Dermatologic Manifestations of Leishmaniasis 

Leishmaniasis is a disease caused by an intracellular protozoa parasite, and it affects as many as 12 million people worldwide, with 1.5-2 million new cases each year. The global incidence of leishmaniasis has increased in recent years because of increased international leisure- and military-related travel, human alteration of vector habitats, and concomitant factors that increase susceptibility, such as HIV infection and malnutrition.

The recent conflicts in Iraq and Afghanistan have led to approximately 2000 laboratory-confirmed cases (and at least double the number of unconfirmed cases) of cutaneous leishmaniasis and 5 laboratory-confirmed cases of visceral leishmaniasis in American soldiers alone from 2003-2008.^{[1, 2]} In Colombia, the military fighting the Fuerzas Armadas Revolucionarias de Colombia (FARC) has seen more than 30,000 cases of leishmaniasis in the last 3 years. Of course, a significantly larger burden of diseases is borne by the local populations of these countries where Leishmania species are endemic. In these populations, leishmaniasis contributes greatly to morbidity and mortality.

Infection is transmitted by the bite of a sandfly, which is usually one half to one third the size of a mosquito. The clinical spectrum of leishmaniasis ranges from a self-resolving cutaneous ulcer to a mutilating mucocutaneous disease and, depending on the species of Leishmania involved, even a lethal systemic illness. See the images below.

Infection with different Leishmania species can lead to a remarkably broad range of disease states. The clinical spectrum can range from insignificant pustules to fatal systemic disease. General understanding of this clinical spectrum, although once believed to be quite predictable, continues to evolve as new diagnostic techniques contribute to the elucidation of the variety of clinical manifestations of an infection with even a single species of Leishmania. The particular species associated with certain disease states originally was determined based only on clinical manifestations and location found. In current practice, molecular techniques have shown a very different parasite-to-disease association than was ever appreciated previously.

Diagnosis is often difficult because of the small size of the protozoa sequestered within macrophages of the skin, bone marrow, and reticuloendothelial system. Therapy has long been a challenge in the more severe forms of the disease and is made more difficult by the emergence of drug resistance. No effective vaccine for leishmaniasis is available.

Also see Leishmaniasis (pediatric focus), Leishmaniasis (infectious disease focus), and Leishmaniasis (emergency medicine focus).

Mammalian reservoirs for the Leishmania parasite include rodents, canines, equines, monkeys, sloth, and humans. In mammalian hosts, the organism exists as a nonflagellated amastigote composed of a large nucleus and a kinetoplast, with an absent or greatly reduced flagellum, that resides in the phagolysosome of the macrophage. The vector is the sandfly, of the genus Phlebotomus in the Old World and of the genus Lutzomyia in the New World, and they ingest amastigotes when drawing a blood meal from an infected host. In the gut of the sandfly, the parasite transforms into flagellated promastigotes and multiplies.

Promastigotes in the gut of the sandfly migrate to the proboscis and are inoculated into a naive host during the insect's next blood meal. The promastigotes enter into or are ingested by the new host's macrophages, where they transform back into amastigotes, multiply, and eventually spread throughout the reticuloendothelial system. Clinical disease becomes apparent within weeks to months after infection, depending on the species of parasite and the host’s immune status.

Similar to the clinical diversity seen in Hansen disease (leprosy), leishmaniasis reflects a complex and still poorly understood interplay between the virulence of the infecting species and the host's immune response. At one extreme, localized cutaneous disease demonstrates a vigorous immune response, with most cases resolving without intervention. This form of the disease exhibits a helper T-cell subtype 1 immune response, with interleukin 2, interferon-gamma, and interleukin 12 as the prominent cytokines that induce disease resolution. At the other extreme, with visceral or diffuse cutaneous disease, patients exhibit relative anergy to the Leishmania organism and have a prominent helper T-cell subtype 2 cytokine profile. The immunomodulation of leishmaniasis has become an area of intense study in the search for new treatments for this disease.

See the images below.

