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Ulcerated disseminated cutaneous leishmaniasis associated with vitiligo, hypothyroidism, and diabetes mellitus in a patient with Down syndrome

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Ulcerated disseminated cutaneous leishmaniasis associated with vitiligo, hypothyroidism, and diabetes mellitus in a patient with Down syndrome
Shahin Aghaei MD1, Rahmat Salmanpour MD1, Farhad Handjani MD1, Ahmad Monabati MD2, Nazila Mazharinia MD1, and Ladan Dastgheib MD1
Dermatology Online Journal 10 (2): 21

Department of Dermatology1 and Department of Pathology2, Shiraz University of Medical Sciences, Shiraz, Iran.


We report a 35-year-old man who was referred to our dermatology department with multiple, nodular, ulcerated, and crusted lesions disseminated on the face, trunk, and extremities. He has a known diagnosis of Down syndrome. The past medical history also included vitiligo (for 20 years), hypothyroidism (for 2 years), and type-II diabetes mellitus (for 3 months). Direct smear of an ulcer was positive for leishmania. Skin biopsy confirmed the diagnosis. A leishmanin skin test was negative. Polymerase chain reaction (PCR) from two separate skin biopsies demonstrated the presence of Leishmania major. To our knowledge, this is the first report of disseminated cutaneous leishmaniasis (DCL) caused by L. major in Iran, and also the first report of association between DCL with Down syndrome, vitiligo, hypothyroidism, and diabetes mellitus.

Disseminated cutaneous leishmaniasis (DCL) is a rare manifestation of human leishmaniasis; it is characterized by multiple, slowly progressive nodules or plaques without ulceration, involving almost the entire skin surface. It is suggested that DCL results from a lack of cell-mediated immunity to leishmania antigen, leading to uncontrolled parasite growth.

Clinical synopsis

Figure 1 Figure 2
Preoperative view of the patient, front view (Fig. 1).
Preoperative view of the patient, back view (Fig. 2).

Figure 3
Several leishmanial skin lesions over the upper and lower extremities.

A 35-year-old man was referred to the dermatology department of Shiraz University of Medical Sciences with a 6-month history of several skin lesions on the scalp, face, trunk, and extremities (Figs. 1, 2, and 3). The patient had raised, well-defined, ulcerated, and crusted nodules of variable size, that were without significant symptoms such as itching, pain, or anesthesia.

The patient was known to have Down syndrome with characteristic morphologic features that had been recognized in infancy. His major manifestations were mental retardation, flat faces with increased interocular distance (hypertelorism), mild depressed nasal bridge, flat occiput, broad short neck, relatively small mouth with protrusion of the tongue (with difficulty in eating and speaking), and short stature. Chromosomal analysis of karyotype was not required to establish the diagnosis because of apparent characteristic features.

The patient had generalized depigmented patches that were present about 20 years, hypothyroidism of 2 years duration (under daily treatment with 100 µg oral levothyroxine), and type-II diabetes mellitus diagnosed 3 months earlier (under daily treatment with 5 mg oral glibenclamide).

The patient had a low-grade fever and mild malaise. Other than mild diffuse thyromegaly, no organomegaly or lymph node enlargement was detected. No other physical findings were present.

Except for transient leukopenia after glucantime injection, his complete blood count was normal. The baseline erythrocyte sedimentation rate was high (ESR = 71), but after treatment it became normal. Liver, kidney, and thyroid function tests (TSH, T3, and T4) were within normal limits. His fasting blood sugar was under control by glibenclamide (FBS = 105 mg/dl). The patient had no risk factor for HIV; therefore, we did not perform an HIV test.

Figure 4 Figure 5
Histopathology of the lesions (H&E stain). Original magnification 40 × (Fig. 4), and 1000 × (Fig. 5).

We prepared smear and culture from exudates of fluctuant lesions for microbiology; Staphylococcus aureus was found and the patient was treated with intravenous cefazoline (1 g/q 6h for 10 days). After treatment of superinfection, we prepared a direct smear for leishmania, which showed abundant amastigotes outside and within histiocytes. An intradermal skin test for leishmania (Montenegro test) with 0.1 cc of solution was negative after 72 hours.

Two separate skin biopsies were performed. Histological examination of the specimens showed ill-defined nonconfluent granulomas composed of histiocytes and occasional multinucleated giant cells surrounded by numerous plasma cells, lymphocytes, and macrophages. The epithelioid histiocytes were loaded with Leishman bodies. Some of them were free in the tissue (Figs. 4, 5). Polymerase chain reaction successfully amplified L. major DNA from the patient's paraffin-embedded tissue specimen.

Figure 6 Figure 7
Fig. 6 & 7: Photograph of the patient after treatment.

Treatment with intramuscular injections of meglumine antimoniate (Glucantime 60 mg/kg or 3 vials/day) was initiated, but after 7 days the patient became leukopenic (white blood cells less than 3000/ml); we continued the treatment with one vial of the drug as intramuscular injection daily plus oral ketoconazole (200 mg/q 8h) for 20 consecutive days. The patient improved with some depressed scars (Figs. 6, 7).


Disseminated (diffuse) cutaneous leishmaniasis (DCL) is an anergic variant of localized-cutaneous leishmaniasis (LCL), in which lesions are disseminated, resembling lepromatous leprosy [1]. The disease usually begins with an initial primary lesion and then disseminates to involve other areas of the skin. The lesions are nonulcerative nodules full of parasites, and are often scattered over the limbs, buttocks, and face. Unlike lepromatous leprosy, nerve involvement does not occur. The disease does not invade internal organs; however, it responds only partially to treatment and often relapses, becoming chronic [1, 2]. Immunologically, there is a positive antibody response but a negative delayed-type hypersensitivity response to leishmania antigen [2].

In the New World, DCL has been associated with Leishmania pifanoi [3], L. amazonensis, L. mexicana [4, 5], and L. venezuelensis [6]. In the Old World it has been associated with L. aethiopica [1], L. major [7], and L. tropica [8].

Although the lesions are said to be nonulcerative nodules, ulcerated lesions, as were present in our case, have been reported [9].

Thyroid disorders (hypothyroidism, hyperthyroidism, and Graves disease) are frequently present in patients with Down syndrome (DS) [10, 11, 12]. Subtle thyroid abnormalities may occur in patients with DS with no evidence of clinical dysfunction, and further investigation may be necessary to determine whether there is a need for therapeutic intervention [12]. DS is associated with an increased prevalence of numerous dermatological conditions such as pityriasis rubra pilaris, vitiligo [13], alopecia areata, syringoma [14], and elastosis perforans serpiginosa [15].

This is a report of DCL caused by L. major in association with vitiligo, hypothyroidism, and diabetes mellitus in a patient with impaired cellular immunity. Defect in cellular immunity (poor T-cell response to leishmania antigen) may be responsible for dissemination of leishmaniasis [9], such as occurred in our anergic patient.

Unlike visceral leishmaniasis, cutaneous leishmaniasis is uncommonly described in patients with human immunodeficiency virus infection [16].

According to our knowledge, there are no reports of DCL associated with multiple autoimmune disorders such as vitiligo, hypothyroidism, and diabetes mellitus in a DS patient. Also, we did not find any reports of DCL due to L. major from Iran.

Acknowledgment: Written consent was obtained from the patient's family for publication of his details and figures. The authors thank for this consent.


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