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Skin rash for 15 years
CASE REPORT
Case report
Skin rash for 15 years Sven Montelius, Kerima Maasho, Francine Pratlong, Marianne Lebbad, Lisbeth Gregory, Hannah Akuffo A 58-year-old coach driver from the central part of Sweden was generally in good health and took no regular medication, but more than 15 years ago he first noticed multiple, blue/red, slightly raised, non-itching and nonulcerated skin changes on his lower abdomen, back, buttocks, and groin. Several years later similar skin changes appeared on his face, around his nostrils and on his earlobes (figure). He had noted nocturnal sweats but no fever. Extensive investigations by specialists undertaken over the years led to no definitive diagnosis. Findings included lymphohistiocytic granulomas in dermal biopsy samples and slight hepatosplenomegaly by ultrasonography. The spleen measured 16 cm. Histological examination of bone marrow and liver biopsy specimens showed no remarkable features. Tests for syphilis, Borrelia sp, and mycobacteria were negative. In 1996, skin smears to detect leprosy were negative. When he was referred to the Swedish Institute for Infectious Disease Control in October, 1996, his titre of antibodies to leishmania was found to be high (1/270). New skin biopsy samples and imprints revealed intracellular amastigote of leishmania by giemsa staining. Tuberculin test (2 TU PPD) and HIV-1 antibody test were negative. White blood cell counts were low (3·2–4·8⫻109/L). Haemoglobin and platelet counts were within normal ranges. He had made several week-long trips with tourist coaches to Italy, France, Greece, and Spain from 1975 to 1985. He has never travelled outside Europe. The geographical exposure and discrete signs of visceral involvement suggested the probable cause was Leishmania infantum. The parasites from the cultures grew extremely slowly. Starch gel electrophoresis of 15 isoenzyme complexes1 identified a zymodeme of L infantum, not previously described, MON-253. This differed by one enzyme from the MON-1 zymodeme (G6PD95 instead of GP6D100). In-vitro analysis of cultured mononuclear cells before and after treatment showed low PPD-induced interferon-␥. Cells proliferated normally to the non-specific T-cell mitogen, phytohaemagglutinin. Liposomal amphotericin B (AmBisome) was given intravenously over 14 days (total 25·5 mg per kg bodyweight, total 2780 mg2). 10 months after treatment, his skin changes had healed and no further nocturnal sweats had been noted. His white blood cell count did not change. Ultrasonography showed a slight decrease in the size of his spleen. Antigen and mitogen-induced interferon-␥ concentrations were enhanced
Facial lesions The patient gave his permission for this photograph to be published.
after treatment. Both natural-killer and CD4 T cells contributed to proliferation and interferon-␥ production. Strangely, the patient noted that before treatment he did not have any local reaction to mosquito bites. However, after treatment he developed strong local reaction to such bites. He was well when last seen in July, 1998. Leishmania sp enter and multiply in the monocytemacrophages of the skin, viscera, or mucocutaneous tissues. Control of multiplication involves activation and proliferation of interferon-␥-producing CD4 cells.3 L infantum, a species that mainly infects dogs in Europe, causes a visceral infection in children but can cause atypical cutaneous leishmaniasis.4 What makes a Leishmania sp able to persist in an immunocompetent host for many years, without being eliminated or spreading extensively? Is it an unusual characteristic of the host or of the infecting parasite? Liposomal amphotericin B was an effective treatment. While visceral leishmaniasis was not an overt feature in this patient, the slight reduction in spleen size after treatment suggests that the disease was spreading. There was nothing to support a generalised T-cell immunosuppression, which is a feature of late-stage visceral leishmaniasis, but enhanced interferon-␥ secretion after treatment suggests some immunosuppression before treatment. It appears that atypical slow-growing cutaneous leishmaniasis may occur in immunocompetent individuals in Europe. It could mean that there are many forms of L infantum that induce diverse forms of disease and this newly described zymodeme may be rare or the diseases it causes may be unrecognised. The infection appears amenable to treatment but would probably have more serious consequences if untreated. We thank Jean-Pierre Dedet for his help with the isoenzyme determination. Funds from the Swedish Medical Research Council (MFR) and the Swedish International Development Agency (Sida/SAREC) supported this study.
References 1
Lancet 1998; 352: 1438 Department of Infectious Diseases, Mälarsjukhuset Eskilstuna, Sweden (S Montelius MD); Microbiology and Tumour Biology Centre and Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden (K Maasho MSc, M Lebbad, L Gregory MSc, H Akuffo PhD); and Laboratoire d’Ecologie Medicale et Pathologie parasitaire, Montpellier, France (F Pratlong PhD) Correspondence to: Dr Hannah Akuffo, MTC, Karolinska Institute, Box 280, 17177 Stockholm, Sweden
1438
2 3
4
Rioux JA, Lanotte G, Serres E, Pratlong F, Bastien P, Périère J. Taxonomy of leishmania: use of isoenzymes—suggestions for a new classification. Ann Parasit Hum Comp 1990; 65: 111–25. Gradoni L, Bryceson A, Desjeux P. Treatment of Mediterranean visceral leishmaniasis. Bull World Health Organ 1995; 73: 191–97. Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM. Reciprocal expression of interferon ␥ or interleukin 4 during the resolution or progression of murine leishmaniasis: evidence for expansion of distinct helper T cell subsets. J Exp Med 1989; 169: 59–72. Jimenez M, Ferrer-Dufol M, Canavate C, et al. Variability of Leishmania (Leishmania) infantum among stocks from immunocompromised, immunocompetent patients and dogs in Spain. FEMS Microb Let 1995; 131: 197–204.
