doi: 10.1111/1346-8138.12609
Journal of Dermatology 2014; 41: 926–928
CONCISE COMMUNICATION
An imported case of cutaneous leishmaniasis caused by Leishmania (Leishmania) donovani in Japan Kotaro ITO,1 Masakazu TAKAHARA,2 Makoto ITO,3 Minoru OSHIRO,4 Kenzo TAKAHASHI,5 Hiroshi UEZATO,5 Shinichi IMAFUKU1 1
Department of Dermatology, Fukuoka University Hospital, 2Department of Dermatology, Kyusyu University Hospital, Fukuoka, Department of Infection and Immunology Laboratory, Aichi Medical University, Nagakute, 4Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, and 5Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan 3
ABSTRACT Leishmaniasis is a major world health problem, and 12 million people are estimated to be infected in 88 countries. There have been few reports of leishmaniasis in Japan and all were of foreign origin; therefore diagnosis is difficult for Japanese physicians. There are 21 different pathogenic Leishmania species, and identification is obtained by polymerase chain reaction (PCR). Here we report an imported case of leishmaniasis by Leishmania (Leishmania) donovani infection from Sri Lanka. L. (L.) donovani usually causes visceral leishmaniasis, but in this case, the patient manifested cutaneous leishmaniasis. The identification of Leishmania species by PCR and investigation of the patient’s background such as nationality and disease endemicity are important for diagnosis and treatment. This is the first report of cutaneous leishmaniasis by L. (L.) donovani in Japan.
Key words:
cutaneous leishmaniasis, Leishmania (Leishmania) donovani, Sri Lanka.
INTRODUCTION Leishmaniasis is an infection caused by Leishmania protozoa and is transmitted by the bite of a sandfly.1 There are 21 different Leishmania species, and identification of the causative Leishmania species is very important, because clinical symptoms, prognosis and response to medication are different depending on the infecting Leishmania species.2 Leishmaniasis is classified into three clinical forms: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL) and visceral leishmaniasis (VL).3 Only 15 cases of CL and MCL have been reported in Japan since 1999. Here, we report a case of CL caused by Leishmania (Leishmania) donovani. Usually this species causes VL; however, CL by L. (L.) donovani has recently been prevalent in Sri Lanka.4 This is the first report of an imported CL case caused by L. (L.) donovani in Japan.
CASE REPORT A 28-year-old male Sri Lankan was admitted to our hospital in November 2013, because of a skin lesion on the left side of the lower jaw. The lesion appeared in December 2012 and was resistant to antibiotic treatment. He had been in Japan as a foreign student since April 2012 and had not traveled abroad since his arrival. His past medical and familial history was unre-
markable. The skin lesion manifested as an erythematous nodule covered with scale and crust measuring 3.0 9 2.0 cm on the left aspect of the lower jaw (Fig. 1a). Histopathological analysis demonstrated a diffuse dense infiltration of lymphocytes, plasma cells and monocytes in the dermis. Higher magnification clarified granular bodies and Leishmania amastigotes in the cytoplasm of macrophages (Fig. 2). Results of blood tests were within normal limits and did not indicate anemia or liver dysfunction. Based on these findings, we diagnosed this case as having CL. For further diagnosis, enzyme-linked immuno-sorbent assay was performed to detect IgG antibodies for the antigen of L. (L.) donovani, but was negative. To determine the causative species of Leishmania, polymerase chain reaction (PCR) was performed to amplify the heat-shock protein 70 (HSP70) gene and the cytochrome b gene from paraffin-embedded tissue specimens and frozen tissue specimens, as reported previously.5,6 Amplified DNA fragments were obtained only from frozen tissue specimens. Direct sequencing of the amplified DNA fragment identified L. (L.) donovani (Fig. 3). From these findings, we further diagnosed this case as having CL by L. (L.) donovani. The patient was treated with intraregional injections of Glucantime (8.5% meglumine antimonite) at a dose of 20 mg/kg/day administered four times. His erythematous nodule gradually disappeared and recovered as a scar after 4 weeks (Fig. 1b). He did not have general symptoms, such as fever or fatigue in the course of treatment.
Correspondence: Kotaro Ito, M.D., Department of Dermatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Fukuoka 814-0180, Japan. Email: [email protected] Received 10 June 2014; accepted 24 July 2014.
