What Caused This Crusted Plaque?

Patient presentation

A 5-year-old otherwise healthy girl had a 6-month history of developing a non-healing crusted plaque on the dorsum of the nose. The plaque started as a pruritic red papule, which slowly enlarged into an ulcerated lesion. The ulcer was subsequently covered with a thick superficial crust and failed to heal despite several courses of systemic antibiotics. No associated systemic symptoms were reported. Clinical examination revealed a 2 cm x 3 cm, indurated, crusted plaque surrounded by a pink hue present on the dorsum of the nose. There was no regional or generalized lymphadenopathy and no mucosal changes were noted. A review of her systems was unremarkable. Microscopic examination of a smear from the border of the lesion using H & E and Giemsa stains revealed histiocytes filled with microorganisms with identifiable kinetoplasts.

What is Your Diagnosis?

Diagnosis: Cutaneous Leishmaniasis

The first descriptions of cutaneous leishmaniasis (CL) can be traced back to the ninth century (Balkh sore). However, the Leishmania protozoan was first described in 1903 by Leishman and Donovan, working separately.¹ Leishmaniases represent a spectrum of several vector-borne parasitic diseases of variable severity, ranging from self-healing cutaneous papular or ulcerated lesions, to life-threatening visceral disease, each caused by one of the species of genus Leishmania. The parasite is transmitted by female sandflies (Phlebotomus in the Old World countries and Lutzomyia in those of the New World). Leishmaniases are classified into three forms: cutaneous (oriental sore), mucocutaneous (espundia) and visceral (kala azar). Leishmaniasis is endemic in 88 countries throughout Asia, Africa, Europe and North and South America. The population at risk is more than 350 million.² The World Health Organization estimates that at least 1.5 million cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis occur each year. Individuals at high risk of CL include military personnel and those who travel to or live in areas of the tropics, subtropics and southern Europe where the disease is endemic.³ Approximately 90% of all cases of CL occur in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria.² The cutaneous form of leishmaniasis, the most common type, represents 50% to 75% of all new cases. The incidence of leishmaniasis is greater in the Old World than in the New World. Old World disease is caused by several Leishmania species, including L. major, L. tropica, and L. infantum. It is found in widely scattered parts of Asia, Africa and Europe, and in much of the Middle East, especially in the Jordan Valley, Sinai Peninsula, Iran, Iraq, and eastern Saudi Arabia. New World CL, also known as chiclero ulcer, uta, pian bois and bay sore, is caused by different Leishmania species, including L. mexicana, L. braziliensis, L. amazonensis and L. chagasi. It is found as far north as Texas and as far south as Brazil, including Mexico and Central America.⁴

Clinical Features of CL

Following the bite from an infected sandfly, the disease may remain sub- clinical or become apparent after an incubation period of 1 week to 12 weeks.⁵ CL usually affects unclothed parts of the body easily bitten by the sandfly vector, including the face, neck and arms. CL usually begins as an erythematous, non-tender, non-pruritic papule at the site of the bite. The papule increases in size and becomes a nodule, which eventually ulcerates or becomes dry with a crusted scab. Some lesions do not ulcerate, but remain as nodules or plaques. Most patients have one or two lesions, usually on exposed sites, varying in size from 0.5 cm to 3 cm in diameter.⁶ New World CL commonly presents with a solitary primary lesion, whereas multiple primary lesions are often found in Old World disease.7 These lesions are typically asymptomatic unless complicated by secondary bacterial or fungal infections. The border is usually erythematous, raised and distinct, commonly referred to as the “volcano sign.” Multiple lesions may be present, especially if the patient encountered a nest of sandflies. Between 1 month and 36 months, depending upon both the immune status of the patient and the virulence of the infecting organism, the ulcer spontaneously regresses, leaving a scar with hypo- or hyper-pigmentation. The disease progression of New World CL is similar to that of Old World CL. Several unusual and difficult-to-diagnose clinical variants have been described. These include paronychial, chancriform, annular, palmoplantar, zosteriform and erysipeloid forms.⁸ Chiclero ulcers characteristically involve the pinna of the ears in Mexico and Central America. The infection usually remains localized without any systemic symptoms, but local lymphatic spread may occur, presenting with palpable cords and subcutaneous nodules. The immune response of the host, the virulence of the infecting species and the parasite burden determine the extent and presentation of CL. In the immunosuppressed patient, the disease can become disseminated. The species-specific immunity develops after an adequate immunologic response eliminates the infecting parasite, but resulting immunity has not been shown to be absolute; thus, reinfection can occur.

