CONTINUING

MEDICAL EDUCATION

Cutaneous and mucocutaneous leishmaniasis Clinical perspectives Marc Z. Handler, MD,a Parimal A. Patel, MD,a Rajendra Kapila, MD,b,c,d Yasin Al-Qubati, MD,e and Robert A. Schwartz, MD, MPH, FRCP (Edin)a,c,d,f Newark, New Jersey, and Taiz, Yemen

Learning objectives After completing this learning activity participants should be able to recognize the cutaneous lesions in immigrants and travelers from endemic areas with leishmanial and delineate the modalities used in the diagnosis of the cutaneous lesions of leishmaniasis. Disclosures Editors The editors involved with this CME activity and all content validation/peer reviewers of the journal-based CME activity have reported no relevant financial relationships with commercial interest(s). Authors The authors involved with this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). Planners The planners involved with this journal-based CME activity have reported no relevant financial relationships with commercial interest(s). The editorial and education staff involved with this journal-based CME activity have reported no relevant financial relationships with commercial interest(s).

Leishmaniasis is endemic in 98 countries and territories, with 1.2 million new cases per year, making it a worldwide concern. The deadly visceral form is a leading cause of death from tropical parasitic infections, second only to malaria. Leishmaniasis appears to be increasing in many countries because of extended urbanization. The disease reservoir includes small mammals; parasite transmission occurs via bite of the female phlebotomine sandfly. Disease manifestations vary and largely depend upon the Leishmania species acquired. It may be first evident with a range of findings—from a localized cutaneous ulcer to diffuse painless dermal nodules—or, in the mucocutaneous form, ulceration of the oropharynx. In the potentially deadly visceral form, the internal organs and bone marrow are affected. ( J Am Acad Dermatol 2015;73:897-908.) Key words: bat; dog; gerbil; kala-azar; leishmaniasis; parasitic disorders; protozoan diseases; rodents; sandfly; tropical diseases; ulcer.

INTRODUCTION Leishmaniasis is a widespread parasitic disease that is seen predominantly in children and young adults, although it may occur at any age. Because of the enhanced opportunity for exposure and possibly not having a full developed immune system, children may be more susceptible to infection than adults.1 Children are most vulnerable to being bitten by the sandfly, which transmits the Leishmania parasite, From Dermatology,a Infectious Diseases,b Medicine,c and Preventive Medicine and Community Health,d Rutgers New Jersey Medical School; Dermatology,e Taiz University School of Medicine, Yemen; and the Rutgers School of Public Affairs and Administration, Newark.f Funding sources: None. Conflicts of interest: None declared. Accepted for publication August 22, 2014. Reprint requests: Robert A. Schwartz, MD, MPH, FRCP (Edin), Professor and Head, Dermatology, Rutgers University New Jersey Medical

Abbreviations used: LRV: PKDL: WHO:

Leishmania RNA virus postekala-azar dermal leishmaniasis World Health Organization

while indoors asleep or while outdoors.2-4 This disorder can affect both visceral organs and cutaneous surfaces (Table I). In its more common School, 185 S Orange Ave, Newark, NJ 07103-2714. E-mail: [email protected]. 0190-9622/$36.00 Ó 2014 by the American Academy of Dermatology, Inc. http://dx.doi.org/10.1016/j.jaad.2014.08.051 Date of release: December 2015 Expiration date: December 2018

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cutaneous form, it is characterized by ulcers on the face and extremities, which, even after healing, may disfigure a child and lead to social stigma.6-8 The World Health Organization (WHO) estimates that up to 1.2 million cases of cutaneous leishmaniasis occur each year in 98 countries and territories on 5 continents.9 In its visceral form, which affects up to 400,000 people worldwide each year, the mortality rate is 10%, making it the second most deadly tropical parasitic infection in the world after malaria.9,10 Unlike visceral leishmaniasis, which is concentrated in India, Bangladesh, South Sudan, Sudan, Brazil, and Ethiopia, cutaneous leishmaniasis is evenly distributed in Western Asia, the Mediterranean region, and Latin America.9,11 A recent rise in diagnoses in the United States has been noted and is attributable to international travel to and from endemic regions, whether by immigrants, refugees, tourists, or soldiers.9,12,13 Cutaneous leishmaniasis is endemic in southern Texas, and may also be so in northeastern Texas and southeastern Oklahoma, where a growing number of cases are being reported.13-16

