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Therapeutic Strategies

Leishmaniasis

Timothy Berger Bruce Wintroub

Saturday, January 01, 2011

Overview

As with all infectious diseases, the diagnosis of leishmaniasis should be established by identifying the causative agent in the affected tissue by culture, scrapings, or biopsy. Response to therapy is significantly related to the causative species and geographic area in which the infection was acquired. Leishmaniasis occurs in three forms: cutaneous, mucocutaneous, and visceral. Only the therapy of cutaneous leishmaniasis is discussed here.

Old World Leishmaniasis

The following therapy may not apply to disease acquired in Africa. Because mucocutaneous relapse is quite rare in Old World Leishmaniasis, local therapy to the lesions alone is acceptable. The natural history is one of spontaneous healing without therapy. Treatment of lesions in cosmetically insignificant areas is not required.

First Steps

If available, treatment is with paromomycin sulfate 15% and methylbenzethonium chloride 12% in white soft paraffin applied twice daily for 10 days.

Alternative Steps

  1. Chlorpromazine 2% ointment applied as above may also be effective.
  2. Medical: Oral ketoconazole 400-1200 mg/day or rifampin (with or without isoniazid) 600-1200 mg/day until healed.
  3. Surgical: Cryotherapy of individual lesions (forming an ice ball 2 mm beyond the lesion). Surgical excision of solitary small lesions may be curative.
  4. Intralesional antimony (80-100 mg/ml) on alternate days 3 times per week, or once weekly for a minimum of 3 weeks, and at times for several months will be effective in at least two thirds of lesions.

Subsequent Steps

Use antimonial therapy as discussed below for New World Leishmaniasis in Old World cutaneous disease only when standard therapies fail and/or disease is progressive or disfiguring.

Pitfalls

  1. Oral ketoconazole may cause hepatitis. Monitor liver function tests.
  2. Oral rifampin will cause all body secretions to be colored reddish brown. Hepatitis and thrombocytopenia may occur. Rifampin reduces the efficacy of oral contraceptives.
  3. Delay for at least 1 year after apparent complete healing any corrective plastic surgical procedures. During this period local relapse may occur, destroying any benefit gained by the surgical procedures; surgery can trigger reactivation of the infection.

New World Leishmaniasis (American Leishmaniasis)

Response to therapy is clearly species and subspecies related. Mucocutaneous disease is a potential and disastrous complication of New World Leishmaniasis. Treat cases acquired in areas where mucocutaneous disease may occur with systemic agents. L. braziliensis infection should be treated systemically. The CDC will culture potentially infected tissue and speciate the infecting parasite. In addition, they can advise you on the infectious species present in the region where your patient was infected. This information may be used to guide therapy, and will make antimonials available for your patient, since the CDC must release the medication (see CDC website).

First Steps

  1. Treat patients with extensive cutaneous lesions or cutaneous lesions acquired in an area endemic for L. braziliensis with systemic antimonials (i.e., intramuscular or intravenous sodium stibogluconate 20 mg/kg antimony for 20 days). N-Methylglucamine antimonate 50-60 mg/kg/ day may also be used. (Only sodium stibogluconate is available in the United States, and it must be obtained from the Centers for Disease Control.)
  2. Patients with few lesions not acquired in an area endemic for L. braziliensis may be treated with ketoconazole 400-1200 mg/day until healed.

Alternative Steps

Localized cutaneous lesions acquired in areas not endemic for L. braziliensis may be treated with intralesional or topical modalities used for Old World Leishmaniasis

Subsequent Steps

  1. If the lesions have partially, but not completely responded after a single course of systemic antimonial therapy, a second (third, etc.) course may be given after a 10-day rest period. Pentoxyphylline 400 mg 3 times daily may be added to the antimony treatment for enhanced benefit.
  2. Patients failing to respond to antimonial therapy may be treated with liposomal amphotericin B 3 mg/kg/day for days 1-5 with additional doses at days 14 and 21.

Pitfalls

  1. Antimonials are potentially quite toxic; electrocardiographic changes, renal and liver toxicities, vomiting, and myalgias may occur.
  2. Amphotericin B is nephrotoxic; monitoring renal function and serum electrolytes (especially potassium) is required.
  3. Recurrence of apparently "healed" lesions may occur months later, especially in patients treated with topical or intralesional methods. Regular follow up of all patients diagnosed with cutaneous leishmaniasis is recommended.

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