Cutaneous leishmaniasis: Clinical manifestations and diagnosis

INTRODUCTION — Leishmaniasis consists of a complex of vector-borne diseases caused by a heterogeneous group of protozoa belonging to the genus Leishmania; it is transmitted by sand fly vectors [1]. Clinical manifestations range from cutaneous ulcers to systemic multiorgan disease. Specific organisms are frequently associated with a typical clinical picture (table 1), although this can be variable.

The clinical manifestations and diagnosis of cutaneous leishmaniasis (CL) will be reviewed here. Issues concerning treatment, epidemiology, and control are discussed separately. (See "Cutaneous leishmaniasis: Treatment" and "Cutaneous leishmaniasis: Epidemiology and control".)

CLINICAL MANIFESTATIONS — The incubation period for symptomatic CL ranges from weeks to months; mucosal involvement may occur years following initial infection [2-4]. Asymptomatic infection may occur in about 10 percent of patients; this has been suggested by delayed hypersensitivity skin testing [5].

Leishmania causes a spectrum of cutaneous disease. The range of clinical manifestations may be attributed to variability in parasite virulence (and other intrinsic characteristics) and variability in the host immune response. At one end of the spectrum, mucosal leishmaniasis (ML) and leishmaniasis recidivans (LR) are caused by oligoparasitic disease associated with a marked cellular immune response. The center of the spectrum consists of localized cutaneous leishmaniasis (LCL), which is the most common clinical presentation. At the opposite end of the spectrum, diffuse cutaneous leishmaniasis (DCL) is caused by polyparasitic disease with a predominance of parasitized macrophages and no granulomatous inflammation. This spectrum of clinical presentation and host immune response is similar to clinical manifestations observed in the setting of leprosy [6]. (See "Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

The cutaneous syndromes associated with Leishmania parasite infection include LCL, LR, DCL, and ML. These will be further described below; they are presented in order of relative clinical frequency.

Localized cutaneous leishmaniasis — Cutaneous lesions tend to occur on exposed areas of the skin; sand fly mouthparts generally cannot penetrate through clothing. Sand fly bite reactions are generally pruritic but usually do not enlarge; they may resolve slowly over weeks (even in the absence of parasitic infection).

Localized cutaneous leishmaniasis (LCL) begins as a pink-colored papule that enlarges and develops into a nodule or plaque-like lesion (often with central softening), leading to a painless ulceration with an indurated border (picture 1). In Old World CL, the ulcer is often covered with a hyperkeratotic eschar (picture 2). In New World CL, the ulcer may be covered with thick white-yellow fibrinous material (picture 3).

Multiple lesions may be present. The clinical appearance can be variable and may include sporotrichoid, verrucous, zosteriform, psoriaform, eczematous, and/or erysipeloid features [7]. Small satellite lesions may develop just outside the plaque/ulcer. Spread of lesions along the draining lymphatics may be observed; these may or may not ulcerate but can be palpated subcutaneously and proximally along the lymphatic chain leading from the primary lesion (nodular lymphangitis). Regional adenopathy can occur and may be prominent in some cases [8].

Secondary bacterial infection of the ulcer may occur and may be associated with purulent drainage and local cellulitis. Bacterial superinfection may lead to enlargement of the primary lesion and contribute to its persistence.

The natural history of LCL consists of gradual healing over months to years; the time varies depending on the species and lesion size [7,9]. Leishmaniasis heals with an atrophic, depressed scar; it can also heal as a keloid (in patients predisposed to keloid scarring). Following resolution of the initial lesion(s), it is possible that reactivation of the initial lesion(s) may develop during the subsequent year (or later for ML).

There are some distinguishing clinical features between species, although significant overlap may occur; speciation should not be based solely on clinical manifestations.

●L.L. major infection (Old World CL) typically has a short incubation period, and ulcers may expand in one to two months to ≥6 cm in diameter. Multiple lesions are common. Frequently, ulcers are covered with a thick crust, and nodular, plaque-like lesions are common. Epithelialization of the ulcer bed usually occurs within six months.

●L.L. tropica infection (Old World CL) is typically a more chronic infection than CL due to L.L. major; it evolves over months to years. The skin lesions are relatively few in number and sometimes relatively small (1 to 2 cm). Facial lesions may be larger, and a predilection for the nose and forehead may be observed. The lesions are very dry and appear crusted. Spontaneous resolution is slow, usually over one to two years or longer. L.L. tropica can be associated with the complication of LR. (See 'Leishmaniasis recidivans' below.)

