Cutaneous leishmaniasis
Encyclopedia
Leishmaniasis
Leishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly...
. It is a skin infection caused by a single-celled parasite that is transmitted by sandfly
Phlebotominae
Members of the subfamily Phlebotominae are known outside of the United States by the name sand fly. This subfamily includes numerous genera of blood-feeding flies, including the primary vectors of leishmaniasis, bartonellosis and pappataci fever...
bites. There are about 20 species of Leishmania
Leishmania
Leishmania is a genus of Trypanosomatid protozoa, and is the parasite responsible for the disease leishmaniasis. It is spread through sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Their primary hosts are vertebrates; Leishmania commonly infects...
that may cause cutaneous leishmaniasis.
Post kala-azar dermal leishmaniasis
Post kala-azar dermal leishmaniasis (PKDL) is a recurrence of Kala-azar that may appear on the skin of affected individuals up to 20 years after being partially treated, untreated or even in those considered adequately treated. In SudanSudan
Sudan , officially the Republic of the Sudan , is a country in North Africa, sometimes considered part of the Middle East politically. It is bordered by Egypt to the north, the Red Sea to the northeast, Eritrea and Ethiopia to the east, South Sudan to the south, the Central African Republic to the...
they can be demonstrated in up to 60% of treated cases. They manifest as hypo-pigmented macules, papules, nodules
Nodule (medicine)
For use of the term nodule in dermatology, see Nodule In medicine, a nodule refers to a relatively hard, roughly spherical abnormal structure....
, or facial erythema
Erythema
Erythema is redness of the skin, caused by hyperemia of the capillaries in the lower layers of the skin. It occurs with any skin injury, infection, or inflammation...
. Though any organism causing Kala-azar can lead to PKDL, it is commonly associated with L. donovani
Leishmania
Leishmania is a genus of Trypanosomatid protozoa, and is the parasite responsible for the disease leishmaniasis. It is spread through sandflies of the genus Phlebotomus in the Old World, and of the genus Lutzomyia in the New World. Their primary hosts are vertebrates; Leishmania commonly infects...
which gives different disease patterns in India
India
India , officially the Republic of India , is a country in South Asia. It is the seventh-largest country by geographical area, the second-most populous country with over 1.2 billion people, and the most populous democracy in the world...
and Sudan. In the Indian variant, nodules enlarge with time and form plaques but rarely ulcerate, but nodules from the African variety often ulcerate as they progress. Nerve involvement is common in African variety but rare in Indian subcontinent. Histology demonstrates a 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 of up to 4 months. Compliance can be an issue for such a 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.Mucocutaneous leishmaniasis is treated with long courses (e.g. 30 days) of pentavalent antimonial
Pentavalent antimonial
Pentavalent antimonials are a group of compounds used for the treatment of leishmaniasis. They are also called pentavalent antimony compounds.-Types:...
s in a high dose (20 mg/kg). This may fail to cure up to 42% of patients. Even in those patients who achieve an apparent cure, as many as 19% will relapse. Several drug combinations with immunomodulators have been tested, for example, a combination of pentoxifylline (inhibitor of TNF-α) and a pentavalent antimonial
Pentavalent antimonial
Pentavalent antimonials are a group of compounds used for the treatment of leishmaniasis. They are also called pentavalent antimony compounds.-Types:...
at a high-dose for 30 days in a small-scale (23 patients) randomised placebo
Placebo
A placebo is a simulated or otherwise medically ineffectual treatment for a disease or other medical condition intended to deceive the recipient...
-controlled study from Brazil
Brazil
Brazil , officially the Federative Republic of Brazil , is the largest country in South America. It is the world's fifth largest country, both by geographical area and by population with over 192 million people...
achieved cure rates of 90% and reduced time to cure, a result that should be interpreted cautiously in light of inherent limitations of small-scale studies. In an earlier small-scale (12 patients) study, addition of imiquimod
Imiquimod
Imiquimod is a prescription medication that acts as an immune response modifier. It is marketed by Meda AB, Graceway Pharmaceuticals and iNova Pharmaceuticals under the trade names Aldara and Zyclara, and by Mochida as Beselna. It is also referred to as R-837.- History :The original FDA approval...
showed promising results which need yet to be confirmed in larger trials.
Pathophysiology
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
Lesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
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, L. major
Leishmania major
Leishmania major is a species of Leishmania.It is associated with zoonotic cutaneous leishmaniasis.The genome has been sequenced....
) 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., L. major
Leishmania major
Leishmania major is a species of Leishmania.It is associated with zoonotic cutaneous leishmaniasis.The genome has been sequenced....
and L.tropica
Leishmania tropica
Leishmania tropica is a species of flagellate parasites that infects humans and rodents. It can cause a disease called oriental sore which is a form of cutaneous leishmaniasis.Leishmania tropica is a single-celled trypanosome parasite responsible for causing cutaneous Leishmaniasis.[1]...