926
© 2014 Japanese Dermatological Association
Cutaneous leishmaniasis due to L. donovani
(a)
(b)
Figure 3. Amplified DNA was detected by PCR. M, size marker (100 bp ladder); N, free DNA in PCR solution; lane 1, DNA was extracted from a healthy subject; lane 2, DNA extracted from the patient skin lesion; lane 3, positive control sample with Leishmania (Viannia) braziliensis.
Figure 1. (a) Skin lesions of the left lower jaw. The erythematous nodule was 3.0 9 2.0 cm with scales and crusts. (b) After treatment with Glucantime (8.5% meglumine antimonite) administered four times. The erythematous nodule became a scar.
(a)
(b)
Figure 2. Histopathological examination of the erythematous nodule. (a) Hematoxylin and eosin staining showed diffuse infiltration of inflammatory cells including lymphocytes, plasma cells and monocytes in the dermis. (b) Higher magnification showed granular bodies and Leishmania amastigotes in the cytoplasm of macrophages (91000).
DISCUSSION Leishmaniasis is a disease caused by the parasite Leishmania protozoa transmitted by the bite of a sandfly. It is now prevalent in 88 countries and has become a major world health problem.7 It is an imported infection, because sandflies do not inhabit Japan. Leishmaniasis is clinically classified into three subtypes. VL is a systemic infection with myelopathy, hepatosplenomegaly and anemia and is fatal if not treated. MCL manifests as a destructive ulcer of the nasopharyngeal mucosa. CL shows as a nodule or papules with ulceration at the site of insect exposure. Although there have been few reports, the most common type reported in Japan is CL. The prognosis of CL is good with occasional spontaneous remission without treatment. The clinical type depends on the Leishmania species and the immune status of the host. There are 21 different pathogenic Leishmania species, and identification requires PCR. In our case, PCR analysis for the product of the HSP70 gene showed homology with L.
© 2014 Japanese Dermatological Association
(L.) donovani (100%) and L. (L.) infantum (99.92%). Moreover, in the leishmanial cytochrome b gene sequence, there was homology with L. (L.) infantum (98.9%) and L. (L.) donovani (98.78%). Usually these species cause VL, but our case manifested CL. We suspected that the patient’s original country (Sri Lanka), where he was infected, was related to the disagreement between clinical symptoms and the Leishmania species. L. (L.) donovani usually causes VL in neighboring India, Bangladesh, and Nepal, as well as in East Africa. There have been very few reports of CL caused by L. (L.) donovani in these countries. In contrast, high numbers of cases of CL caused by L. (L.) donovani have been reported in Sri Lanka with fewer reports of VL due to L. (L.) donovani. CL has not been prevalent in Sri Lanka until very recently; therefore, it is an emerging disease.8 Thus, CL caused by L. (L.) donovani appears to be a unique new infection in limited places in Sri Lanka. In leishmaniasis, a single parasite strain can cause different clinical symptoms, although the reason for this is unknown. Sujeevi et al.9 reported that 86 of 116 patients with CL in Sri Lanka were positive for L. (L.) donovani and most patients had single dry lesions on the face similar to our case. Our patient left Sri Lanka in 2012, and we speculate he had an opportunity to be infected with this new pathogen before he visited Japan. We started chemotherapy with intraregional injections of Glucantime (8.5% meglumine antimonite) because no remission was observed in the natural course for 1 year. This medication is usually employed as first choice.10 Use of Glucantime is limited to a few institutions in Japan because it is currently a non-approved orphan drug. Recently, successful treatment with liposomal amphotericin B (AmBisome) was reported for treatment of CL.11 AmBisome was approved for the treatment of leishmaniasis in June 2009 in Japan; therefore it is one of the current choices for treatment. In Japan, Glucantime or AmBisome is recommended for the treatment of CL,11 and if the condition is CL by L. (L.) donovani, we assume that this discipline works because there are few reports of VL due to L. (L.) donovani in Sri Lanka. To our knowledge, this is the first report of an imported CL caused by L. (L.) donovani in Japan. We should consider not only Leishmania species and the status of the host but also the patient’s background
927
K. Ito et al.
such as nationality and disease endemicity when diagnosing leishmaniasis.
CONFLICT OF INTEREST:
None.
