Two cases of primary endonasal leishmaniasis in Sardinia (Italy)
Dermatology Department of Cagliari University, Cagliari, Italy. email@example.com
Leishmaniasis is an endemic protozoan infection in Sardinia, one of the major islands of the Mediterranean Basin. We report two cases of endonasal primary Leishmaniasis, which is a very rare event in adult men who are immunocompetent, born in, and residents of Sardinia. The diagnosis was confirmed by the presence of intra and extracellular Leishmania amastigotes in the histological smear. Isoenzymatic characterization identified Leishmania infantum zymodeme MON-111 in both cases. Laboratory and instrumental investigations excluded visceral involvement. Treatment with meglumine antimoniate (Glucantim®) intralesional administration, 1ml weekly for 4-5 weeks, led to complete resolution. The unusual location is likely a reflection an uncommon site of inoculation of the protozoa, transmitted by flying vectors. The patients were a shepherd and a farmer, respectively, both professions at high risk of infection because of their habits of sleeping outdoors under trees or in country cottages during spring and summer and exposed to sand fly bites. Although mucosal involvement and infection by Leishmania infantum, a potential cause of visceral leishmaniasis, the Sardinian patients experienced a benign disease course considering muco-cutaneous forms described in the New World. Differential diagnosis and early detection are necessary in order to start effective treatment and prevent more serious complications.
We report two cases of primary endonasal leishmaniasis, which in immunocompetent subjects is extremely rare . In fact, although utaneous leishmaniasis is a relatively frequent disease in the Mediterranean basin, with an incidence in Sardinia of approximately 0.16/1000 inhabitants (a hypo-endemic trend), mucosal surfaces are usually spared [1, 2, 3, 4, 5]. Shepherds, farmers, and people who live and work in the country, irrespective of gender or age, are those primarily affected. Most cases in Sardinia are caused by Leishmania infantum, the principle vectors being Phlebotomus perniciosus (80%) and Phlebotomus perfiliewi (20%). The main reservoirs are dogs and to a lesser degree rodents . Symptoms appear following an incubation period of between two and four weeks, generally with a single nodule.
Case number 1. A 52-year-old shepherd was referred to our center from an ENT surgeon who examined him for recurrent epistaxis. The patient reported no illness worthy of mention except for moderate hypertension treated with angiotensin converting enzyme (ACE) inhibitors. Clinical examination revealed a bright red, 1 cm nodule located in the anterior part of the left cartilaginous septum, which bled easily, was moderately infiltrated, and covered by serosanguinous crusts (Fig. 1). Endoscopy of the nasal cavity and a facial X-ray excluded the presence of further lesions. No other pathological conditions were present at other cutaneous or internal sites by physical examination or screening blood tests. Chest X-ray, ECG, and cardiological checks were all negative.
A lesional smear stained with GIEMSA excluded the presence of neoplastic cells and highlighted numerous intra- and extracellular Leishmania. A biopsy revealed a dense infiltration of lymphocytes, plasma cells, rare eosinophils, and abundant histiocytes with numerous Leishmania present in the cytoplasm as well as in groups outside the cells (Fig. 2). Protozoa typing identified the Leishmania infantum Zymodema Montpellier 111. Because of the unusual site of Leishmaniasis further checks were carried out to exclude visceral localization. Liver scan, abdominal CT, and bone marrow biopsy all were within normal ranges. Humoral and cell-mediated immunity were normal; hepatitis and HIV tests were negative.
Primary endonasal leishmaniasis was diagnosed based on clinical and laboratory test results. Therapy was started with meglumine antimoniate intralesional infiltrations (300 mg/ml), approximately 1 ml once a week for five weeks. The solution was infiltrated until the whole lesion turned white. Maximum infiltration dosage was 1.3 ml. Full resolution was obtained and no recurrence has occurred after three years. No side effects were experienced, except for moderate transitory pain at the infiltration site.
Case number 2. The second patient is a 71-year-old farmer affected for five months by a growth within the left nasal vestibule, causing a sense of obstruction and respiratory difficulty, rhinorrea, and epistaxis. The patient was generally in good health, but had undergone a coronary bypass surgery in 2002 for ischemic cardiopathy.