Diagnosis and Differential Diagnosis

In endemic areas, the diagnosis of CL can be established on clinical grounds.¹¹ A skin scraping for touch preparation using Wright-Giemsa stain or a biopsy from the lesion edge may reveal the Leishmania amastigotes in macrophages or extracellular areas. The Giemsa stain is a mixture of glycerin, methanol, methylene azure and eosin used to stain blood cells producing tissues, and certain species of spirochetes and protozoans. Leishmania amastigotes can be differentiated from Histoplasma capsulatum by the presence of kinetoplasts. In early lesions histology may also reveal a macrophagic infiltrate with a slight tendency to epithelioid formation. In the later stages a tuberculoid-type granuloma with prominent lymphoid infiltration may be seen. The parasite can also be grown using one of several culture media and speciated through isoenzyme analysis or monoclonal antibody. Serology for CL is not helpful because of variable antibody elevation.¹² In the differential diagnosis, consider infective granulomas such as lupus vulgaris, deep fungal infections, syphilis, neoplasms, sarcoidosis, tuberculosis and leprosy. In children, impetigo and prurigo may be mistaken for CL.

Treatment and Prevention

Treatment of CL is often difficult. Even though most cutaneous lesions will heal spontaneously, their duration cannot be predicted in an individual case. In general, New World CL tends to be more severe and longer lasting than Old World CL, which often is self-limiting. Lesions caused by L. major usually heal after about 18 weeks, while lesions caused by L. tropica may last for several years. In general, only large, multiple or diffuse lesions of the face, head and neck need to be considered for therapeutic intervention. Local care, including treatment of secondary bacterial infection, is also essential for wound healing. Pentavalent antimonials (sodium stibogluconate and meglumine antimoniate) remain the mainstay of systemic therapy despite the toxicity associated with their use.¹³ They are administered intralesionally or parenterally (IM or IV). The most commonly used antimonial agent in the United States is sodium stibogluconate (Pentostam). A dose of 20mg/kg/day for 20 days cures more than 90% of cases in a single course.¹⁴ Side effects associated with systemic antimonials include myalgias, arthralgias, abdominal symptoms, liver enzyme elevation, pancreatitis, bone marrow suppression, neuropathy, cardiac toxicity and sudden death.¹⁴ Pentamidine (Pentam 300) is considered to be less toxic. It has been found effective in treating New World CL, but its efficacy to treat the Old World disease remains to be determined. Alternatives are parenteral antifungal agents (amphotericin B), oral azoles (fluconazole, itraconazole and ketoconazole), allopurinol, cryotherapy, local excision of a small focus, and topical paromomycin. New and promising agents include imiquimod (Aldara)¹⁵ and miltefosine.¹⁶ No FDA-approved vaccine or prophylactic medication to prevent leishmaniasis is available.¹ Personal protective measures to decrease risk for infection include avoiding areas where leishmaniasis is endemic, particularly from dusk through dawn. Use of permethrin-treated bed nets and clothing is recommended to minimize the amount of exposed skin. Also, the application of repellents containing 30% to 35% DEET to exposed skin is advised. With increasing incidence of travel during the last two decades, much attention has been focused on leishmaniasis, which may lead to better therapeutic agents for treatment, and potential vaccines to prevent the infection.

Call for Cases If you have a case you’d like to see published, send a write-up (1,200 to 1,500 words) and an image of the patient’s condition to: Dr. Amor Khachemoune, SUNY Downstate Medical Center Department of Dermatology Box 46 450 Clarkson Avenue Brooklyn, NY 11203 Or, e-mail them to amorkh@pol.net.

