined, defined borders sharp borders

Sensation

Diminished Many

Absent Few (1+), if any, detected

Absent None detected

Impaired Usually none detected

Bacilli in Many (globi) skin lesions

Adapted from Ramos-e-Silva M , Castro MCR. Mycobacterial infections. In: Bolognia JL; Jorizzo JL; Rapini RP. Dermatology. 2nd edition. London: Mosby, 2008; 1109.

Legend LL: lepromatous leprosy BL: borderline LL BB: mid-borderline leprosy BT: borderline TT TT: tuberculoid leprosy I: indeterminate.

http://dermatology.cdlib.org/1512/articles/leprosy/table1.htm

KLASIFIKASI LEPRA Gambaran LL klinis Tipe lesi Makula, papul, nodul, infiltrasi difus Banyak BL BB BT TT Plak infiltrasi, sering hipopigmentasi I Makula, sering hipopigmentasi

Makula, Plak dan lesi Plak papul, plak, berbentuk kubah infiltrasi infiltrasi (domeshaped, punched-out) Banyak Banyak Tunggal, biasanya dengan lesi satelit, atau lebih dari 5 lesi Asimetris

Jumlah

Satu atau sedikit Satu atau sedikit (sampai dengan 5)

Distribusi

Simetris

Cenderung untuk simetris Kurang tegas

Jelas asimetris

Terlokalisir, asimetris Tegas

Variabel

Batas

Samar-samar, sulit untuk membedakan antara kulit normal dengan lesi Tidak terkena

Kurang tegas

Tegas

Tidak selalu

Sensasi

Berkurang

Berkurang Banyak

Absen Sedikit

Absen Tidak ada

Terganggu Biasanya tidak ada

Basil pada Banyak (globus) Banyak lesi kulit

Legend LL: lepromatous leprosy BL: borderline LL BB: mid-borderline leprosy BT: borderline TT TT: tuberculoid leprosy I: indeterminate.

Penatalaksanaan untuk reaksi kusta : A. Dalam reaksi kusta tipe 1, ada risiko tinggi kerusakan permanen pada batang saraf perifer. Jika reaksi ringan dan tidak ada bukti neuritis (nyeri, hilangnya sensasi atau fungsi), reaksi harus diobati dengan analgesik, seperti asam asetilsalisilat atau parasetamol. Namun, jika ada keterlibatan saraf, pengobatan reaksi tipe 1 dengan analgesik dan kortikosteroid, seperti prednisolon oral. Pengobatan yang biasa dimulai dengan 40 - 60 mg sehari (maksimum 1 mg / kg), dan reaksi umumnya dikendalikan dalam beberapa hari. Dosis tersebut kemudian dikurangi secara bertahap mingguan atau setiap dua minggu dan akhirnya berhenti. Kebanyakan reaksi reversal dan neuritis bisa diobati dengan sukses dengan terapi prednisolon standar selama 12 minggu.

B. Reaksi tipe 2 kusta (eritema nodosum leprosum), berhubungan dengan deposisi kompleks imun jaringan dan sirkulasi. ENL adalah respon antibodi atau respon komplek imun terhadap M. leprae determinan antigenik yang hanya terjadi pada kusta multibacillary. Terapi untuk reaksi tipe 2 termasuk analgesik, seperti asam asetilsalisilat atau parasetamol, dan kortikosteroid, seperti prednisolon oral. Pada pasien dengan reaksi tipe 2 berat yang tidak berespon terhadap kortikosteroid atau yang kontraindikasi pada kortikosteroid, clofazimine pada dosis tinggi atau thalidomide dapat digunakan di bawah pengawasan medis. Clofazimine sering membutuhkan 4-6 minggu sebelum efek terlihat, dan karena itu tidak harus digunakan sebagai obat tunggal untuk pengobatan reaksi tipe 2 yang parah. Namun, mungkin akan berguna untuk mengurangi atau penarikan kortikosteroid dari pasien yang telah menjadi tergantung pada kortikosteroid. Dosis clofazimine untuk pengobatan reaksi tipe 2 adalah berat 300 mg sehari, yang diberikan dalam 3 dosis 100 mg. Total durasi dari dosis tinggi clofazimine tidak boleh melebihi 12 bulan. Thalidomide harus dihindari pada wanita usia subur karena terbukti merupakan teratogen.

Table 1 WHO grading of disability and deformity index hands and feet and eyes Tangan dan kaki Grade 0 Grade 1 Grade 2 Mata Grade 0 Tidak ada kelainan pada mata karena kusta, tidak ada gangguan penglihatan Grade 1 Terdapat kerusakan pada mata karena lepra, tetapi gangguan penglihatan tidak parah (visus 6/60 or lebih baik, masih dapat menghitung jari dari jarak 6 meter). Grade 2 Gangguan penglihatan yang parah (visus lebih jelek dari 6/60, tidak dapat menghitung jari dari jarak 6 meter) lagoftalmos, iridosiklitis and opasitas pada kornea. Tidak ada anestesi, tidak ada kelainan atau kerusakan yang terlihat. Anestesi, tetapiu tidak ada kelainan atau kerusakan yang terlihat. Terdapat kelainan atau kerusakan yang terlihat.