HISTORY Key points d

d

d

The organism was first observed by Cunningham in 1885 In 1903, leishmaniasis, named for William Leishman, was described as causative agent of kala-azar In 1942, sandflies were proven to be the vector of leishmaniasis

Incan clay pottery depicting mutilations and other deformities suggests that American leishmaniasis may have been present during pre-Columbian times.17 The Leishmania organism was first observed by Cunningham18 in 1885 using tissue specimens from a ‘‘Delhi boil.’’19,20 He concluded that the responsible organism was not bacterial, which was the popular belief at that time. Borovsky, a Russian military surgeon working in Tashkent in 1898, described the organism in further detail, observing that the parasite was a protozoan.19,21 His findings were independently confirmed by Wright in 1903.20 In that same year, the causative agent of kala-azar was described by both William Leishman22 in London and Charles Donovan23 in Chennai.20 Although by 1928 induction of cutaneous leishmaniasis was observed in those bitten by sandflies of the genus Phlebotomus, it was not until 1942 when sandflies were decisively proven to be the vector for both cutaneous and visceral leishmaniasis.21,24,25 Only female phlebotomine sandflies have been found to be vectors. Vectorial

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Table I. Types of leishmaniasis Leishmaniasis syndromes

Cutaneous

Mucocutaneous

Visceral

Presentation

Onset within several weeks or months of exposure; typically progress from small papules to plaques and then to painless ulcers; regional lymphadenopathy and satellitosis may be evident In those infected in the Americas; may present years after cutaneous lesions have healed; presents as nasal congestion, bleeding, and mucosal erosions or inflammation; the mouth is less commonly affected than the nose; perforation of the nasal septum and destruction of the mouth, nose, and pharynx may occur Weeks to months after sandfly bite, those who become symptomatic may have fever, hepatosplenomegaly, weight loss, and pancytopenia; affects internal organs, typically the spleen, liver, and bone marrow

Data from Peters et al.5

competence of sandflies for different species of Leishmania is controlled by surface structural polymorphisms.26

EPIDEMIOLOGY Key points d

d

d

d

d

Leishmaniasis is endemic to all continents except Australia and Antarctica The worldwide prevalence of people infected with leishmaniasis is estimated at 12 million Its incidence in the United States is on the rise It appears to be becoming more common worldwide because of urbanization Ninety percent of new infections occur in Afghanistan, Iran, Saudi Arabia, Syria, Brazil, and Peru

Leishmaniasis is caused by protozoan parasites from more than 20 Leishmania species. This disease is endemic in every continent except Australia and Antarctica. Among the WHO’s list of ‘‘neglected’’ tropical infections, the estimated disease burden of leishmaniasis places it second in mortality and fourth in morbidity worldwide.10,27 The incidence of cutaneous leishmaniasis in the United States has