●L.L. aethiopica infection (Old World CL) usually consists of a solitary facial lesion with or without surrounding satellite papules, which coalesce into spreading nodules or plaques. Lesions may spread along mucocutaneous margins but do not involve the oral or nasal mucosa. L.L. aethiopica is associated with relatively long chronicity. Histologically, relatively little inflammation is seen.

●L.L. infantum-chagasi infection can cause a small number of slow-growing nodular lesions that persist for years. This is an Old and New World species most often associated with visceral leishmaniasis, but it can also cause CL; its presence in the skin does not imply coexistent visceral disease.

●L.L. mexicana (New World CL) infection generally produces small, chronic skin ulcers, usually one or few in number. Lesions on the ear are called "Chiclero's ulcer," which reflects the biting habits of the sand fly vector. L.L. mexicana lesions may spontaneously heal relatively quickly; one study noted 88 percent of lesions healed by 14 weeks [9].

●L.V. braziliensis (New World CL) infection causes large lesions, frequently with lymphocutaneous involvement. A sporotrichoid pattern of multiple ulcers or nodular lymphangitis is common (picture 1). Lymphadenopathy, fever, and malaise may precede development of any lesion [10]. Ulcers may heal in 6 to 12 months but can be quite persistent [11]. L.V. braziliensis CL may be associated with mucosal leishmaniasis concurrently or subsequently. Disseminated CL due to L.V. braziliensis appears to be emerging in northeast Brazil [12].

Differential diagnosis — The differential diagnosis of LCL includes bacterial infection, cutaneous myiasis, pyoderma gangrenosum, ecthyma, impetigo, cutaneous malignancy, sarcoidosis, prurigo nodularis, lichen simplex chronicus, spider bite, tropical ulcer, yaws, cutaneous anthrax, nocardia and actinomycosis, cutaneous tuberculosis, nontuberculous mycobacteria such as Mycobacterium marinum, M. fortuitum, and less likely Buruli ulcer (M. ulcerans), and fungal infections such as sporotrichosis, blastomycosis, and chromoblastomycosis.

Clinical features that may help differentiate CL from these entities include its chronicity, general painlessness, frequent clustering of lesions, occurrence on an exposed location, and orientation of skin lesion along skin creases. Other important distinguishing characteristics include the presence of inflammatory satellite papules, subcutaneous induration beneath lesion, ulcerations with well-defined indurated borders, and presence of subcutaneous nodules [13].

Epidemiologic clues that may suggest leishmaniasis include that most individuals with leishmaniasis are otherwise healthy, cases may cluster (several individuals in an exposed group may have skin lesions), some patients recall small insect bites, exposure is usually in rural areas dusk to dawn during the warmer months, risk is usually recent travel or residence in leishmaniasis-endemic regions, and incubation period is typically several weeks to a few months.

Minor trauma with exposure to brackish water suggests M. marinum. Persistent pruritus is consistent with the chronic sequelae of insect bites. Initial minor skin trauma on extremities in gardeners or farmers is suggestive of sporotrichosis. Animal-to-human transmission of sporotrichosis can occur via chronic ulcerative lesions. Wood cutters with no footwear in tropical forests with high rainfall in South America and Madagascar are at risk for chromoblastomycosis. Immunocompromised hosts may have cutaneous tuberculosis or rapid-growing nontuberculous mycobacterial skin lesions.

Leishmaniasis recidivans — Leishmaniasis recidivans (LR) refers to a relatively uncommon syndrome caused by L.L. tropica infection. Following healing of the primary lesion, persistent organisms can cause new papules to form around the margin of the scar. Skin biopsy demonstrates few parasites but a robust granulomatous, cell-mediated immune response. LR can occur following trauma in the area of a prior lesion many years after initial healing [14].

Diffuse cutaneous leishmaniasis — Diffuse cutaneous leishmaniasis (DCL) is a rare syndrome that occurs mainly in the setting of L.L. aethiopica, L.L. mexicana, and L.L. amazonensis infection. It begins as a localized lesion that does not ulcerate; rather, amastigotes disseminate to macrophages in other areas of the skin. In general, soft nodules or plaques form on the face and extensor limb surfaces, but the entire body may be involved. Histologically, many parasites are seen, but there is scarce lymphocytic reaction. Patients with DCL usually have a defect in the cell-mediated immune response and are anergic to Leishmania antigen. DCL due to L.L aethiopica is associated with high rates of ML [15]. DCL reported in acquired immunodeficiency syndrome (AIDS) patients has involved other parasites species such as L.L. major and L.V. guyanensis [16]. Successful treatment of DCL is difficult.

