Dermatologic Manifestations of Leishmaniasis Clinical Presentation

The discovery of parasites in lesions of cutaneous leishmaniasis or visceral leishmaniasis was reported in the late 1800s and early 1900s. By the mid 1900s, the transmission and life cycle of the Leishmania organism had been scientifically confirmed. Since that time, many clinical syndromes and numerous (at least 20) morphologically similar species and subspecies of the protozoan have been, and continue to be, discovered. The taxonomy of Leishmania organisms is complex, and no single categorization is generally accepted.

The 2 simplest and most widely used disease categorization systems are based on clinical disease and geographic occurrence, as follows:

• Clinical disease: The 3 primary clinical forms of leishmaniasis are cutaneous, mucocutaneous, and visceral disease. Cutaneous leishmaniasis can be further divided into localized, diffuse cutaneous, recidivans, and post–kala azar dermal leishmaniasis.
• Geographic occurrence: Old World leishmaniasis is caused by Leishmania species found in Africa, Asia, the Middle East, the Mediterranean, and India, and it produces cutaneous or visceral disease. New World leishmaniasis is caused by Leishmania species found in Central America and South America, and it produces cutaneous, mucocutaneous, and visceral disease.

The following forms of leishmaniasis have been identified:

• Localized cutaneous leishmaniasis: Crusted papules or ulcers occur several weeks to months (in rare cases) after sandfly bite inoculation on exposed skin. Lesions may be associated with sporotrichotic spread and usually heal spontaneously.
• Diffuse cutaneous leishmaniasis: Analogous to lepromatous leprosy, individuals with diffuse cutaneous leishmaniasis cannot mount a cell-mediated immune response to the Leishmania parasite. Consequently, patients develop multiple, widespread cutaneous papules and nodules, and they are anergic to leishmanin skin testing (LST).
• Recidivans cutaneous leishmaniasis: A relatively uncommon clinical variant of leishmaniasis, recidivans cutaneous leishmaniasis appears as a recurrence of lesions at the site of apparently healed disease years after the original infection. Recidivans cutaneous leishmaniasis lesions typically occur on the face, and recidivans cutaneous leishmaniasis manifests as an enlarging papule, plaque, or coalescence of papules that heals with central scarring. Relentless expansion at the periphery may cause significant facial destruction similar to the lupus vulgaris variant of cutaneous tuberculosis.
• Post–kala azar dermal leishmaniasis: Endemic to India and the Sudan, this form of leishmaniasis develops months to years after the patient's recovery from visceral leishmaniasis. Cutaneous lesions demonstrate great variability, ranging from hypopigmented macules to erythematous papules and from nodules to plaques. As in leprosy, the wide clinical spectrum of post–kala azar dermal leishmaniasis reflects the immune response of the individual to the Leishmania organism. Lesions may be numerous and persist for decades. Isolated parasites from the lesions are identical to those that cause the original visceral disease.
• Mucocutaneous leishmaniasis: Predominantly a New World disease, this form of leishmaniasis may not manifest clinically until years after localized cutaneous disease apparently has healed. In a poorly understood manner, certain species of Leishmania migrate to the upper respiratory tract, where relentless destruction of the oropharynx and nose ensues. Gradually, the migration results in extensive midfacial destruction and, occasionally, in death.
• Visceral leishmaniasis (kala azar): Leishmania parasites localize to the reticuloendothelial system, rather than to the skin, and produce a potentially lethal widespread systemic disease.

Localized cutaneous leishmaniasis usually manifests as a nonspecific ulcer that can mimic many other infectious and noninfectious skin conditions. The vast majority of cases patients spontaneously with scarring and never come to the attention of clinicians. Even in US troops stationed in Iraq, it is currently felt, by many most closely associated with the disease and familiar with the epidemiology in the military, that less than 25% of all disease ever concerns afflicted soldiers enough to seek medical attention.

In both the localized cutaneous and mucocutaneous forms of leishmaniasis, cell-mediated immunity to the parasite is vigorous and organism density in the skin and/or mucosa is low, especially in long-standing disease (although very early in the disease large numbers of the parasites are frequently found). Therefore, growing organisms in culture can be difficult, as can finding them in pathological specimens. Malnourished individuals are at greater risk of acquiring leishmaniasis and respond less well to treatment than those with adequate nutrition.

The general consensus is that less than 5% of individuals infected by Leishmania brasiliensis, and a smaller percentage of individuals infected by Leishmania panamensis and Leishmania guyanensis, develop mucosal metastases several months to years after the apparent resolution of cutaneous disease. However, no rigorous studies prove this commonly accepted rate. Without treatment though, even in this small number, destruction of the oral and nasopharyngeal mucosa can be quite devastating and relentless. Symptoms of visceral leishmaniasis can be confused with many other infectious diseases; however, in endemic areas, the typical patient has wasting and presents with massive splenomegaly, pancytopenia, hypergammaglobulinemia, and intermittent fevers (although they are less acutely ill than patients with malaria).