THE LANCET • Vol 352 • October 31, 1998
Case report
Skin rash for 15 years Sven Montelius, Kerima Maasho, Francine Pratlong, Marianne Lebbad, Lisbeth Gregory, Hannah Akuffo A 58-year-old coach driver from the central part of Sweden was generally in good health and took no regular medication, but more than 15 years ago he first noticed multiple, blue/red, slightly raised, non-itching and nonulcerated skin changes on his lower abdomen, back, buttocks, and groin. Several years later similar skin changes appeared on his face, around his nostrils and on his earlobes (figure). He had noted nocturnal sweats but no fever. Extensive investigations by specialists undertaken over the years led to no definitive diagnosis. Findings included lymphohistiocytic granulomas in dermal biopsy samples and slight hepatosplenomegaly by ultrasonography. The spleen measured 16 cm. Histological examination of bone marrow and liver biopsy specimens showed no remarkable features. Tests for syphilis, Borrelia sp, and mycobacteria were negative. In 1996, skin smears to detect leprosy were negative. When he was referred to the Swedish Institute for Infectious Disease Control in October, 1996, his titre of antibodies to leishmania was found to be high (1/270). New skin biopsy samples and imprints revealed intracellular amastigote of leishmania by giemsa staining. Tuberculin test (2 TU PPD) and HIV-1 antibody test were negative. White blood cell counts were low (3·2–4·8⫻109/L). Haemoglobin and platelet counts were within normal ranges. He had made several week-long trips with tourist coaches to Italy, France, Greece, and Spain from 1975 to 1985. He has never travelled outside Europe. The geographical exposure and discrete signs of visceral involvement suggested the probable cause was Leishmania infantum. The parasites from the cultures grew extremely slowly. Starch gel electrophoresis of 15 isoenzyme complexes1 identified a zymodeme of L infantum, not previously described, MON-253. This differed by one enzyme from the MON-1 zymodeme (G6PD95 instead of GP6D100). In-vitro analysis of cultured mononuclear cells before and after treatment showed low PPD-induced interferon-␥. Cells proliferated normally to the non-specific T-cell mitogen, phytohaemagglutinin. Liposomal amphotericin B (AmBisome) was given intravenously over 14 days (total 25·5 mg per kg bodyweight, total 2780 mg2). 10 months after treatment, his skin changes had healed and no further nocturnal sweats had been noted. His white blood cell count did not change. Ultrasonography showed a slight decrease in the size of his spleen. Antigen and mitogen-induced interferon-␥ concentrations were enhanced
Facial lesions The patient gave his permission for this photograph to be published.
after treatment. Both natural-killer and CD4 T cells contributed to proliferation and interferon-␥ production. Strangely, the patient noted that before treatment he did not have any local reaction to mosquito bites. However, after treatment he developed strong local reaction to such bites. He was well when last seen in July, 1998. Leishmania sp enter and multiply in the monocytemacrophages of the skin, viscera, or mucocutaneous tissues. Control of multiplication involves activation and proliferation of interferon-␥-producing CD4 cells.3 L infantum, a species that mainly infects dogs in Europe, causes a visceral infection in children but can cause atypical cutaneous leishmaniasis.4 What makes a Leishmania sp able to persist in an immunocompetent host for many years, without being eliminated or spreading extensively? Is it an unusual characteristic of the host or of the infecting parasite? Liposomal amphotericin B was an effective treatment. While visceral leishmaniasis was not an overt feature in this patient, the slight reduction in spleen size after treatment suggests that the disease was spreading. There was nothing to support a generalised T-cell immunosuppression, which is a feature of late-stage visceral leishmaniasis, but enhanced interferon-␥ secretion after treatment suggests some immunosuppression before treatment. It appears that atypical slow-growing cutaneous leishmaniasis may occur in immunocompetent individuals in Europe. It could mean that there are many forms of L infantum that induce diverse forms of disease and this newly described zymodeme may be rare or the diseases it causes may be unrecognised. The infection appears amenable to treatment but would probably have more serious consequences if untreated. We thank Jean-Pierre Dedet for his help with the isoenzyme determination. Funds from the Swedish Medical Research Council (MFR) and the Swedish International Development Agency (Sida/SAREC) supported this study.
References 1
Lancet 1998; 352: 1438 Department of Infectious Diseases, Mälarsjukhuset Eskilstuna, Sweden (S Montelius MD); Microbiology and Tumour Biology Centre and Swedish Institute for Infectious Disease Control, Karolinska Institute, Stockholm, Sweden (K Maasho MSc, M Lebbad, L Gregory MSc, H Akuffo PhD); and Laboratoire d’Ecologie Medicale et Pathologie parasitaire, Montpellier, France (F Pratlong PhD) Correspondence to: Dr Hannah Akuffo, MTC, Karolinska Institute, Box 280, 17177 Stockholm, Sweden
1438
2 3
4
Rioux JA, Lanotte G, Serres E, Pratlong F, Bastien P, Périère J. Taxonomy of leishmania: use of isoenzymes—suggestions for a new classification. Ann Parasit Hum Comp 1990; 65: 111–25. Gradoni L, Bryceson A, Desjeux P. Treatment of Mediterranean visceral leishmaniasis. Bull World Health Organ 1995; 73: 191–97. Heinzel FP, Sadick MD, Holaday BJ, Coffman RL, Locksley RM. Reciprocal expression of interferon ␥ or interleukin 4 during the resolution or progression of murine leishmaniasis: evidence for expansion of distinct helper T cell subsets. J Exp Med 1989; 169: 59–72. Jimenez M, Ferrer-Dufol M, Canavate C, et al. Variability of Leishmania (Leishmania) infantum among stocks from immunocompromised, immunocompetent patients and dogs in Spain. FEMS Microb Let 1995; 131: 197–204.
THE LANCET • Vol 352 • October 31, 1998