Mucosal leishmaniasis — Mucosal leishmaniasis (ML), also known as espundia, occurs in the New World and is caused by the Viannia subgenus, especially L.V. braziliensis, L.V. guyanensis, and L.V. panamensis, but also L.L. amazonensis (figure 1) [17]. ML due to Old World species L.L. infantum and L.L. aethiopica has been described among immunocompromised hosts (see 'CL in immunocompromised hosts' below). Rarely, L.L. tropica, L.L. major, L.L donovani, and L.L. infantum-chagasi mucosal leishmaniasis are reported [18,19].

The risk of ML due to L.V. braziliensis infection is higher in South America (particularly Bolivia, Peru, and Brazil) than in Central America, specifically north of Costa Rica. Overall, the risk of mucosal disease following a primary CL lesion is less than 10 percent; in some reports, it has been close to 30 percent [20]. ML can occur concurrently or following partially treated or untreated CL. Concurrent ML has been described in up to 28 percent of cases; subsequent ML can occur up to 10 years or more following CL [21].

ML is characterized by mucosal destruction. Symptoms include nasal stuffiness or blockage, mucosal bleeding, increased secretions, and sloughing of dead tissue. Some have pain, deformity, and inflammation (picture 4). Erosion of mucosal surfaces occurs, most commonly in the nose, mouth, or nasal septum (eg, in the form of cartilage perforation). Other involved areas may include the cheek, pharynx, palate, epiglottis, larynx, trachea, and genitalia. Hoarseness and/or a brassy cough are suggestive of laryngeal involvement. The disease is considered mild in the setting of isolated nasal stuffiness, moderate if there is associated odynophagia or dysphonia, and severe if there is respiratory distress or severe dysphonia.

Substantial disfigurement can result from destruction of the nasal cartilage and surrounding tissues. Rarely, aspiration, respiratory compromise, and/or death can occur. Any patient with New World CL (Viannia subgenus) regardless of nasal, oral, or hypopharyngeal symptoms should undergo visual inspection of all mucosal surfaces of the hypopharynx, including the vocal cords and oronasal pharynx. Abnormal-appearing tissue should be biopsied, and histopathology as well as polymerase chain reaction (PCR) testing for Leishmania should be performed.

Histopathology generally demonstrates a robust cell-mediated immune response, and large quantities of cytokine production, T lymphocyte proliferation, and neutrophils expressing proteinases have been observed [22]. In general, relatively few parasites are observed in mucosal lesions.

Leishmania RNA virus 1 (LRV1), an endosymbiont of L.V. guyanensis and some L.V. braziliensis organisms, may augment infection and may also be associated with metastatic involvement. It acts as an immunogen and elicits a hyperinflammatory immune response through toll-like receptor 3 (TLR3) [23].

CL in immunocompromised hosts — Control of intracellular Leishmania infection requires a Th1-dependent cell-mediated immune response including cells (CD4 and CD8 T cells, natural killer, dendritic cells, macrophages) and cytokines (interferon-gamma, tumor necrosis factor-alpha, interleukin-12).

Patients with immunosuppressing conditions are at increased risk for more severe cutaneous leishmaniasis (CL). This includes patients on chronic corticosteroids, biologic modulators, or other immunosuppressive drugs; organ transplant recipients; pregnant patients; and patients with HIV/AIDS:

●Reactivation of CL and dissemination or progression to ML has been noted after chronic corticosteroid use. It has also been observed that application of topical steroids to CL lesions leads to increased numbers of amastigotes on skin biopsy, suggesting that corticosteroids may contribute to local disruption of immune regulation [24,25].

●Biologic immunomodulators (such as infliximab) have been associated with both primary and reactivation CL [26].

●CL is relatively unusual among organ transplant recipients; it has been observed in the Mediterranean region with onset long after transplant (median 18 months, range 6 to 19 months) [27]. Other relatively unusual observations include a case of DCL due to L.L. major (a species not usually associated with dissemination outside the skin) and some CL cases with multiple lesions consisting of nodular rather than ulcerative appearance [27,28].

