Leishmaniasis natural history
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Alejandro Lemor, M.D. [2]
Overview
The term leishmaniasis encompasses multiple clinical syndromes (cutaneous, mucosal, and visceral forms), which result from infection of macrophages in the dermis, in the naso-oropharyngeal mucosa, and throughout the reticuloendothelial system, respectively. For all three forms, the infection can range from asymptomatic to severe. Cutaneous and mucosal leishmaniasis can cause substantial morbidity, whereas visceral leishmaniasis can be life threatening.
Natural History
Cutaneous Leishmaniasis [1]
- This is the most common form of leishmaniasis, both in general and in U.S. travelers.
- Unless otherwise specified, cutaneous leishmaniasis refers to localized cutaneous leishmaniasis, rather than to much less common forms, such as diffuse cutaneous leishmaniasis and disseminated cutaneous leishmaniasis.
- In general, cutaneous leishmaniasis causes skin lesions, which can persist for months, sometimes years.
- The skin lesions usually develop within several weeks or months after the exposure but occasionally first appear years later (for example, in the context of trauma or immunosuppression).
- The lesions typically evolve from papules to nodular plaques to ulcerative lesions, with a raised border and central depression, which can be covered by scab or crust; some lesions persist as nodules.
- The lesions usually are painless but can be painful, especially if ulcerative lesions become infected with bacteria or if the lesions are near a joint.
- The healing process typically results in atrophic scarring.
- Even patients with localized cutaneous leishmaniasis quite commonly develop more than one primary lesion (on the same or different parts of the body), satellite lesions, regional lymphadenopathy (occasionally bubonic), and/or nodular lymphangitis (sporotrichoid-like subcutaneous nodules).
- Sometimes lymphadenopathy is noticed first, before skin lesions develop.
Mucosal Leishmaniasis [1]
- Mucosal leishmaniasis (also called espundia) traditionally refers to a metastatic sequela of New World cutaneous infection, which results from dissemination of parasites from the skin to the naso-oropharyngeal mucosa.
- Adequate systemic treatment of cutaneous leishmaniasis caused by these species is thought to reduce the risk for mucosal disease, but some risk may remain.
- The magnitudes and determinants (parasite and host factors) of the risks for mucosal dissemination and for mucosal disease per se are poorly understood; even for the same species (for example, L. [V.] braziliensis), the risks appear to vary among geographic regions in the Americas.
- Mucosal leishmaniasis usually becomes clinically evident within several years (sometimes as long as decades) of the original cutaneous lesions, which typically were not treated at all or were treated suboptimally. However, mucosal and skin lesions may be noted concomitantly (mucocutaneous leishmaniasis), and some patients had subclinical cutaneous infection.
- The initial manifestations of mucosal leishmaniasis usually are persistent, unusual nasal symptoms (such as stuffiness or bleeding), although oral or pharyngeal symptoms sometimes are noticed first.
- If untreated, the disease can progress to ulcerative destruction of the naso-oropharyngeal mucosa (such as perforation of the nasal septum).
Visceral Leishmaniasis [1]
- The general term visceral leishmaniasis encompasses a broad spectrum of severity and manifestations.
- The onset can be chronic, subacute, or acute.
- Although the incubation period generally ranges from weeks to months, asymptomatic infection can become clinically manifest years to decades after the exposure in people who become immunocompromised for other medical reasons (such as HIV/AIDS).
- The stereotypical manifestations of clinically manifest visceral infection include: fever, weight loss (cachexia; wasting), hepatosplenomegaly (usually, the spleen is more prominent than the liver), pancytopenia (anemia, leukopenia, and thrombocytopenia), a high total protein level and a low albumin level, with hypergammaglobulinemia
- Lymphadenopathy may be noted, particularly in some geographic regions, such as Sudan.
- HIV-coinfected patients may have atypical manifestations, such as involvement of the gastrointestinal tract and other organ systems.
Kala-azar
- The term kala-azar—which means black (kala) fever (azar) in Hindi—often is reserved for severe (advanced) cases of visceral leishmaniasis, although the terms kala-azar and visceral leishmaniasis sometimes are used interchangeably.
- If untreated, severe cases of visceral leishmaniasis typically are fatal, either directly from the disease or indirectly from complications, such as secondary (myco)bacterial infection or hemorrhage.
- Some patients develop post kala-azar dermal leishmaniasis (PKDL), a syndrome characterized by skin lesions (such as erythematous or hypopigmented macules, papules, nodules, and patches), typically first noticed and most prominent on the face, that develop at variable intervals after (or during) therapy for visceral leishmaniasis.
- PKDL is best described in cases of L. donovani infection in South Asia and East Africa.
- In general, PKDL is more common, develops earlier, and is less chronic in patients in East Africa.
- For example, in Sudan, PKDL is noted in up to 60% of patients, typically from 0 to 6 months after therapy for visceral leishmaniasis, and often heals spontaneously. *In contrast, in South Asia, PKDL is noted in ~5-15% of patients, on average several years after initial therapy, and usually requires additional treatment. Persons with chronic PKDL can serve as important reservoir hosts of infection.
Complications
- Deadly infections due to immune system damage
- Disfigurement of the face
- Bleeding (hemorrhage)
Prognosis
- The skin lesions of cutaneous leishmaniasis usually heal on their own, even without treatment. [2]
- But this can take months or even years, and the lesions can leave scars. Another potential concern applies to some (not all) types of the parasite found in parts of Latin America: certain types might spread from the skin and cause sores in the mucous membranes of the nose (most common location), mouth, or throat (mucosal leishmaniasis).
- Mucosal leishmaniasis might not be noticed until years after the original sores healed.
- The best way to prevent mucosal leishmaniasis is to ensure adequate treatment of the cutaneous infection.
- If not treated, severe (advanced) cases of visceral leishmaniasis typically are fatal.