REFERENCES 1 Chen LH, Wilson ME, Davis X et al. GeoSentinel Surveillance Network. Illness in long-term travelers visiting GeoSentinel clinics. Emerg Infect Dis 2009; 15: 1173–1782. 2 Uezato H, Takei K, Maruno M et al. Detection of species of the subgenus Leishmania parasites using polymerase chain reaction and southern blotting. J Dermatol 2001; 28: 475–480. 3 Masmoudi A, Hariz W, Marrekchi S, Amouri M, Turki H. Old World cutaneous leishmaniasis: diagnosis and treatment. J Dermatol Case Rep 2013; 2: 31–41. 4 Siriwardana HV, Noyes HA, Beeching NJ, Chance ML, Karunaweera ND, Bates PA. Leishmania donovani and Cutaneous Leishmaniasis, Sri Lanka. Emerg Infect Dis 2007; 13: 476–478.
928
5 Asato Y, Oshiro M, Myint CK et al. Phylogenic analysis of the genus Leishmania by cytochrome b gene sequencing. Exp.Parasitol 2009; 121: 352–361. 6 Fraga J, Montalvo AM, De Doncker S, Dujardin JC, Van der Auwera G. Phylogeny of Leishmania species based on the heat-shock protein 70 gene. Infect Genet Evol 2010:238-245.encing. Exp Parasitol 2009; 121: 352–361. 7 Desjeux P. Leishmania & HIV in Gridlok. Geneva: WHO, 1998: 1–28. 8 Sandanayaka R, Kahawita I, Gamage A, Siribaddana S, Agampodi S. Emergence of cutaneous leishmaniasis in Polonnaruwa, Sri Lanka 2008–2011. Trop Med Int Health 2014; 19: 140–145. 9 Sujeevi SK, Nawaratna SS, Weilgama DJ, Wijekoon CJ, Dissanayake M, Rajapaksha K. Cutaneous leishmaniasis, Sri Lanka. Emerg Infect Dis 2007; 13: 1068–1070. 10 Murray HW, Berman JD, Davies CR, Saravia NG. Advances in leishmaniasis. Lancet 2005; 366: 1561–1577. 11 Ono M, Takahashi K, Taira K, Uezato H, Takamura S, Izaki S. Cutaneous leishmaniasis in a Japanese returnee from West Africa successfully treated with liposomal amphotericin B. J Dermatol 2011; 38: 1062–1065.
© 2014 Japanese Dermatological Association
Journal of Dermatology 2014; 41: 926–928
CONCISE COMMUNICATION
An imported case of cutaneous leishmaniasis caused by Leishmania (Leishmania) donovani in Japan Kotaro ITO,1 Masakazu TAKAHARA,2 Makoto ITO,3 Minoru OSHIRO,4 Kenzo TAKAHASHI,5 Hiroshi UEZATO,5 Shinichi IMAFUKU1 1
Department of Dermatology, Fukuoka University Hospital, 2Department of Dermatology, Kyusyu University Hospital, Fukuoka, Department of Infection and Immunology Laboratory, Aichi Medical University, Nagakute, 4Department of Medical Biochemistry, Graduate School of Medicine, University of the Ryukyus, and 5Department of Dermatology, Graduate School of Medicine, University of the Ryukyus, Okinawa, Japan 3
ABSTRACT Leishmaniasis is a major world health problem, and 12 million people are estimated to be infected in 88 countries. There have been few reports of leishmaniasis in Japan and all were of foreign origin; therefore diagnosis is difficult for Japanese physicians. There are 21 different pathogenic Leishmania species, and identification is obtained by polymerase chain reaction (PCR). Here we report an imported case of leishmaniasis by Leishmania (Leishmania) donovani infection from Sri Lanka. L. (L.) donovani usually causes visceral leishmaniasis, but in this case, the patient manifested cutaneous leishmaniasis. The identification of Leishmania species by PCR and investigation of the patient’s background such as nationality and disease endemicity are important for diagnosis and treatment. This is the first report of cutaneous leishmaniasis by L. (L.) donovani in Japan.
Key words:
cutaneous leishmaniasis, Leishmania (Leishmania) donovani, Sri Lanka.
INTRODUCTION Leishmaniasis is an infection caused by Leishmania protozoa and is transmitted by the bite of a sandfly.1 There are 21 different Leishmania species, and identification of the causative Leishmania species is very important, because clinical symptoms, prognosis and response to medication are different depending on the infecting Leishmania species.2 Leishmaniasis is classified into three clinical forms: cutaneous leishmaniasis (CL), mucocutaneous leishmaniasis (MCL) and visceral leishmaniasis (VL).3 Only 15 cases of CL and MCL have been reported in Japan since 1999. Here, we report a case of CL caused by Leishmania (Leishmania) donovani. Usually this species causes VL; however, CL by L. (L.) donovani has recently been prevalent in Sri Lanka.4 This is the first report of an imported CL case caused by L. (L.) donovani in Japan.