●HIV-induced immunosuppression has been associated with CL primary infection as well as reactivation, since Leishmania parasites are capable of persisting in scars of prior lesions [29]. CL in patients with HIV/AIDS has also been associated with disseminated disease, especially in the setting of CD4 <200/mm³. Manifestations include disseminated CL due to L.L. major, rapid progression of New World CL to ML, and ML due to L.L. infantum-chagasi. Patients with AIDS may be less responsive to treatment than other patients and may require therapy for suppression of CL infection until immune reconstitution occurs. Such patients are also at risk for immune reconstitution inflammatory syndrome (IRIS) [30-32].

●Pregnancy >18 weeks has been associated with large (up to 6 cm²), exophytic, "cauliflower-like" CL lesions [33,34]. Obesity has also been associated with this finding [35].

DIAGNOSIS

Clinical approach — The diagnosis of CL should be considered in patients with one or more chronic skin lesions and a history of exposure in an area where leishmaniasis is endemic [36]. Definitive diagnosis requires demonstration of the parasite in a clinical specimen (usually skin) by histology, culture, or molecular analysis via polymerase chain reaction (PCR). To maximize diagnostic yield, ideally all three diagnostic tests are warranted on the initial sample if feasible. If not all tests can be performed, then histology and PCR may provide sufficient information. Parasitologic diagnosis to the level of the Leishmania species should be pursued, since this information may influence determination of treatment [1]. Metagenomic next-generation sequencing (NGS) is also used for diagnosis [37,38].

Reference laboratory support is available; laboratories should be contacted before diagnostic samples are obtained to obtain instructions and transport media. In the United States, the Centers for Disease Control and Prevention (CDC) offers diagnostic services (email [email protected]). The CDC Parasitic Disease Public Inquiries may be contacted at 404-718-4745 (email [email protected]). The University of Washington Molecular Diagnosis Microbiology Section offers molecular testing for genus and species identification (email [email protected]). The Walter Reed Army Institute of Research also provides diagnostic services for military and veteran patients and may be contacted at 240-595-7353. In Canada, the National Reference Centre for Parasitology offers diagnostic support.

Clinical history — The clinical history should include an explicit travel history as well as questioning whether fellow travelers have developed similar lesions. Patients should be asked to comment on the duration of the skin lesions, whether they are painful (not typical of leishmaniasis), and whether they have progressed or improved. The history should also elicit the presence of nasal symptoms, comorbid medical conditions, prior treatment, and concurrent medications (particularly immunosuppressing ones) [1]. In addition, ascertaining the patient's level of concern about the skin lesions can be helpful for guiding treatment decisions.

Physical examination — Physical examination should include a complete skin examination and careful evaluation of the anterior nares, septum, and oropharynx. Palpate along the lymphatic chains cephalad to lesions for subcutaneous nodules, gently palpate the lesion for tenderness and induration, and check for regionally draining lymph node enlargement. It can be helpful to measure and obtain photographs of skin lesions to assess progress over time.

Referral to a specialist for endoscopic otorhinolaryngologic examination is reasonable for patients with risk for mucosal leishmaniasis (such as those with epidemiologic exposure in South America) who have symptoms and/or signs of mucosal involvement or who have no symptoms or signs but thorough nasopharyngeal examination is not possible.

Specimen collection — Specimens should be collected from lesions that appear active and ulcerative, without evidence of secondary infection [1]. The lesion should be cleaned gently with soap and water or povidone-iodine and then washed with saline; residual iodine and/or ethanol should be avoided if culture is planned. Remove any hyperkeratotic eschar. The base and margins of ulcerative lesions should be scraped gently with a sterile scalpel blade or lancet or brushed with a cytology brush. Touch impressions using tape or a glass slide touched to the ulcer may also provide diagnostic samples. The tissue collected should be submitted for histology, culture, and PCR.

Nodular lesions, plaque-like lesions, and lesions on the face (or other sensitive areas) may be sampled via injection and withdrawal of small amounts of nonbacteriostatic normal saline at three to five sites. Some perform the aspiration without saline and obtain a tiny drop of aspirate in the hub of a 1 mL syringe, using a fine needle with rotary motion in lesion border. The aspirate may be submitted for culture and PCR. An alternative technique for sample collection consists of skin snips of the indurated margins of a lesion.