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been increasing for several reasons; Americans traveling to endemic areas and immigrants from these regions account for much of this rise.3,28,29 In addition, the recent activity of US troops in the Middle East has added to cases of leishmaniasis encountered in the United States.30 Between 2001 and 2006, there have been 1287 reported cases of US military personnel infected with leishmania during service in Iraq and Afghanistan.28 There were another 522 reported cases between 2002 and 2004 in personnel who served in southwest and central Asia.28 The manifestations of leishmaniasis are dependent upon the responsible species, which have geographic predilections. Old World leishmaniasis is endemic in Asia, Africa, the Mediterranean region, and the Middle East. The species responsible for Old World disease include Leishmania tropica, Leishmania major, Leishmania aethiopica, and Leishmania donovani.11,31,32 The cutaneous lesions caused by L tropica, which is hosted by the hyrax, a small mammal, are known by several names, including Oriental sore, Baghdad boil, and Delhi boil.33,34 L major and L aethiopica cause cutaneous lesions as well, whereas L donovani is implicated in visceral leishmaniasis, also known as kala-azar or black fever. In the Middle East, sandflies are most active between the months of April and November.35 In New World leishmaniasis, the offending parasites include Leishmania mexicana, Leishmania braziliensis, and Leishmania guyanensis. Its distribution range includes Central America, most of South America, and southern Texas.36 L mexicana, hosted by various forest rodents in Central America and the Southern Plains wood rat (Neotoma micropus) in southern Texas, may cause lesions similar to the Old World ulcers, roughly 50% of the time on the ear, referred to as a chiclero’s ulcer. It rarely disseminates into diffuse cutaneous leishmaniasis.6,37-40 In Texas, there is an increase in transmission in the fall.15 In addition to cutaneous lesions, L braziliensis complex, Leishmania panamensis, and L guyanensis can cause the mutilating destructive mucocutaneous leishmaniasis, referred to as espundia.41 Leishmania peruviana, which is part of the L braziliensis complex, causes cutaneous and mucocutaneous disease, known as uta, its vector residing 1000 to 3000 meters above sea level in the Peruvian Andes.42 According to the 1990 report by the WHO, the estimated worldwide prevalence of leishmaniasis was 12 million.31 A 2010 WHO report proclaimed that there are 350 million people in endemic areas at risk of developing leishmaniasis in 98 countries and territories worldwide.11,43 As a result of underreporting by countries, it is impossible to precisely determine the change in incidence. A 2012 WHO report

estimated the annual incidence of cutaneous leishmaniasis is 1.1 to 1.6 million cases with 90% occurring in India, Bangladesh, Sudan, South Sudan, Brazil, and Ethiopia.9 The highest case counts are in Afghanistan, Algeria, Colombia, Brazil, Iran, Syria, Ethiopia, Sudan, Costa Rica, and Peru.9,44,45 When considering disease in the New World alone, L braziliensis complex accounts for the most cases of human disease and has the widest geographic distribution in the Americas.36 The incidence in the Americas is probably higher than the reported rate, and is approximated at 100,000 new cases annually.44 There is concern in both of the Americas, East Africa, and Asia that new housing developments in areas where the parasite exists and increased contact between hosts and vectors as a result of environmental change, such as droughts, may cause an increase in leishmaniasis.13,46,47 Although the incidence appears to decline from 1990 estimates, the 2012 report cautions this to be a conservative estimate because of broad underreporting; many affected individuals do not have medical care access or have been misdiagnosed.48 Sandflies favor resting and breeding in cooler climates with thick vegetation as opposed to urban settings.46 Rapid urbanization and changes in precipitation have been linked to changes in leishmaniasis infection. Growth of metropolitan areas in Brazil has caused a reemergence of New World leishmaniasis.49 Domestic dogs are the predominant reservoir of Leishmania infantum, but removing seropositive canines has not been an adequate method of reducing incidence of leishmaniasis, because up to 20% of canines are seropositive in Brazil.49 In the past decade, eastern Jerusalem has seen a sharp increase in L tropica in both areas of poor and modern waste management. Incidence in Israel has also risen with the extension of residential neighborhoods into previously uninhabited areas.46 Dry spells have created increases in the number of cases of New World leishmaniasis during drought in Texas and periods of decreased rainfall in Colombia.13,50

ETIOLOGY Key points d

d

d

d

The genus Leishmania is divided into 2 subgenera: Leishmania and Viannia Leishmaniasis is transmitted by female sandflies Sandflies are silent and tiny, being one-third the size of a mosquito Reservoirs include man, dogs, leopards, hyenas, rodents, bats, and baboons

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Fig 1. Leishmaniasis. Life cycle. Leishmaniasis is transmitted by the bite of infected female phlebotomine sandflies. (1) The sandflies inject the infective stage (ie, promastigotes) from their proboscis during blood meals. (2) Promastigotes that reach the puncture wound are phagocytized by macrophages and other types of mononuclear phagocytic cells. (3) Progmastigotes transform in these cells into the tissue stage of the parasite (ie, amastigotes), which (4) multiply by simple division and proceed to infect other mononuclear phagocytic cells. Parasite, host, and other factors affect whether the infection becomes symptomatic and whether cutaneous or visceral leishmaniasis results. (5, 6) Sandflies become infected by ingesting infected cells during blood meals. In sandflies, amastigotes transform into promastigotes, (7) develop in the gut (in the hindgut for leishmanial organisms in the Viannia subgenus and in the midgut for organisms in the Leishmania subgenus), and (8) migrate to the proboscis. Courtesy of the Centers for Disease Control and Prevention.

