Mario Maniscalco1, Giuseppe Noto2, Leonardo Zichichi3 and Stefano Veraldi4,*

1Public Health, Dermatology and Sexually Transmitted Diseases Unit, ASL1, Agrigento, 2Dermatology Unit, Oncological Department, La Maddalena Hospital, Palermo, 3Department of Dermatology, S. Antonio Abate Hospital, Trapani, and 4Institute of Dermatological Sciences, University of Milan, IRCCS Foundation, Policlinico, Mangiagalli and Regina Elena Hospital, Via Pace 9, IT-20122 Milan, Italy. *E-mail: stefano.veraldi@libero.it

Accepted October 16, 2006

Sir,

Cutaneous leishmaniasis (CL) is an infection caused by protozoa belonging to the genus Leishmania (L.). The disease is transmitted by sandflies: Phlebotomus (P.) spp. and Lutzomyia spp. are the most frequently involved. Disease reservoirs are represented by dogs, mice, rats, wild rodents and, more rarely, humans.

CL is very frequent in the Mediterranean Basin, especially in Sicily. L. infantum, transmitted by P. pappatasi, P. perfiliewi and P. perniciosus, is responsible for all cases observed in Sicily. From the clinical point of view, CL in the Mediterranean Basin is usually characterized by a single, polymorphous lesion located on exposed areas, in particular the face, followed by the upper limbs.

In the last few years, we have observed several patients with CL characterized clinically by multiple, monomorphous, slightly inflammatory, papular or papulo-nodular lesions. Some of these lesions appeared as “twin lesions”.

We believe that this presentation represents a new clinical variety of CL, which has been called “multifocal CL” by other authors (1–3). The hypothesis of a new carrier involvement is advanced.

PATIENTS AND METHODS

Over the period 2001 to 2005 we observed 29 patients with CL characterized by multiple lesions. In all patients the diagnosis of CL was based on history, clinical picture, cytological examination of smear scraped from the lesions and histopathological examination. In 7 patients 2 biopsies were carried out. Polymerase chain reaction (PCR) was performed in 24 patients.

RESULTS

The case list comprises 29 Caucasian patients (20 males (69%) and 9 females (31%)), age range 1–84 years (mean age 37.3 years) (Table I). According to clinical history, no patient was previously affected by leishmaniasis. The disease was localized to the head and/or neck in 12 patients, the upper limbs in 12, the trunk in 7 and the lower limbs in 5. The number of lesions in each patient ranged from 2 to 16. All lesions were monomorphous, slightly inflammatory, papular or papulo-nodular (Figs 1–3). Some of them appeared as “twin lesions” (Figs 2 and 3). All patients were immune competent and in good general health.

Fig. 1. Multiple papular lesions.

Fig. 2. Twin lesions on the nose and left cheek.

Fig. 3. Twin lesions on the right forearm.

The histopathological picture of the lesions did not differ from what is usually observed in typical cases of CL. In all investigated patients PCR was positive for L. infantum (see Table I).

Twenty-three patients were treated with local N-methyl-glucamine antimonate (1 peri- and intra-lesional injection/week for 3–6 weeks), either as monotherapy (n = 17) or in combination with cryotherapy (1 application of 10–30 sec per lesion/week for 3 weeks) (n = 3) or oral antifungals (fluconazole or itraconazole) (n = 3). Six patients received cryotherapy, cryotherapy and oral itraconazole, 20% paromomycin ointment or liposomal amphotericin B. All patients recovered. A transitory hyperchromic lesion developed in 2 patients treated with cryotherapy. A 3-month follow-up was negative in all patients.

DISCUSSION

In the last few years we have observed a new clinical variety of CL, which Paradisi et al. (1) recently named “multifocal CL”.

This clinical variety of CL is characterized by multiple, monomorphous lesions. These lesions are very similar to each other, the only difference being their size. Furthermore, they usually appear as papules or small nodules, with very mild erythema, although this may be completely absent. Satellite papules are not uncommon in areas endemic for leishmaniasis, but often erupt after the start of the specific therapy.

CL caused by L. infantum is often characterized by atypical clinical features (4, 5). A relationship between genomic and clinical polymorphism has been suggested (6). However, multifocal CL might be caused by species of sandflies that are different from P. pappatasi, P. perfiliewi and P. perniciosus. It is known that these sandflies are lone arthropods that do not live in swarms. Furthermore, sandflies usually sting just once when feeding. It is therefore possible that multifocal CL is caused by sandflies that live in swarms (e.g. multiple lesions are the clinical results of multiple stings caused by several sandflies) or by a single sandfly that stings several times (2). Another fact that supports the hypothesis of a new carrier in multifocal CL is that all patients were observed in a well-defined area of Western Sicily (Agrigento, Palermo and Trapani provinces). In addition, all patients who were observed by one of us (S.V.) in Milan (Northern Italy) contracted the disease in the same area. However, we cannot exclude the possibility that multifocal CL may be caused by a mutant Leishmania spp. or by an individual atypical immune response to the protozoan.

A sub-variety of multifocal CL is represented by “twin lesions”. These are usually constituted by a couple of papules, clinically almost identical, very close to each other (0.5–1.5 cm apart). Sometimes, only very small differences in size are visible.

Various kinds of treatments were used in these patients, on the basis of age, general health, compliance, location and morphology of the lesions. A complete response was observed in all patients.

REFERENCES

1. Paradisi A, Capizzi R, Zampetti A, Proietti I, De Simone C, Feliciani C, Amerio PL. Atypical multifocal cutaneous leishmaniasis in an immunocompetent patient treated by liposomal amphotericin B. J Infect 2005; 51: e261–e264.

2. Del Giudice P. Multifocal cutaneous leishmaniasis. J Infect 2006; in press.

3. Paradisi A, Capizzi R, Zampetti A, Proietti I, De Simone C, Feliciani C, Amerio PL. Multifocal cutaneous leishmaniasis. J Infect 2006; in press.

4. Grevelink SA, Lerner EA. Leishmaniasis. J Am Acad Dermatol 1996; 34: 257–272.

5. Del Giudice P, Marty P, Lacour JP, Perrin C, Pratlong F, Haas H, et al. Cutaneous leishmaniasis due to Leishmania infantum. Case reports and literature review. Arch Dermatol 1998; 134: 193–198.

6. Guerbouj S, Guizani I, Speybroeck N, Le Ray D, Dujardin JC. Genomic polymorphism of Leishmania infantum: a relationship with clinical pleomorphism? Infect Genet Evol 2001; 1: 49–59.