Anterior rhinoscopy revealed a hard erythematosus, polypoid, non-ulcerated and painless, 1.5 cm diameter nodule located on the mucous membranes of the left nasal vestibule, about 0.5 cm from the free edge of the nose. Moderate edema of the upper lip was also present (Fig. 3). Physical examination, chest X-ray, CBC, and general chemisty screening tests were all within normal ranges. The ECG and strength test performed revealed good cardiac function. A cytological smear stained with GIEMSA revealed numerous intra- and extracellular Leishmania. A biopsy confirmed the protozoan infection and the isoenzymatic characterization identified Leishmania infantum zymodeme MON-111. Visceral involvement was excluded by means of a liver scan, an abdominal CT, and a bone marrow biopsy. Serology for hepatitis and HIV infection were negative.
Primary endonasal leishmaniasis was diagnosed and meglumine antimoniate intralesional infiltrations (300 mg/ml), approximately 1 ml, were performed once weekly with full recovery after four weeks. There has been no recurrence after a one-year follow-up. Pain at site of infiltration was the only side effect experienced.
The most common form of cutaneous leishmaniasis in the Mediterranean basin, of which Sardinia is a major island, is the "oriental sore" with a single, non-ulcerated nodule. In most cases it is localized at exposed sites that are subject to sand fly bites. Mucous membrane localization of leishmaniasis is not frequent and the few reported cases concern immunocompromised patients. Nevertheless, Leishmania infantum Zymodema Monpellier 111, which is the causative agent frequently isolated in our region, might have an invasive potential and has been found in uncommon sites, such as genital and labial mucous or semi-mucous regions with atypical presentation [3, 4, 5].
To our knowledge these are the first descriptions of primary endonasal leishmaniasis in immunocompetent subjects in Italy, and in particular in Sardinia. Our patients were born and live in towns 10 km apart in the middle of southern Sardinia where there is an elevated concentration of human and animal leishmaniasis. Their respective professions, shepherd and farmer, put them at high risk of infection. Exposure to sand fly bites is common because they often sleep outdoors under trees or in country cottages during spring and summer. Leishmania infantum Zymodema Monpellier 111 is the causative agent normally isolated in our region. This organism has been found in lesions localized in uncommon sites, such as mucous membranes or semi-mucous membrane regions, with atypical clinical presentation [3, 4, 5]. Contrary to the invasive and destructive leshmaniasis characteristic of New World muco-cutaneous Leishmaniasis, the nasal localization in our patients did not cause septum perforation or affect other organs. Furthermore, the excellent response to therapy suggests a low virulence of the L. infantum strains in Sardinia. The rapid recovery obtained with the intralesional injections using meglumine antimoniate, confirm that in localized forms of leishmaniasis this procedure is the treatment of choice. In fact, the intralesional use of pentavalent antimony salts has the advantage of an excellent recovery percentage, good tolerance, absence of side effects, and low cost .
Acknowledgement: The Authors are grateful to Mark Weathon for the original manuscript translation in English.
References1. Benmously-Mlika R, Fenniche S, Kerkeni N, Aoun K, Khedim A, Mokhtar I. Primary Leishmania infantum MON-80 endonasal leishmaniasis in Tunisia. Ann Dermatol Venereol. 2008 May;135(5):389-92. French. PubMed [PubMed].
2. Bettini S, Gramiccia M, Gradoni L, Biggio P, Loi R, Cottoni F, Pau M, Atzeni MC. Leishmaniasis in Sardinia. IV. Epidemiological appraisal of cutaneous leishmaniasis and biochemical characterization of isolates. J Trop Med Hyg. 1990 Aug;93(4):262-9. PubMed [PubMed].
3. Kharfi M, Fazaa B, Chaker E, Kamoun MR. Mucosal localization of leishmaniasis in Tunisia: 5 cases. Ann Dermatol Venereol. 2003 Jan;130(1 Pt 1):27-30. French. PubMed [PubMed].
4. Ferreli C, Atzori L, Zucca M, Pistis P, Aste N. Leishmaniasis of the lip in a patient with Down's syndrome. J Eur Acad Dermatol Venereol. 2004 Sep;18(5):599-602. PubMed [PubMed].
5. Aste N, Pau M, Aste N, Biggio P. Leishmaniasis of the prepuce. J Eur Acad Dermatol Venereol. 2002 Jan;16(1):93-4. PubMed [PubMed].
6. Aste N, Pau M, Ferreli C, Biggio P. Intralesional treatment of cutaneous leishmaniasis with meglumine antimoniate. Br J Dermatol. 1998 Feb;138(2):370-1. PubMed [PubMed].
© 2009 Dermatology Online Journal