), whereas some species tend to cause visceral leishmaniasis (e.g., L. infantum
Leishmania infantum
Leishmania infantum is the causative agent of infantile visceral leishmaniasis in the Mediterranean region of the Old World and in Latin America, where it has been called Leishmania chagasi. It is also an unusual cause of cutaneous leishmaniasis. Wild canids and domestic dogs are the natural...
and L donovani
Leishmania donovani
Leishmania donovani is a species of Leishmania. It is an important cause of visceral leishmaniasis. The reference genome of L. donovani extracted in the south eastern Nepal was published in 2011...
), though emerging research (due to high deployment rates of western countries to indigenous areas) is showing these species specific presentation lines are blurring .
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 PCRPolymerase chain reaction
The polymerase chain reaction is a scientific technique in molecular biology to amplify a single or a few copies of a piece of DNA across several orders of magnitude, generating thousands to millions of copies of a particular DNA sequence....
.
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
- L. major infections are usually considered to heal spontaneously and do not require treatment, but there have been several reports of severe cases caused by L. major in Afghanistan. In Saudi ArabiaSaudi ArabiaThe Kingdom of Saudi Arabia , commonly known in British English as Saudi Arabia and in Arabic as as-Sa‘ūdiyyah , is the largest state in Western Asia by land area, constituting the bulk of the Arabian Peninsula, and the second-largest in the Arab World...
, a six-week course of oral fluconazoleFluconazoleFluconazole is a triazole antifungal drug used in the treatment and prevention of superficial and systemic fungal infections. In a bulk powder form, it appears as a white crystalline powder, and it is very slightly soluble in water and soluble in alcohol. It is commonly marketed under the trade...
200 mg daily has been reported to speed up healing.
Leishmania (Viannia) braziliensis
Leishmania braziliensis
Leishmania braziliensis is a Leishmania species.It is associated with leishmaniasis.-Signs and Symptoms:Within a few months of infection, an ulcer forms. After healing there is an asymptomatic phase for three to twenty years...
- Treatment with pentavalent antimonialPentavalent antimonialPentavalent antimonials are a group of compounds used for the treatment of leishmaniasis. They are also called pentavalent antimony compounds.-Types:...
s or amphotericin is mandatory, because of the risk of developing disfiguring mucocutaneous lesions.
Leishmania infantum
Leishmania infantum
Leishmania infantum is the causative agent of infantile visceral leishmaniasis in the Mediterranean region of the Old World and in Latin America, where it has been called Leishmania chagasi. It is also an unusual cause of cutaneous leishmaniasis. Wild canids and domestic dogs are the natural...
- L. infantum causes cutaneous leishmaniasis in southern France.
New treatment options are arising from the new oral drug Miltefosine
Miltefosine
Miltefosine is a phospholipid drug.Originally developed as an antineoplastic , it is finding use as an antiprotozoal drug...
(Impavido) which has shown in several clinical trials to be very efficient and safe in visceral and cutaneous leishmaniasis. Recent studies from Bolivia show a high cure rate for mucocutaneous leishmaniasis. Comparative studies against pentavalent antimonials in Iran and Pakistan are also beginning to show 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 its developer 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 gastrointestinal disturbances 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. 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.
Epidemiology
Cutaneous leishmaniasis is 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., L. tropica
Leishmania tropica
Leishmania tropica is a species of flagellate parasites that infects humans and rodents. It can cause a disease called oriental sore which is a form of cutaneous leishmaniasis.Leishmania tropica is a single-celled trypanosome parasite responsible for causing cutaneous Leishmaniasis.[1]...
), whereas some are more traditionally associated with animal species and are therefore considered zoonoses
Zoonosis
A zoonosis or zoonoseis any infectious disease that can be transmitted from non-human animals to humans or from humans to non-human animals . In a study of 1415 pathogens known to affect humans, 61% were zoonotic...
(e.g., L. major
Leishmania major
Leishmania major is a species of Leishmania.It is associated with zoonotic cutaneous leishmaniasis.The genome has been sequenced....
). Some species that are traditionally considered zoonotic (e.g., L. panamensis) may be becoming primarily human diseases.
Cutaneous leishmaniasis has been occurring in troops coming back from Afghanistan
War in Afghanistan (2001–present)
The War in Afghanistan began on October 7, 2001, as the armed forces of the United States of America, the United Kingdom, Australia, and the Afghan United Front launched Operation Enduring Freedom...
.
See also
- List of cutaneous conditions
- Diffuse cutaneous leishmaniasis
- LeishmaniasisLeishmaniasisLeishmaniasis is a disease caused by protozoan parasites that belong to the genus Leishmania and is transmitted by the bite of certain species of sand fly...
- PhlebotominaePhlebotominaeMembers of the subfamily Phlebotominae are known outside of the United States by the name sand fly. This subfamily includes numerous genera of blood-feeding flies, including the primary vectors of leishmaniasis, bartonellosis and pappataci fever...