Leishmaniasis is caused by parasites of the genus Leishmania. They are transmitted by female sandflies and have adapted to canines and man, as well as several other mammalian species, including rodents, bats, baboons, leopards, and hyenas.51 The life cycle of the unicellular Leishmania species begins in the gut of the phlebotomine sandfly, which belongs to the genus Phlebotomus in the Old World and Lutzomyia in the New World.36,52 The sandfly is a small insect that is silent and one-third the size of a mosquito. These insects rest during the day in cooler areas of vegetation and are active between dusk and dawn; bites may or may not be painful.53 The sandfly

has a life span of about 30 days and is actually a poor flier, going up to only approximately 2 meters, covering only short distances at a time.21 Identification of an RNA virus, Leishmania RNA virus (LRV)-1 in New World parasites, L braziliensis and L guyanensis, and LRV-2 in Old World parasite, L major, has led to the belief that development of mucocutaneous leishmaniasis is virally mediated.54-57 LRV is a member of the Totiviridae family and has a double-stranded RNA genome that encodes a RNAdependent RNA polymerase in order to undergo viral double-stranded RNA replication and single-strand RNA transcription.58 The virus may be recognized by

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Table II. Clinical disease of leishmaniasis in humans Leishmania species

New World L mexicana L braziliensis L guyanensis L amazonensis L panamensis L venezuelensis L lainsoni L garnhami L pifanoi L peruviana L colombiensis Old World L donovani L tropica L major L aethiopica L killicki Old and New World L infantum

Clinical features

Main reservoir host

Cutaneous Cutaneous and mucocutaneous Cutaneous Cutaneous Cutaneous and mucocutaneous Cutaneous Cutaneous Cutaneous Cutaneous Cutaneous Cutaneous

Forest rodents Rain forest rodents Two-toed forest sloth Rain forest rodents, marsupial, and fox Tree sloth Unknown Forest rodent Opossum Unknown Dog Sloth

Cutaneous and visceral Cutaneous Cutaneous Cutaneous Cutaneous

Dog, fox, opossum, and rat Rock hyrax Gerbils and other rodents Hyrax Unknown

Cutaneous and visceral

Dog

Data from Spickler, Galyon, and Lofstedt,33 Matayoshi et al,62 and Suster and Ronnen.63

Fig 2. Clustered nodules of leishmaniasis on cheek of a Yemeni patient.

the host Toll-like receptor 3, initiating destruction of the parasite, creating dispersal of LRV and triggering a metastatic hyperinflammatory reaction of proinflammatory cytokines and chemokines.58 Parasite life cycle Key points d This parasite is extracellular and flagellated in its promastigote form d It multiplies in the vector’s gut by binary fusion d The parasite enters its host when the female sandfly feeds d The parasite becomes intracellular and nonflagellated in its host d The cycle is completed when the sandfly feeds on an infected host

In these insect vectors, the parasites are flagellated and are found extracellularly. At this stage, the dimorphic organism is in its promastigote or leptomonad form, which multiplies in the vector’s gut via binary fission.21,59 After migrating to the salivary glands, the parasites enter the host when the female sandfly feeds, which usually occurs on exposed areas of the body.60 Once inside human, canine, or rodent hosts, the parasites are ingested by dermal macrophages, where they exist as intracellular nonflagellated organisms, beginning the other half of their life cycle as amastigotes or leishmanial forms21,59,61 (Fig 1). The cycle is completed when the sandfly feeds on an infected host, and the parasite moves to the gut where metamorphosis into the promastigote form takes place. The etiology of the various disease expressions is caused by several different organisms of the genus Leishmania (Table II). This genus is divided into 2 subgenera, Leishmania and Viannia, the former consisting of leptomonads that multiply anterior to the pylorus in the gut of the sandfly and the latter comprised of leptomonads replicating in the midand hindgut.11,31 These are further classified into the complexes; L donovani, L tropica, L major, L aethiopica, and L mexicana form the subgenus Leishmania, and L braziliensis and L guyanensis form the subgenus Viannia.11,31,64 Finally, the complexes are composed of species based on intrinsic qualities of the parasite, such as isoenzymes. The taxonomic classification for Leishmania complexes

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Fig 5. Erosion on a lip caused by Old World leishmaniasis.