CASE REPORT A 28-year-old male Sri Lankan was admitted to our hospital in November 2013, because of a skin lesion on the left side of the lower jaw. The lesion appeared in December 2012 and was resistant to antibiotic treatment. He had been in Japan as a foreign student since April 2012 and had not traveled abroad since his arrival. His past medical and familial history was unre-
markable. The skin lesion manifested as an erythematous nodule covered with scale and crust measuring 3.0 9 2.0 cm on the left aspect of the lower jaw (Fig. 1a). Histopathological analysis demonstrated a diffuse dense infiltration of lymphocytes, plasma cells and monocytes in the dermis. Higher magnification clarified granular bodies and Leishmania amastigotes in the cytoplasm of macrophages (Fig. 2). Results of blood tests were within normal limits and did not indicate anemia or liver dysfunction. Based on these findings, we diagnosed this case as having CL. For further diagnosis, enzyme-linked immuno-sorbent assay was performed to detect IgG antibodies for the antigen of L. (L.) donovani, but was negative. To determine the causative species of Leishmania, polymerase chain reaction (PCR) was performed to amplify the heat-shock protein 70 (HSP70) gene and the cytochrome b gene from paraffin-embedded tissue specimens and frozen tissue specimens, as reported previously.5,6 Amplified DNA fragments were obtained only from frozen tissue specimens. Direct sequencing of the amplified DNA fragment identified L. (L.) donovani (Fig. 3). From these findings, we further diagnosed this case as having CL by L. (L.) donovani. The patient was treated with intraregional injections of Glucantime (8.5% meglumine antimonite) at a dose of 20 mg/kg/day administered four times. His erythematous nodule gradually disappeared and recovered as a scar after 4 weeks (Fig. 1b). He did not have general symptoms, such as fever or fatigue in the course of treatment.
Correspondence: Kotaro Ito, M.D., Department of Dermatology, Faculty of Medicine, Fukuoka University, 7-45-1, Nanakuma, Fukuoka 814-0180, Japan. Email: [email protected] Received 10 June 2014; accepted 24 July 2014.
926
© 2014 Japanese Dermatological Association
Cutaneous leishmaniasis due to L. donovani
(a)
(b)
Figure 3. Amplified DNA was detected by PCR. M, size marker (100 bp ladder); N, free DNA in PCR solution; lane 1, DNA was extracted from a healthy subject; lane 2, DNA extracted from the patient skin lesion; lane 3, positive control sample with Leishmania (Viannia) braziliensis.
Figure 1. (a) Skin lesions of the left lower jaw. The erythematous nodule was 3.0 9 2.0 cm with scales and crusts. (b) After treatment with Glucantime (8.5% meglumine antimonite) administered four times. The erythematous nodule became a scar.
(a)
(b)
Figure 2. Histopathological examination of the erythematous nodule. (a) Hematoxylin and eosin staining showed diffuse infiltration of inflammatory cells including lymphocytes, plasma cells and monocytes in the dermis. (b) Higher magnification showed granular bodies and Leishmania amastigotes in the cytoplasm of macrophages (91000).
DISCUSSION Leishmaniasis is a disease caused by the parasite Leishmania protozoa transmitted by the bite of a sandfly. It is now prevalent in 88 countries and has become a major world health problem.7 It is an imported infection, because sandflies do not inhabit Japan. Leishmaniasis is clinically classified into three subtypes. VL is a systemic infection with myelopathy, hepatosplenomegaly and anemia and is fatal if not treated. MCL manifests as a destructive ulcer of the nasopharyngeal mucosa. CL shows as a nodule or papules with ulceration at the site of insect exposure. Although there have been few reports, the most common type reported in Japan is CL. The prognosis of CL is good with occasional spontaneous remission without treatment. The clinical type depends on the Leishmania species and the immune status of the host. There are 21 different pathogenic Leishmania species, and identification requires PCR. In our case, PCR analysis for the product of the HSP70 gene showed homology with L.