Patient presentation

A 5-year-old otherwise healthy girl had a 6-month history of developing a non-healing crusted plaque on the dorsum of the nose. The plaque started as a pruritic red papule, which slowly enlarged into an ulcerated lesion. The ulcer was subsequently covered with a thick superficial crust and failed to heal despite several courses of systemic antibiotics. No associated systemic symptoms were reported. Clinical examination revealed a 2 cm x 3 cm, indurated, crusted plaque surrounded by a pink hue present on the dorsum of the nose. There was no regional or generalized lymphadenopathy and no mucosal changes were noted. A review of her systems was unremarkable. Microscopic examination of a smear from the border of the lesion using H & E and Giemsa stains revealed histiocytes filled with microorganisms with identifiable kinetoplasts.

What is Your Diagnosis?

Diagnosis: Cutaneous Leishmaniasis

The first descriptions of cutaneous leishmaniasis (CL) can be traced back to the ninth century (Balkh sore). However, the Leishmania protozoan was first described in 1903 by Leishman and Donovan, working separately.¹ Leishmaniases represent a spectrum of several vector-borne parasitic diseases of variable severity, ranging from self-healing cutaneous papular or ulcerated lesions, to life-threatening visceral disease, each caused by one of the species of genus Leishmania. The parasite is transmitted by female sandflies (Phlebotomus in the Old World countries and Lutzomyia in those of the New World). Leishmaniases are classified into three forms: cutaneous (oriental sore), mucocutaneous (espundia) and visceral (kala azar). Leishmaniasis is endemic in 88 countries throughout Asia, Africa, Europe and North and South America. The population at risk is more than 350 million.² The World Health Organization estimates that at least 1.5 million cases of cutaneous leishmaniasis and 500,000 cases of visceral leishmaniasis occur each year. Individuals at high risk of CL include military personnel and those who travel to or live in areas of the tropics, subtropics and southern Europe where the disease is endemic.³ Approximately 90% of all cases of CL occur in Afghanistan, Brazil, Iran, Peru, Saudi Arabia and Syria.² The cutaneous form of leishmaniasis, the most common type, represents 50% to 75% of all new cases. The incidence of leishmaniasis is greater in the Old World than in the New World. Old World disease is caused by several Leishmania species, including L. major, L. tropica, and L. infantum. It is found in widely scattered parts of Asia, Africa and Europe, and in much of the Middle East, especially in the Jordan Valley, Sinai Peninsula, Iran, Iraq, and eastern Saudi Arabia. New World CL, also known as chiclero ulcer, uta, pian bois and bay sore, is caused by different Leishmania species, including L. mexicana, L. braziliensis, L. amazonensis and L. chagasi. It is found as far north as Texas and as far south as Brazil, including Mexico and Central America.⁴

Clinical Features of CL

Following the bite from an infected sandfly, the disease may remain sub- clinical or become apparent after an incubation period of 1 week to 12 weeks.⁵ CL usually affects unclothed parts of the body easily bitten by the sandfly vector, including the face, neck and arms. CL usually begins as an erythematous, non-tender, non-pruritic papule at the site of the bite. The papule increases in size and becomes a nodule, which eventually ulcerates or becomes dry with a crusted scab. Some lesions do not ulcerate, but remain as nodules or plaques. Most patients have one or two lesions, usually on exposed sites, varying in size from 0.5 cm to 3 cm in diameter.⁶ New World CL commonly presents with a solitary primary lesion, whereas multiple primary lesions are often found in Old World disease.7 These lesions are typically asymptomatic unless complicated by secondary bacterial or fungal infections. The border is usually erythematous, raised and distinct, commonly referred to as the “volcano sign.” Multiple lesions may be present, especially if the patient encountered a nest of sandflies. Between 1 month and 36 months, depending upon both the immune status of the patient and the virulence of the infecting organism, the ulcer spontaneously regresses, leaving a scar with hypo- or hyper-pigmentation. The disease progression of New World CL is similar to that of Old World CL. Several unusual and difficult-to-diagnose clinical variants have been described. These include paronychial, chancriform, annular, palmoplantar, zosteriform and erysipeloid forms.⁸ Chiclero ulcers characteristically involve the pinna of the ears in Mexico and Central America. The infection usually remains localized without any systemic symptoms, but local lymphatic spread may occur, presenting with palpable cords and subcutaneous nodules. The immune response of the host, the virulence of the infecting species and the parasite burden determine the extent and presentation of CL. In the immunosuppressed patient, the disease can become disseminated. The species-specific immunity develops after an adequate immunologic response eliminates the infecting parasite, but resulting immunity has not been shown to be absolute; thus, reinfection can occur.