Fig 3. Ulcerated plaque on the eyelid caused by Old World leishmaniasis.

Fig 6. Solitary ulcer from leishmaniasis in American tourist who traveled to Southern Africa and who also has African rickettsiosis.

Fig 4. Multiple ulcers on the legs caused by Old World leishmaniasis.

and species are frequently being revised because of the discovery of new organisms with subtle variations of known species.65

Fig 7. Slowly progressing nodules on the face at the periphery of old scars from cutaneous ulceration, from chronic relapsing cutaneous leishmaniasis (leishmania recidivans). d

d

CLINICAL MANIFESTATIONS Old World cutaneous leishmaniasis Key points d Old World cutaneous leishmaniasis may present in the following forms: localized, chronic relapsing, or diffuse

d

Acute cutaneous leishmaniasis often resembles a furuncle or Staphylococcus aureus infection Infection with Leishmania tropica typically causes \3 ulcers, the majority occurring on the head, and resolves within 2 years Leishmania major infections usually feature [3 ulcers that are self-limited and heal within 1 year

Old World cutaneous leishmaniasis has 3 different forms: localized, chronic relapsing, and diffuse.

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Fig 8. Leishmaniasis. Multiple cutaneous crusted erosive plaques in tourist who returned from a rainforest in South America, caused by Leishmania panamensis.

Fig 9. Leishmaniasis. More exudative ulcers, 1 month later, in the same untreated patient who had returned from the South American rainforest.

Fig 10. Leishmaniasis. Well demarcated leg ulcers in an American medical student who returned from a tropical medicine elective in the rainforest of Ecuador, caused by Leishmania braziliensis.

Localized cutaneous leishmaniasis has an incubation period that typically ranges from 2 to 4 weeks, but that may range from a few days to 3 years.66 It begins as an asymptomatic papule or papules, developing occasionally with nodules, at the site of the sandfly bite. The papules enlarge and form well circumscribed ulcers with a raised violaceous border caused by epidermal breakdown (Figs 2-6).67 Acute

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Fig 11. Colonoscopy in diffuse cutaneous leishmaniasis in a patient with AIDS from Central America.

cutaneous leishmaniasis often is mistaken for furuncles, furuncular myiasis, or Staphylococcus aureus infection.68,69 When a lesion heals, it forms a depressed scar. L tropica infection results in few lesions; 63% of affected individuals have 1 lesion and 95% have\3 lesions.70 Sixty percent to 76% occur on the head or neck, with 30% to 36% noted on the extremities and the rest on the trunk.1 The lesions are usually self-limited, with 73% spontaneously healing within 2 years.70 In contrast to L tropica, L major typically results in multiple ulcers ranging in number from 1 to 20.71 However, it is also a self-limited disease, with healing usually occurring within a year.4 Cutaneous leishmaniasis caused by L aethiopica gives rise to slower-growing ulcers than the other Old World types. These will also take longer to heal—usually between 2 and 5 years.11 L aethiopica is the organism responsible for diffuse cutaneous leishmaniasis in the Old World, which is rare. Chronic relapsing cutaneous leishmaniasis, or leishmania recidivans, is predominantly caused by L tropica. It manifests as slowly progressing papules, usually occurring on the face at the periphery of old scars, in patients with a previous cutaneous ulceration11,31 (Fig 7). In 1 study, the mean age of onset of lesions ranged from 10 months to 8 years.4

New World cutaneous leishmaniasis Key points d Leishmania braziliensis infection often causes severe disease d A host may be infected by 2 Leishmania species simultaneously d Leishmania mexicana may induce an ear ulceration, referred to as a chiclero’s ulcer d Leishmania panamensis infection may produce a nonhealing, spreading ulceration along lymphatic channels

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Fig 12. Diffuse cutaneous leishmaniasis in a patient with AIDS from Central America.

