Leishmaniasis: Visceral or Kala-Azar, Cutaneous, and Mucocutaneous Leishmaniasis (Espundia)
Primary Distribution: East and North Africa, Middle East, Southern Europe, Central, South, and East Asia, South America, West Mexico.
Agent and Vector: The protozoal parasite species Leishmania is transmitted through the bite of female sandflies (phlebotomine) as follows:
Incubation: Usually 2-6 months or longer. Relapse may occur as many as 10 years after first episode. Local trauma sometimes activates latent infection in cutaneous leishmaniasis.
Clinical Findings and Treatment: Visceral Leishmaniasis or Kala-Azar
Signs and Symptoms: Cardinal signs of visceral leishmaniasis (VL) are prolonged fever, splenomegaly, anemia, leukopenia, or hypergammaglobulinemia. A cutaneous nodule may or may not appear at the site of the bite within several days of inoculation. If present, the nodule remains, but in most cases, no other symptoms are present for at least several months. Systemic symptoms include gradual onset fever that often rises and falls twice/day, fatigue, weight loss, dizziness, cough, and diarrhea. Visceral manifestations include pronounced splenomegaly (hard, non-tender) and to a lesser extent hepatomegaly. Other manifestations may include generalized lymphadenopathy; hyperpigmented skin of the forehead, abdomen, hands, and feet in light-skinned persons; skin lesions in dark-skinned persons; signs of bleeding (petechiae, epistaxis, bleeding gums); jaundice and ascites; and progressive wasting. Onset may also be acute, with the above manifestations appearing a few weeks after infection.
Complications: Progressive wasting or intercurrent infections (e.g., pneumonia, tuberculosis, diarrhea) may lead to death. Post kala-azar cutaneous leishmaniasis may occur as many as 10 years after the first episode. Lesions may resemble Hansen's disease and include hypopigmented macules, nodules, and erythematous patches. Leshmaniasis may occur as an opportunistic infection in immunocompromised persons. The disease may also be passed from an asymptomatic mother to her child. Laboratory Findings: Leukopenia, hypergammaglobulinemia, hypoalbuminemia; thromboctopenia with hemorrhagic fever.
Diagnosis: Presence of cardinal signs noted above, in addition to living in or visiting endemic area lead to suspicion of leishmaniasis. The organism is present in bone marrow or splenic aspirate (most sensitive), blood, and nasopharyngeal secretions. If parasites are present in sufficient concentration, light microscopy of giemsa-stained slides reveals amastigotes, the tissue form of the parasite. Direct agglutination and ELISA are positive early and the leishmanin skin test is positive only after active disease.
Differential Diagnosis: Brucellosis, leprosy, schistosomiasis, trypanosomiasis (African), leukemia, lymphoma, malaria, typhoid, liver diseases, other entities.
Treatment: Treatment has traditionally been unsatisfactory because of drug toxicities, poor responses, multiple disease syndromes, and other factors - including recently, the emergence of antimony-resistant strains. Orally administered miltefosine 100 mg/day (2.5 mg/kg/day) for four weeks has recently shown great promise (cure rate of 95% at six months post-treatment) in the treatment of Indian visceral leishmaniasis (see Jha et al in references). Other treatments include sodium stibogluconate (a pentavalent antimony compound) 20 mg/kg/day IM or IV once daily for 40 days if the disease was contracted in India and 28 days if contracted elsewhere. Sodium Stb is not FDA approved and must be obtained from the CDC. Side effects of sodium stibogluconate include changes in liver function, biochemical pancreatitis, EKG changes, musculoskeletal symptoms, thromboctopenia, and others. Second line treatments (used in some cases as a first line treatment) are amphotericin B total IV dose of 6-20 mg/kg over 20 doses (better results with higher dosing) or L-ampho 3.0 mg/kg IV day 1, day 5, day 10. Second line treatments include IM pentamidine 2-4 mg/kg/day for 15 days (or every other day) or IM aminosidine 15 mg/kg/day for 30 days. Second line medications (except for miltefosine) are sometimes given in combination with antimony compounds.
