Cutaneous leishmaniasis

Overview
Cutaneous leishmaniasis is the most common form of leishmaniasis. It is a skin infection caused by a single-celled parasite that is transmitted by sand-fly bites. There are about 20 species of Leishmania that may cause cutaneous leishmaniasis.

Epidemiology


Cutaneous leishmaniasis endemic to many parts of the world. Around twenty different species of Leishmania parasite are capable of infecting humans. The distribution of cutaneous leishmaniasis is very tightly linked to geography and villages even 15 miles apart can have very different rates of cutaneous leishmaniasis.

Some Leishmania species are closely linked to humans and are therefore found in cities (e.g., Leishmania tropica), whereas some are more traditionally associated with animal species and are therefore considered zoonoses (e.g., Leishmania major]). Some species that are traditionally considered zoonotic (e.g., L. panamensis) may be becoming primarily human diseases.

Pathology
Promastigotes of leishmania are transmitted to human skin by the bite of a sandfly. Leishmania then invades human macrophages and replicates intracellularly.

A raised, red lesion develops at the site of the bite (often weeks or sometimes years afterwards). The lesion then ulcerates and may become secondarily infected with bacteria. In many species (for example, Leishmania major) the lesion often spontaneously heals with atrophic scarring. In some species (for example, L. viannia braziliensis) the lesion may spontaneously heal with scarring, but then re-appear elsewhere (especially as destructive mucocutaneous lesions). Lesions of other leishmania species may spontaneously heal and then re-appear as satellite lesions around the site of the original lesion, or along the route of lymphatic drainage.

Some species tend to cause cutaneous leishmaniasis (e.g., Leishmania major and L. tropica), whereas some species tend to cause visceral leishmaniasis (e.g., Leishmania infantum and Leishmania donovani).

Post kala-azar dermal leishmaniasis
Post kala-azar dermal leishmaniasis(PKDL) is a sequel of Kala-azar that may appear on skin of affected individuals upto 20 years after the being partially treated, untreated or in those considered adequately treated. In Sudan they can be demonstrated in up to 60% of treated cases.They manifest as hypo-pigmented macules, papules, nodules, or facial erythema. Though any organism causing Kala-zar can lead to PKLD, it is commonly associated with L. donovani which gives different disease patterns in India and Sudan. In Indian variant nodules enlarge with time and form plaques but rarely ulcerate but African variety often ulcerate as they progress. Nerve involvement is common in African variety but rare in Indian subcontinent .Histology demonstrates mixture of chronic inflammatory cells; there can be macrophage or epitheloid granuloma. Parasite concentration is not consistent among studies perhaps reflecting low sensitivity of diagnostic methods used in earlier entries.

Current approach to diagnosis involves 1. demonstration of parasite by microscopy, in vitro culture or animal inoculation, 2. immuno diagnosis of parasite antigen, 3.detection of parasite DNA in tissue. Newer PCR based tools have higher sensitivity and specificity. Emergence of PKLD has been reported in HIV affected individuals and may become a problem in future.

Sodium stibogluconate (SSG) alone or in combination with rifampicin is used for the treatment of PKLD for a long course up to 4 month. Compliance can be an issue for such long course.

Mucocutaneous leishmaniasis
Mucocutaneous leishmaniasis is the most feared form of cutaneous leishmaniasis because it produces destructive and disfiguring lesions of the face. It is most often caused by Leishmania (Viannia) braziliensis, but cases caused by L. aethiopica have also been rarely described.

Treatment for mucocutaneous leishmaniasis is with the combination of pentoxifylline and a pentavalent antimonial at high-dose for 30 days: this achieves cure rates of 90%. Treatment with a pentavalent antimonial on its own fails to cure up to 42% of patients even in those patients who achieve an apparent cure, as many as 19% will relapse.

Diagnosis
Diagnosis is based on the characteristic appearance of non-healing raised, scaling lesions that may ulcerate and become secondarily infected with organisms such as Staphylococcus aureus, in someone who has returned from an endemic area. The gold standard for diagnosis is PCR.

Treatment
The evidence for optimal treatment of cutaneous leishmaniasis is patchy. Treatments that work for one species of leishmania may not work for another; it is recommended that advice of a tropical medicine or geographical medicine specialist be sought. Ideally, every effort should be made to establish the species of leishmania by molecular techniques (PCR) prior to starting treatment. In the setting of a developing country, there is often only one species present in a particular locality, so it is usually unnecessary to speciate every infection. Unfortunately, leishmaniasis is an orphan disease, and almost all the current treatment options are toxic with significant side-effects.


 * Leishmania major
 * Treatment of L. major infections are usually considered to heal spontanously and do not require treatment, but there have been several reports of severe cases caused by L. major in Afghanistan. In Saudi Arabia, a six week course of oral fluconazole 200mg daily has been reported to speed up healing.


 * Leishmania (Vianna) braziliensis
 * Treatment with pentavalent antimonials or amphotericin is mandatory, because of the risk of developing disfiguring mucocutaneous lesions.


 * Leishmania infantum
 * L. infantum is considered to be a rare cause of cutaneous leishmaniasis.

New treatment option are arising from the new oral drug Miltefosine (Impavido®) which has shown in several clinical trial to be very efficient and safe in visceral and cutanous leishmaniasis. Recent studies from Boliva show a high cure rate for mucocutaneous leishmaniasis. First comperative studies versus pentavalent antimonials in Iran and Pakistan show also a high cure rate for L.major and L.tropica. It is registered in many countries of Latin America (e.g. Colombia) as well in Germany, the home country of the originator Zentaris GmbH. In October 2006 it received orphan drug status from the US Food and Drug administration. The drug is generally better tolerated than other drugs. Main side effects are gastrointetinal disturbance in the 1-2 days of treatment which does not affect the efficacy.

Secondary bacterial infection (especially with Staphylococcus aureus) is common and may require antibiotics. Unfortunately, clinicians who are unfamiliar with cutaneous leishmaniasis may mistake the lesion for a pure bacterial infection (especially after isolation of S. aureus from bacterial skin swabs) and fail to consider the possibility of leishmaniasis.