A typical lesion of localized cutaneous leishmaniasis begins as an inflammatory papule, which later progresses to an ulcer. This may be associated with sporotrichotic lymphatic spread. In the vast majority of cases, the ulcers heal spontaneously with scarring.

See the images below.

Patients with diffuse cutaneous leishmaniasis develop hundreds of papules, nodules, and plaques throughout the skin in a clinical picture that can be reminiscent of lepromatous leprosy. This form of leishmaniasis often is resistant to therapy and may assume a chronic course.

See the image below.

In recidivans cutaneous leishmaniasis, typically, psoriasiform plaques occur on the face and progress centrifugally, bearing a striking resemblance to lupus vulgaris. Similar to disseminated disease, recidivans cutaneous leishmaniasis may be resistant to therapy and result in a disfiguring clinical picture.

See the image below.

In post–kala azar dermal leishmaniasis, cutaneous lesions are polymorphous, ranging from hypopigmented or erythematous macules to papules and nodules that may coalesce. Similar to diffuse cutaneous leishmaniasis, post–kala azar dermal leishmaniasis closely resembles lepromatous leprosy. Prolonged intensive treatment is required to treat this disfiguring, but usually not lethal, form of leishmaniasis.

See the image below.

When left untreated, mucocutaneous leishmaniasis gradually spreads and results in extensive midfacial mutilation or, in some cases, in death.

See the images below.

The hallmarks of visceral leishmaniasis are fever, malaise, hepatosplenomegaly, anorexia, wasting, pancytopenia, and hypergammaglobulinemia. Occasionally, the skin becomes severely xerotic and hyperpigmented because of melanocyte stimulation. This form of leishmaniasis frequently is lethal if not treated.

See the image below.

In the vast majority of cases, sandfly bites transmit leishmaniasis; however, infection potentially may be transmitted via a congenital route, through blood transfusions, or through contaminated needle sticks. Clear documentation of the potential of transfusion-associated leishmaniasis exists, although clear documentation of the actual occurrence of transfusion-related disease is less certain because most cases in the literature occur in endemic areas of the world.^{[6, 7]}

The different clinical manifestations and the commonly associated parasite species are listed below. Importantly, however, variation in these general associations often occur.

• Cutaneous leishmaniasis

  • Localized cutaneous leishmaniasis
    • Old World -Leishmania major, Leishmania tropica, Leishmania aethiopica, and L infantum
    • New World – L mexicana, Leishmania venezuelensis, Leishmania amazonensis, L braziliensis, L panamensis, L guyanensis, Leishmania peruviana, and L eishmania chagasi
  • Diffuse cutaneous leishmaniasis
    • Old World – L aethiopica
    • New World – L mexicana, L amazonensis, and L venezuelensis
  • Recidivans cutaneous leishmaniasis
    • Old World – L tropica
    • New World – L braziliensis
  • Post–kala azar dermal leishmaniasis
    • Old World – L donovani and L infantum
    • New World – L chagasi
• Mucocutaneous leishmaniasis

  • New World – L mexicana, L amazonensis, L braziliensis, L guyanensis, and L panamensis
• Visceral leishmaniasis

  • Old World – L infantum, L donovani, and L tropica (rare; also may produce the atypical viscerotropic disease)
  • New World – L chagasi

Other diagnostic considerations

The differential diagnosis of localized cutaneous leishmaniasis is extensive and includes impetigo, pyoderma gangrenosum, deep fungal infection, mycobacterial infection, sarcoidosis, and squamous cell carcinoma.

Diffuse cutaneous leishmaniasis and post–kala azar dermal leishmaniasis closely resemble lepromatous leprosy. Recidivans cutaneous leishmaniasis may mimic cutaneous tuberculosis (lupus vulgaris, tuberculosis verrucosa cutis), psoriasis, deep fungal infection, or nummular dermatitis. Mucocutaneous leishmaniasis may simulate paracoccidioidomycosis, histoplasmosis, syphilis, yaws, rhinoscleroma, squamous cell carcinoma, and midline granuloma of the face.

Visceral leishmaniasis may be confused with a variety of other infectious diseases or febrile systemic illnesses, including schistosomiasis, malaria, tropical splenomegaly syndrome, histoplasmosis, malnutrition, typhoid fever, brucellosis, miliary tuberculosis, lymphoma, leukemia, African trypanosomiasis, and bacterial endocarditis.

Coexisting infectious diseases and/or nutritional deficiencies may significantly impact the severity and outcome of leishmanial infection. In southern Europe, visceral leishmaniasis is emerging most notably as a serious opportunistic infection in individuals with HIV infection. Co-infection by HIV and leishmanial organisms is particularly common in southern Europe along the Mediterranean, where most adult patients (< 70%) with visceral leishmaniasis have late-stage AIDS. Individuals with HIV infection and leishmaniasis have higher parasite loads, poorer responses to skin testing, lower responses to pentavalent antimony, and higher posttreatment relapse rates than those of their immunocompetent counterparts.^[4]