A full-thickness punch biopsy of the skin (4 to 5 mm) allows evaluation of histology and cellular response; it may also be submitted for culture to evaluate for leishmaniasis, acid-fast mycobacteria, and fungi. The preferred site for skin biopsy is the raised border of an ulcerative lesion (picture 3). Following biopsy, the sample should be gently blotted and then touched to a clean glass slide for multiple "touch prep" smears (see 'Histopathology' below). Excisional biopsies of skin lesions are not appropriate as recurrence may be seen along the suture line.

Diagnostic tools — Diagnostic methods include visualization of the characteristic amastigote in smears or tissue (histopathology), parasite isolation by in vitro culture, and molecular detection of parasite DNA [1]. It is reasonable to pursue multiple diagnostic approaches to maximize the likelihood of a positive result, in conjunction with the expertise of a reference laboratory. Molecular amplification assays are the most sensitive tests available for diagnosis of CL (see 'Molecular techniques' below).

Histopathology — The Leishmania amastigote is an oval to round organism 1.5 to 4.0 microns in diameter with a distinct cell membrane, cytoplasm, internal nucleus, and rod-shaped kinetoplast containing mitochondrial DNA (picture 5). Visualization of the kinetoplast is essential for a histologic diagnosis. This may require viewing several different sections in fixed tissue samples. Giemsa staining is typically used; with this stain, the cytoplasm is blue, the nucleus violet-blue, and the kinetoplast red to violet (a critical diagnostic characteristic). These findings may be observed on histology or touch prep smears.

A tissue Gram stain can be useful to highlight the kinetoplast in tissue samples, although hematoxylin and eosin staining is usually sufficient. Under oil immersion (100x), the parasites are found in macrophages in the upper dermis and are often surrounded by dermal chronic inflammation with lymphocytes, macrophages, plasma cells, and sometimes necrotizing granulomas. Organisms may be scarce in chronic lesions such as leishmaniasis recidivans (LR) and L.V. braziliensis infections.

Culture — In appropriate culture media, tissue amastigotes may be converted to promastigotes. In one study including 202 skin lesions comparing diagnostic methods for CL in Peru, culture and smear were less useful for skin lesions of a duration <3 months or >12 months or for nonulcerative lesions [39].

Typical liquid media consists of Schneider's drosophila media supplemented with calf serum, or Novy, MacNeal, Nicolle (NNN) media. Leishmania grows best at 26°C; the rate of growth depends on the number of parasites in the tissue, species growth characteristics, and absence of secondary bacterial contamination from the skin (which can overgrow the culture).

Expansion of the parasite in culture permits speciation using isoenzyme electrophoretic patterns or molecular techniques [40,41]. Direct staining of cultured parasites or tissues with monoclonal antibodies can also be performed in some laboratories. These methods are slow since they require growth of the promastigote Leishmania form, and therefore species identification is not always available in a clinically useful timeframe. Molecular species identification is faster but less well-studied. Matrix-assisted laser desorption/ionization (MALDI) is a more rapid method that correlates well with conventional multilocus sequence typing, but it still requires an initial parasite expansion in culture step [42].

Culture for acid-fast bacilli and fungi may also be pursued to evaluate potential alternative diagnoses.

Molecular techniques — Polymerase chain reaction is one of the most sensitive diagnostic tests for CL. High-performance characteristics have been reported compared with histology, culture, and smear [39,43]. It is important to note that PCR targets and assays vary. In one study including 202 skin lesions comparing diagnostic methods for CL in Peru, PCR had the greatest sensitivity irrespective of lesion characteristics [39]. False-negative results can occur due to technical issues or inhibitors in the sample.

The sensitivity and specificity of the SMART Leish PCR for the genus assay are 99 and 67 percent, respectively. The genus real-time PCR (RT-PCR) can detect at least four genome copies of Leishmania DNA [44]. The sensitivity and specificity of the SMART Leish-L. major assay for the species assay are 95 and 91 percent, respectively. RT-PCR has also been used for identification of Leishmania species [45,46].

Leishmania DNA has been detected in scars of New World clinically-healed lesions years following treatment [47-49].