Clinical Findings and Treatment: Cutaneous Leishmaniasis
Signs and Symptoms: Cutaneous leishmaniasis (CL) is characterized by single or multiple lesions typically progress from papules to nodules to non-ulcerated dry plaques or ulcers (with raised indurated border and central depression) that usually are painless unless secondarily infected. The appearance of lesions depends largely on the host's immune response. Lesions are sometimes described as wet or dry. Distribution may be a single primary lesion, multiple primary lesions, and/or satellite lesions. Low-grade fever, regional lymphadenopathy and/or lymphangitis, and lesion pruritis or pain may be present. Most new world cutaneous lesions are ulcers as are some old world cutaneous lesions. In many cases, healing is spontaneous within months or years of onset. In other cases, however, the disease is progressive with visceral manifestations or spreading skin lesions. Photo: Cutaneous leishmaniasis. Courtesy of Stephen Williamson and his Dad.
Complications: Mucosal leishmaniasis may occur as a sequela of new world cutaneous leishmaniasis (see below). Diffuse cutaneous leishmaniasis (DCL) is characterized by non-ulcerating nodules over the entire body, resembling lepromatous leprosy and is usually associated with L. mexicana or L. aethiopica infection. Diffuse cutaneous leishmaniasis (DCL) tends to be refractory to treatment. Leishmaniasis recidivans is recurrent leishmaniasis that is resistant to treatment. Cutaneous leshmaniasis may occur as an opportunistic infection in immunocompromised persons. Laboratory Findings: There are no specific laboratory findings characteristic of primary CL.
Diagnosis: Presence of cardinal signs noted above and geographic risk lead to suspicion of leishmaniasis. The organism is present in histopathologic studies of slit skin smears or in cultures - though neither is highly reliable. Leishmanin skin test is positive only after active disease.
Differential Diagnosis: Numerous primary and secondary skin diseases/conditions such as other tropical ulcers, impetigo, infected insect bites, leprosy, lupus vulgaris, tertiary syphilis, yaws, blastomycosis, skin cancer, and others.
Treatment: CL generally heals spontaneously in 5-12 months in non-immunocompromised patients. Treatment depends on whether the patient is immunocompromised and/or at risk for mucosal leishmaniasis (in which case, treatment is provided) and on site and severity of lesions, with metastatic lesions treated and unobtrusive lesions not always treated. First-line treatment is IM or IV sodium Stb 20 mg/kg/day for 20 days. Second-line treatment of Old World CL is topical aminosidine with methylbenzonium chloride bid for 10 days. Second-line treatment of New World CL is oral ketoconazole 600 mg/day for 28 days or IM pentamidine 3 mg/kg/day every other day for a total of four doses. See comments above on the promising use of oral miltefosine.
Clinical Findings and Treatment: Mucocutaneous Leishmaniasis (Espundia)
Signs and Symptoms: Mucocutaneous leishmaniasis (MCL) is a sequela of new world cutaneous leishmaniasis and results from direct extension or hematogenous or lymphatic metastasis to the nasal or oral mucosa. In most cases, naso-oropharyngeal symptoms appear several years after resolution of the primary lesion(s), but may also appear while the primary lesions are still present or decades later. Manifestations of mucocutaneous leishmaniasis include chronic nasal symptoms, especially of the anterior nasal septum (leading to development of the characteristic "tapir nose") and progressing to extensive naso-oropharyngeal destruction. Secondary bacterial (or fungal) infections and associated problems are common.
Complications: Mucosal leishmaniasis is, itself, a complication. Secondary infections and associated problems are common. Laboratory Findings: There are no specific laboratory findings characteristic of MCL.
Diagnosis: Presence of cardinal signs, positive history, and geographic risk lead to suspicion of mucocutaneous leishmaniasis. Diagnosis is difficult because amastigotes are scarce in the usual sources (scrapings, tissue aspirates, biopsy). Culture and serologic tests are usually necessary.
Differential Diagnosis: paracoccidioidomycosis, polymorphic reticulosis, Wegener's granulomatosis, lymphoma, histoplasmosis, yaws, gummatous syphilis, tuberculosis, nasopharyngeal carcinoma, other destructive lesions.
Treatment: Treatment is difficult and cure rates decrease with advanced disease. Treatment is as for cutaneous leishmaniasis.
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