Diffuse Cutaneous Leishmaniasis Acquired in Peru

Diffuse cutaneous leishmaniasis (DCL) is a rare disease that has been reported from Venezuela, the
Dominican Republic, Brazil, Mexico, Bolovia, Colombia, and Ethiopia. To our knowledge, only 1 case of
DCL has been documented from Peru; however, no specific information on the clinical presentation or
parasite species causing the disease was reported.

The disease is characterized by widely disseminated, non-ulcerative cutaneous lesions that appear as
plaques, papules or multiple nodules. The lesions do not heal spontaneously and tend to relapse afer
treatment with the currently available chemotherapeutic agents. The causative agent is usually
Leishmania Mexicana sp. In the new world and L. aethiopica in the old world. Patients with DCL have a
specific anergy to leishmanial antiagents that is modulated by adherent suppressor cells. We describe a
case of DCL from Peru in a patient who acquired the disease in the department of junin. Parasites were
isolated from the patient’s lesions and characterized using isoenzyme analysis and monoclonal
antibodies.

CASE REPORT

The patient, a 31-year-old female from the department of junin who had never traveled outside peru,
presented with non-ulcerative cutaneous lesions that appeared as plaques and multiple nodules over
her face, neck,a rms, legs, and feet. The disease reportedly started as a small papule on the patient’s
forehead ~ 18 months prior to our initial examination. Approximately 6 months after the appearance of
the papule, 5 ampules (a total of 2,1 g antimony) of meglumine antimoniate were injected in the
primary lesion and 5 ampules (a total of 2,1 g antimony) were injected im. The patient had also treated
the initial lesion by applying an insecticide to it. Neither of these treatments resulted in clinical
improvement of the lesions. Needle aspirates were taken from all lesion sites and inoculated into
diphasic blood agar medium for isolation and growth of parasites. Leishmaniasis positive cultures were
obtained from all lesions aspirated. Intradermally injected leishmanin skin test antigen prepared from
leishmania braziliensis braziliensis failed to produce a delayed hypersensitivity response.

The promastigotes isolated from the lesions were identified by cellulose acetate electrophoresis using
methods described by Kreutzer and co-workers. The isoenzyme patterns of the isolates were the same
as those of the WHO reference strains for L. Mexicana Mexicana (MHOM/BZ/82/BEL21) and
L.m.amazonensis (MHOM/BR/73/M2269) for the enzymes phosphogluconate dehydrogenase (6PGDH)
and mannose phosphate isomerase (MPI) and the same as that of L.m.amazonensis for glucose
phosphate isomerase (GPI). Monoclonal antibodies obtained from Diane McMahon-Pratt (Yale
University) that are specific for the L.mexicana complex (M11; XLV-1D11-E11) and for isolates in an
indirect immunofluorescence assay, confirming that the isolate was L.m.amasonensis.

Glucantime was administered to the patient iv at 20 mg antimony/kg body weught/day for a total 60
days. Treatment was given 5 days a week for 6 weeks (initial course of 30 days), stopped for 7 days,
then administered again for 6 weeks at 5 days a week (2nd course of 30 days). Treatment resulted in
visible improvement of the lesions and a decrease in the number of organisms after 30 and 60 days, but
not complete disappearance of the lesions or the organisms. Organisms were re-isolated from the
lesions after 30 and 60 days of treatment. A leishmanin skin test that was applied on the 20th day of the
2nd course of treatment was negative.

Histological examination of a biopsy taken from 1 lesion on the arm before treatment showed the
presence of large numbers of extracellular and intracellular amastigotes, relatively few lymphocytes,
and a diffuse cellular infiltrate. Another biopsy was taken from a lesion on the forehead on the 20th day
of the 2nd course of treatment. Histological examination showed fewer parasites, fewer macrophages,
and a less diffuse cellular infiltrate than in the pre-treatment biopsy. Most of the amstigotes were
intracellular and the number of lymphocytes was greater than the number of macrophages.

DISCUSSION

Although at least 1 case of DCL has previously been documented from Peru, no details on the clinical
presentation or the causative species were reported. The clinical presentation of the case reported here
did not differ from published descriptions of DCL in the New World and the Old World. Examination of
the biopsy speciments obtained prior to treatment showed a large number of intracellular and
extracellular amastigotes and few lymphocytes, findings consistent with previous histological reports of
DCL.

The causative agent was L.m.amazonensis, as determined by analysis of electrophoretic patterns for
MPI, 6PGDH, and GPI, and by binding of monoclonal antibodies specific for L.m.amazonensis. diffuse
cutaneous leishmaniasis caused by L.m.amazonensis or L.m.mexicana has been reported from the New
World. L.m.amazonensis was the causative agent of 5 cases of DCL in Brazil. Other cases of DCL caused
by L.m.amazonensis have been reported from Bolivia, Brazil, Colombia, and Venezuela. Isolates from 6
DCL patients in Mexico were identified as L.m. mexicana by monoclonal antibodies and isoenzyme
analysis. In Peru, human disease associated with L.m.amazonensis is not common. We have identifie d
isolates from 160 Peruvian leishmaniasis patients and have found only 1 other case of L.m.amazonensis
in a patient with a simple cutaneous lesion (data not shown). Romero and co-workers report that none
of the 26 Peruvian Leishmania isolates they studied by isoenzyme analysis, monoclonal antibody binding
characteristics, and k-DNA hybridization patterns were identified as belonging to the L.mexicana
complex. Grimaldi and co-workers reported that they “typed some Peruvian isolates from the Pasco
forest as L.amazonensis, but doubt has been cast on the true origin of these isolates”. We have
confirmed that L.m.amazonensis is present in Peru and that it can cause DCL in susceptible individuals.

Treatment of the patient with Glucantime at a dosage of 20 mg antimony/kg body weight/day for a total
of 60 days resulted in visible improvement of the lesions and a decrease in the number of parasites, but
not a complete clinical or parasitological cure. Successful treatment of DCL will require the use of more
aggressive therapeutic regimens, novel anti-leishmanial agents, or perhaps the use of combined
immunotherapy and chemotherapy.