Diagnosis and Differential Diagnosis

In endemic areas, the diagnosis of CL can be established on clinical grounds.¹¹ A skin scraping for touch preparation using Wright-Giemsa stain or a biopsy from the lesion edge may reveal the Leishmania amastigotes in macrophages or extracellular areas. The Giemsa stain is a mixture of glycerin, methanol, methylene azure and eosin used to stain blood cells producing tissues, and certain species of spirochetes and protozoans. Leishmania amastigotes can be differentiated from Histoplasma capsulatum by the presence of kinetoplasts. In early lesions histology may also reveal a macrophagic infiltrate with a slight tendency to epithelioid formation. In the later stages a tuberculoid-type granuloma with prominent lymphoid infiltration may be seen. The parasite can also be grown using one of several culture media and speciated through isoenzyme analysis or monoclonal antibody. Serology for CL is not helpful because of variable antibody elevation.¹² In the differential diagnosis, consider infective granulomas such as lupus vulgaris, deep fungal infections, syphilis, neoplasms, sarcoidosis, tuberculosis and leprosy. In children, impetigo and prurigo may be mistaken for CL.

Treatment and Prevention

Treatment of CL is often difficult. Even though most cutaneous lesions will heal spontaneously, their duration cannot be predicted in an individual case. In general, New World CL tends to be more severe and longer lasting than Old World CL, which often is self-limiting. Lesions caused by L. major usually heal after about 18 weeks, while lesions caused by L. tropica may last for several years. In general, only large, multiple or diffuse lesions of the face, head and neck need to be considered for therapeutic intervention. Local care, including treatment of secondary bacterial infection, is also essential for wound healing. Pentavalent antimonials (sodium stibogluconate and meglumine antimoniate) remain the mainstay of systemic therapy despite the toxicity associated with their use.¹³ They are administered intralesionally or parenterally (IM or IV). The most commonly used antimonial agent in the United States is sodium stibogluconate (Pentostam). A dose of 20mg/kg/day for 20 days cures more than 90% of cases in a single course.¹⁴ Side effects associated with systemic antimonials include myalgias, arthralgias, abdominal symptoms, liver enzyme elevation, pancreatitis, bone marrow suppression, neuropathy, cardiac toxicity and sudden death.¹⁴ Pentamidine (Pentam 300) is considered to be less toxic. It has been found effective in treating New World CL, but its efficacy to treat the Old World disease remains to be determined. Alternatives are parenteral antifungal agents (amphotericin B), oral azoles (fluconazole, itraconazole and ketoconazole), allopurinol, cryotherapy, local excision of a small focus, and topical paromomycin. New and promising agents include imiquimod (Aldara)¹⁵ and miltefosine.¹⁶ No FDA-approved vaccine or prophylactic medication to prevent leishmaniasis is available.¹ Personal protective measures to decrease risk for infection include avoiding areas where leishmaniasis is endemic, particularly from dusk through dawn. Use of permethrin-treated bed nets and clothing is recommended to minimize the amount of exposed skin. Also, the application of repellents containing 30% to 35% DEET to exposed skin is advised. With increasing incidence of travel during the last two decades, much attention has been focused on leishmaniasis, which may lead to better therapeutic agents for treatment, and potential vaccines to prevent the infection.

Call for Cases If you have a case you’d like to see published, send a write-up (1,200 to 1,500 words) and an image of the patient’s condition to: Dr. Amor Khachemoune, SUNY Downstate Medical Center Department of Dermatology Box 46 450 Clarkson Avenue Brooklyn, NY 11203 Or, e-mail them to amorkh@pol.net.