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Fig 14. Leishmaniasis embedded in squamous cell carcinoma in the conjunctiva of a patient with HIV.

spread along the lymphatics, resembling sporotrichosis. This condition, known regionally as ‘‘pianbois,’’ requires treatment for cure and frequently recurs.11,31

Fig 13. Cutaneous nodules on hand in diffuse cutaneous leishmaniasis in a patient with AIDS from Central America.

New World cutaneous leishmaniasis also has several clinical forms (Figs 8-10). Chiclero’s ulcer, caused by L mexicana, originally seen in gum (chicle) collectors, consists of a slowly evolving ulcer occurring on the face or pinna of the ear. It takes no more than 6 months to develop and may persist for 20 years.11,31 Uta is a form predominantly seen in preschool age children in Peru. It is caused by L peruviana and manifests as a few self-healing cutaneous lesions that involve the mucosa only by contiguous spread.6 Although rare, 2 different species of Leishmania may coinfect the same reservoir. For example, a patient in Peru with cutaneous leishmaniasis may have simultaneous infections of L braziliensis and Leishmania lainsoni.72 Simultaneous infection of L tropica and Rickettsia typhi and Rickettsia rickettsii may also occur.73 L panamensis gives rise to ‘‘ulcera de Bejuco,’’ which is characterized by shallow ulcers that frequently metastasize along lymphatic channels. These lesions do not heal spontaneously and may cause nasopharyngeal mucosal destruction in 2% to 5% of cases.6 L braziliensis infection results in severe cutaneous disease that is more frequently associated with satellite papules, subcutaneous nodules, and lymph node involvement than the other types of Leishmania.4 It usually requires treatment to eradicate. L guyanensis causes multiple ulcers that may

Diffuse cutaneous leishmaniasis Key points d Diffuse cutaneous leishmaniasis is comprised of painless nodules that may affect most of the skin on the body d Thirty percent of patients with diffuse cutaneous leishmaniasis will have oral or nasopharyngeal involvement d The causative species are Leishmania aethiopica in the Old World and Leishmania mexicana in the New World d Colonic infiltration has been observed in patients with immune reconstitution inflammatory syndrome Diffuse cutaneous leishmaniasis was first described in 1913 by Thomson and Balfour74 in Africa. It appears as painless nodules that slowly progress and eventually affect nearly the entire cutaneous surface, although it has a predilection for the skin of the face, ears, elbows, and knees.75 In some cases, the rash may have a xanthomatous or verrucous appearance.45 Thirty percent of cases eventually develop parasitic invasion of the nasopharyngeal and oral mucosa.76 The lesions contain an abundance of parasites and give the face and ears a characteristic leonine facies that mimics lepromatous leprosy.77 Secondary infection of lesions is common.77 The offending parasites are L aethiopica in the Old World form and L mexicana in the New World.31 Therapy is required regardless of etiology, but resistance to treatment is extremely common. An altered cellular immune response prevents an appropriate TH2 type reaction, resulting in disease chronicity.76 Diffuse cutaneous leishmaniasis with large hypopigmented skin lesions may mimic tuberculoid leprosy.78 Diffuse cutaneous leishmaniasis, which may include colonic infiltration, has been described in the