Other assays

Serology — There is no clinical role for commercially available serology in the diagnosis of CL; the sensitivity and specificity are variable, and antibody levels are generally low. Most serologic assays cannot reliably distinguish between present and past infection. The sensitivity of serology may be higher in the setting of mucosal leishmaniasis (ML), and antibodies may decrease after treatment [50].

Serologic tests for visceral leishmaniasis can be cross-reactive in the setting of CL; these include the rK39 antibody test, such as the KalazarDetect rapid test and enzyme-linked immunosorbent assay [51].

Skin test — The Montenegro or Leishmaniasis skin test has been evaluated in research studies and is used in South America, though no preparation has been approved for human use in the United States. The test consists of intradermal injection of killed promastigotes; it is positive in 82 to 89 percent of cases of localized CL [52]. The test is read 48 or 72 hours after intradermal injection; ≥5 mm induration is considered positive. The test cannot distinguish between active and resolved infection.

An interferon-gamma release assay for leishmaniasis has been developed for epidemiologic purposes but is not commercially available [53].

DIFFERENTIAL DIAGNOSIS — Conditions that may mimic CL are summarized below; in general, the diagnoses are distinguished by histopathology and culture.

●Fungal infection – A number of fungal infections present with cutaneous lesions resembling leishmaniasis; these include histoplasmosis and coccidioidomycosis. (See "Pathogenesis and clinical manifestations of disseminated histoplasmosis" and "Primary pulmonary coccidioidal infection".)

●Sporotrichosis occurs following cutaneous inoculation and presents with lymphocutaneous spread; in rare cases, pulmonary involvement may be observed. (See "Clinical features and diagnosis of sporotrichosis".)

●Mycobacterial infection – Cutaneous tuberculosis and atypical mycobacterial infection may present with skin lesions resembling CL. (See "Cutaneous manifestations of tuberculosis" and "Overview of nontuberculous mycobacterial infections".)

●Leprosy – The dermatological manifestations of leprosy may overlap with the array of manifestations that occur in CL. Neuropathy occurs in the setting of leprosy but not in the setting of CL. (See "Leprosy: Epidemiology, microbiology, clinical manifestations, and diagnosis".)

●Skin cancer – Leishmaniasis can mimic the appearance of squamous cell carcinoma; these are distinguished by histopathology. (See "Cutaneous squamous cell carcinoma (cSCC): Clinical features and diagnosis".)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Leishmaniasis".)

SUMMARY

●Clinical manifestations

•Leishmania causes a spectrum of cutaneous disease. Mucosal leishmaniasis (ML) and leishmaniasis recidivans (LR) are caused by oligoparasitic disease associated with a marked cellular immune response. Diffuse cutaneous leishmaniasis (DCL) is caused by polyparasitic disease with a predominance of parasitized macrophages and no granulomatous inflammation. The center of the spectrum consists of localized cutaneous leishmaniasis (LCL), which is the most common clinical presentation. (See 'Clinical manifestations' above.)

•LCL consists of cutaneous lesions on exposed areas of the skin. It begins as a pink-colored papule that enlarges and develops into a nodule or plaque-like lesion (often with central softening), leading to a painless ulceration with an indurated border (picture 1). In Old World cutaneous leishmaniasis (CL), the ulcer is often covered with a hyperkeratotic eschar (picture 2). In New World CL, the ulcer may be covered with thick white-yellow fibrinous material (picture 3). (See 'Localized cutaneous leishmaniasis' above.)

•Patients with immunosuppressing conditions are at increased risk for more severe CL. These groups include patients on chronic corticosteroids, biologic modulators, or other immunosuppressive drugs, organ transplant recipients, pregnant patients, and patients with HIV/acquired immunodeficiency syndrome (AIDS). (See 'CL in immunocompromised hosts' above.)

●Diagnosis – The diagnosis of CL should be considered in patients with one or more chronic, usually painless, skin lesions and a history of exposure in an area where leishmaniasis is endemic. Definitive diagnosis requires demonstration of the parasite in a clinical specimen (usually skin) by histology, culture, or molecular analysis via polymerase chain reaction (PCR). Parasitologic diagnosis to the level of the Leishmania species should be pursued if feasible, since this information may influence determination of treatment. (See 'Diagnosis' above.)

ACKNOWLEDGMENTS — The UpToDate editorial staff acknowledges Karin Leder, MBBS, FRACP, PhD, MPH, DTMH and Peter F Weller, MD, MACP, who contributed to an earlier version of this topic review.

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