Frequency

United States

Most cases of leishmaniasis in the United States are imported from elsewhere. Predominately, the disease has traditionally been seen in graduate students and Peace Corps workers living in endemic areas for extended periods and returning to the United States after their studies or work abroad. Recently, however, the largest burden has been from returning veterans of Operation Iraqi Freedom.

See the images below.

Although sandflies are found in the United States as far north as upstate New York, and visceral leishmaniasis has been identified in foxhounds in a wide geographic distribution in the United States, virtually no human transmission is believed to occur in the majority of the United States (outside of Texas). The occurrence of 9 cases of Leishmania mexicana cutaneous leishmaniasis was described at the end of 2007. While endemic human leishmaniasis remains most common in Texas, isolated cases have been reported as far north as Pennsylvania, with no associated travel outside the patient’s home.

International

Leishmaniasis occurs in temperate and tropical climates in all parts of the world except Australia and Oceania (ie, Pacific islands of Melanesia, Micronesia, and Polynesia). Leishmaniasis is known to exist in at least 88 different countries, with at least 350 million people at risk of acquiring the disease. The vast majority of cutaneous leishmaniasis cases occur in Afghanistan, Algeria, Brazil,^[3] Peru, Iran, Iraq, Syria, and Saudi Arabia, whereas most visceral leishmaniasis cases occur in India, Bangladesh, Nepal, Brazil, and the Sudan.^[4] The sandfly vector is adept at adjusting to climatic changes and to pressures of human habitation; therefore, vigilant epidemiologic tracking is required to monitor new patterns of disease prevalence.^[5]

Mortality/Morbidity

As many as 90% of localized cutaneous forms of leishmaniasis from several parts of the world heal spontaneously with minimal scarring. This is not to say that the disease is without morbidity, especially in areas where even minimal facial disfiguring can condemn young girls to life without the prospect of marriage or acceptance in society. Even worse, these are areas of the world that have the highest burden of disseminated, recidivans, and post–kala-azar forms of cutaneous leishmaniasis. These forms can be exceedingly disfiguring cosmetically because of the degree of persistent involvement; however, these forms are not life threatening.

See the image below.

Mucocutaneous disease affecting the mucous membranes of the mouth, nose, and soft palate is especially debilitating and destructive. Found only in the New World and principally in South America, mucocutaneous leishmaniasis can result in extensive midfacial mutilation and, occasionally, death resulting from airway or nutritional compromise.

Visceral leishmaniasis (kala-azar) is a serious, potentially lethal systemic illness. Epidemics of kala-azar in impoverished communities can result in death in the majority of untreated patients. The fairly significant asymptomatic-to-symptomatic ratio varies from approximately 19:1 to even higher in some studies. The disease tends to affect individuals in poor states of health, with poor nutritional status, and with even the most minor decreased immune status much more severely than individuals with good health, good nutritional status, and intact immune systems.

For some of the same reasons, kala-azar also affects young children much more severely than older children and adults. Almost all visceral leishmaniasis infections, for example in Iraq, occur in children younger than 5 years and the most occur children younger than 1 year. Additionally, a well-described and feared interaction is kala-azar in combination with HIV infection, which leads to more severe and rapidly progressive fatal outcomes from both diseases acting synergistically.

Race

No racial preferences are recognized or described. Some minor associations with various racial groups have been noted, but these are confounded by and a result more strongly associated with occupational exposure.

Sex

No clear sex predilections are recognized; however, the prevalence is slightly higher in men than in women in most epidemiologic studies, possibly as a result of occupational contact with the sandfly vector.

Age

No specific age susceptibility is known for infection with Leishmania species in general; however, individuals at the extremes of age may be less able to mount effective immune responses to infection and therefore manifest clinical disease more often, especially seen in association with visceral leishmaniasis.

Leishmania infantum infection has long been thought to be associated with an infantile form of visceral leishmaniasis, which can have devastating outcomes for children, particularly for those younger than 1 year. This apparent predilection for the young appears to occur in highly endemic areas because of what may be protective immunity reducing the risk of reinfection in adults.

Clearly, in some parts of the world, Leishmania donovani is a much more devastating disease in older children.