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setting of immune reconstitution inflammatory syndrome after the initiation of highly active retroviral therapy79,80 (Figs 11-13). Leishmaniasis should be regarded as an immune reconstitution inflammatory syndromeelinked disease.79 Mucocutaneous leishmaniasis Key points d Mucocutaneous leishmaniasis usually occurs after resolution of cutaneous lesions d Nasal and oral cavities are preferentially affected d Mucocutaneous leishmaniasis rates range from 3% to 20% in endemic areas Mucocutaneous leishmaniasis usually occurs after the apparent resolution of cutaneous infection, although it can coexist with skin involvement.81 Lesions normally appear within 2 years of cutaneous infection, but may take as many as 30 years.82 The route of infection spread may be either hematogenous or lymphatic.77 L braziliensis accounts for most cases of mucocutaneous leishmaniasis, but L panamensis, L guyanensis, and Leishmania amazonensis have also been implicated.60 The nasal and oral cavities are preferentially affected; ulcerative lesions may extend into the oropharynx and the trachea.77 Cartilage and vocal cords are susceptible to the parasite; bony structures are spared.77 Mucocutaneous disease can be markedly disfiguring and even life-threatening; treatment is essential to control the disease. In endemic countries, the percentage of cases of cutaneous leishmaniasis with subsequent mucosal involvement is about 3% to 5%, but may be as high as 20% or more in certain regions.83 It is unknown why some are more susceptible to mucocutaneous leishmaniasis while others develop only the cutaneous form. Men may be more susceptible.11,83 Visceral leishmaniasis Key points d Visceral leishmaniasis is also known as kalaazar d Visceral leishmaniasis often affects the liver, spleen, and bone marrow d Visceral leishmaniasis is caused by Leishmania donovani, Leishmania infantum, or Leishmania chagasi d Cutaneous leishmaniasis in those with resolved visceral leishmaniasis is referred to as postekala-azar dermal leishmaniasis Visceral leishmaniasis, or kala-azar, affects the liver, spleen, bone marrow, and other viscera. An associated cutaneous disease may occur, referred to

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as postekala-azar dermal leishmaniasis (PKDL). The presentation is dependent upon the species causing the infection. In East Africa, approximately 2% of patients with visceral leishmaniasis develop PKDL. A papular rash appears on the face and upper extremities during, or several months after, treatment of visceral disease.84 This form is not disfiguring and tends to resolve without any additional therapy. The epidemiologic and clinical manifestations are different in India, where Bramachari85 first described the disease.8 In India, 20% of patients with visceral leishmaniasis develop cutaneous disease years after the visceral involvement resolves.86 PKDL is first evident with depigmented, nonulcerating macules or plaques on the face, neck, trunk, and extremities, and is usually followed by nodules on similar areas of the body.84,86 Because of an overlapping geographic location and clinical appearance, PKDL is often confused with leprosy. PKDL rarely occurs in China and South America; to our knowledge, it has not been described in the Mediterranean area.84,86 Visceral leishmaniasis is usually caused by the L donovani complex, which includes L donovani, L infantum, and L chagasi.87 Visceral leishmaniasis has also been reported with infection from L tropica.88 The L donovani complex may coexist with HIV infection where leishmaniasis is endemic or in HIV patients who have traveled to these areas.89 Multiple patients with HIV have developed visceral leishmaniasis, including cases of Leishmania within Kaposi sarcoma lesions.90-92 Leishmania may exist within cutaneous cancers, including both basal cell and squamous cell carcinomas62,63 (Fig 14). Because the parasite may be found in unaffected skin, its presence in a biopsy specimen may be simply an incidental finding.5,91,92 REFERENCES 1. Solomon M, Schwartz E, Pavlotsky F, Sakka N, Barzilai A, Greenberger S. Leishmania tropica in children: a retrospective study. J Am Acad Dermatol. 2014;71:271-277. 2. Goldman L. Types of American cutaneous leishmaniasis— dermatological aspects: a review. Am J Trop Med Hyg. 1947; 27:561-584. 3. Kim YA, Schwartz RA. The influence of migration and travel. United States of America Global Dermatology Diagnosis and management according to geography, climate, and culture. Berlin, Germany: Springer-Verlag; 1994. pp. 45-50. 4. Melby PC, Kreutzer RD, McMahon-Pratt D, Gam AA, Neva FA. Cutaneous leishmaniasis: review of 59 cases seen at the National Institutes of Health. Clin Infect Dis. 1992;15:924-937. 5. Peters BS, Fish D, Golden R, Evans DA, Bryceson AD, Pinching AJ. Visceral leishmaniasis in HIV infection and AIDS: clinical features and response to therapy. Q J Med. 1990;77:1101-1111. 6. Koff AB, Rosen T. Treatment of cutaneous leishmaniasis. J Am Acad Dermatol. 1994;31:693-708.

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Cutaneous and mucocutaneous leishmaniasis: Clinical perspectives.

Leishmaniasis is endemic in 98 countries and territories, with 1.2 million new cases per year, making it a worldwide concern. The deadly visceral form...
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