© 2014 Japanese Dermatological Association
(L.) donovani (100%) and L. (L.) infantum (99.92%). Moreover, in the leishmanial cytochrome b gene sequence, there was homology with L. (L.) infantum (98.9%) and L. (L.) donovani (98.78%). Usually these species cause VL, but our case manifested CL. We suspected that the patient’s original country (Sri Lanka), where he was infected, was related to the disagreement between clinical symptoms and the Leishmania species. L. (L.) donovani usually causes VL in neighboring India, Bangladesh, and Nepal, as well as in East Africa. There have been very few reports of CL caused by L. (L.) donovani in these countries. In contrast, high numbers of cases of CL caused by L. (L.) donovani have been reported in Sri Lanka with fewer reports of VL due to L. (L.) donovani. CL has not been prevalent in Sri Lanka until very recently; therefore, it is an emerging disease.8 Thus, CL caused by L. (L.) donovani appears to be a unique new infection in limited places in Sri Lanka. In leishmaniasis, a single parasite strain can cause different clinical symptoms, although the reason for this is unknown. Sujeevi et al.9 reported that 86 of 116 patients with CL in Sri Lanka were positive for L. (L.) donovani and most patients had single dry lesions on the face similar to our case. Our patient left Sri Lanka in 2012, and we speculate he had an opportunity to be infected with this new pathogen before he visited Japan. We started chemotherapy with intraregional injections of Glucantime (8.5% meglumine antimonite) because no remission was observed in the natural course for 1 year. This medication is usually employed as first choice.10 Use of Glucantime is limited to a few institutions in Japan because it is currently a non-approved orphan drug. Recently, successful treatment with liposomal amphotericin B (AmBisome) was reported for treatment of CL.11 AmBisome was approved for the treatment of leishmaniasis in June 2009 in Japan; therefore it is one of the current choices for treatment. In Japan, Glucantime or AmBisome is recommended for the treatment of CL,11 and if the condition is CL by L. (L.) donovani, we assume that this discipline works because there are few reports of VL due to L. (L.) donovani in Sri Lanka. To our knowledge, this is the first report of an imported CL caused by L. (L.) donovani in Japan. We should consider not only Leishmania species and the status of the host but also the patient’s background
927
K. Ito et al.
such as nationality and disease endemicity when diagnosing leishmaniasis.
CONFLICT OF INTEREST:
None.
REFERENCES 1 Chen LH, Wilson ME, Davis X et al. GeoSentinel Surveillance Network. Illness in long-term travelers visiting GeoSentinel clinics. Emerg Infect Dis 2009; 15: 1173–1782. 2 Uezato H, Takei K, Maruno M et al. Detection of species of the subgenus Leishmania parasites using polymerase chain reaction and southern blotting. J Dermatol 2001; 28: 475–480. 3 Masmoudi A, Hariz W, Marrekchi S, Amouri M, Turki H. Old World cutaneous leishmaniasis: diagnosis and treatment. J Dermatol Case Rep 2013; 2: 31–41. 4 Siriwardana HV, Noyes HA, Beeching NJ, Chance ML, Karunaweera ND, Bates PA. Leishmania donovani and Cutaneous Leishmaniasis, Sri Lanka. Emerg Infect Dis 2007; 13: 476–478.
928
5 Asato Y, Oshiro M, Myint CK et al. Phylogenic analysis of the genus Leishmania by cytochrome b gene sequencing. Exp.Parasitol 2009; 121: 352–361. 6 Fraga J, Montalvo AM, De Doncker S, Dujardin JC, Van der Auwera G. Phylogeny of Leishmania species based on the heat-shock protein 70 gene. Infect Genet Evol 2010:238-245.encing. Exp Parasitol 2009; 121: 352–361. 7 Desjeux P. Leishmania & HIV in Gridlok. Geneva: WHO, 1998: 1–28. 8 Sandanayaka R, Kahawita I, Gamage A, Siribaddana S, Agampodi S. Emergence of cutaneous leishmaniasis in Polonnaruwa, Sri Lanka 2008–2011. Trop Med Int Health 2014; 19: 140–145. 9 Sujeevi SK, Nawaratna SS, Weilgama DJ, Wijekoon CJ, Dissanayake M, Rajapaksha K. Cutaneous leishmaniasis, Sri Lanka. Emerg Infect Dis 2007; 13: 1068–1070. 10 Murray HW, Berman JD, Davies CR, Saravia NG. Advances in leishmaniasis. Lancet 2005; 366: 1561–1577. 11 Ono M, Takahashi K, Taira K, Uezato H, Takamura S, Izaki S. Cutaneous leishmaniasis in a Japanese returnee from West Africa successfully treated with liposomal amphotericin B. J Dermatol 2011; 38: 1062–1065.
© 2014 Japanese Dermatological Association
