Severe Inflammatory and Disseminated Cutaneous Leishmaniasis in a Pregnant Woman: A Case Report from Portoviejo, Ecuador

Introduction

Cutaneous leishmaniasis (CL) is a parasitic disease caused by protozoa of the genus Leishmania. It is a zoonosis or anthroponosis, whose reservoirs are wild mammals present in tropical and subtropical areas. It is transmitted by dipterous insects of the genus Phlebotomus in the Old World and Lutzomyia in the New World. Leishmaniasis affects approximately 112 million people worldwide, with an annual incidence of 2 million, and around 350 million people are at risk [1,2]. In Ecuador, 8 of the already described 20 species of Leishmania affecting human have been registered, causing around 2000 cases per year in different geoecological endemic regions [3]. The 8 species are as follows: L. (Viannia) braziliensis, L. (V.) panamensis, L. (V.) guyanensis, L. (V.) naiffi, L. (V.) lainsoni, L. (Leishmania) mexicana, L. (L.) amazonensis, and L. (L.) major-like. The mammals incriminated as probable reservoirs in Ecuador are Sciurus vulgaris granatensis (common squirrel), Potos flavus (kinkajou, cuzumbo), Tamandua tetradactyla (oso hormiguero arborícola; found naturally infected with L. (L.) amazonensis); Rattus (black rat; naturally infected with L. (L.) Mexicana); and canis familiaris (mongrel dog; naturally infected with L. (L.) mexicana and L. (V.) panamensis) [3]. Currently, 73 species of sand flies have been registered in Ecuador [4–6]. There are 4 Ecuadorian species already incriminated as probable vectors: Lu. trapidoi and Lu. gomezi (naturally infected with L. (V.) guayanensis/panamensis), Lu. ayacuchensis (naturally infected with L. (L.) Mexicana), and Lu. tortura (naturally infected with L. (V.) naiffi) [6,7]. There is a wide range of clinical presentations of leishmanial cutaneous lesions in humans in Ecuador, varying from classic typical small or large ulcers, unique or several and disseminated, to nodular, verrucous, impetiginized, and relapsing chronic lesions (recidiva cutis), probably due to different causative Leishmania agents and clinical evolution [6,8–10]. To the best of our knowledge, there is no available information about the clinical picture of CL during pregnancy in Ecuador, and that is probably due to the fact that leishmaniasis in pregnant women usually does not differ in most cases from other Ecuadorian CL patients. However, since pregnancy is associated with physiological cell immunodeficiency [11,12], attention should be paid to the clinical presentation and evolution of the disease in some cases. The present study is probably not the worst case of such a type but it is the first report of an atypically aggressive CL observed in a pregnant woman from Ecuador.

Case Report

PHYSICAL EXAMINATION AND PRESUMPTIVE CLINICAL DIAGNOSIS:

At the time of the clinical evaluation, we found a young healthy looking woman, weighing 63 kg, who had a total of 7 crusty elevated ulcers distributed among the hands (1 on the left annular finger and 1 on the dorsal area of right hand), and 5 on the left front axillary line area. All lesions were inflamed and painful, with surrounding erythema and edema, and those on the scapular area had many satellite papules. Because of pain, the patient could not tolerate anyone touching on or around the lesions. The lesion on the annular left finger (20 mm in diameter) was a painful ulcer with very elevated thick borders and a big granuloma inside (Figure 2A). The lesion on the dosal area of the right hand was also an elevated crusty ulcerous plaque, with a diameter of about 4 cm (Figure 2B). In the left axillary line area, 5 crusty lesions (20–40 mm) were the most painful and inflamed of all. As already mentioned, there were also a lot of satellite papules growing, to become new ulcers (Figure 2C). There were no systemic signs or symptoms, but the patient was suffering because of painful lesions and moved around very slowly. Aside from the abovementioned situation, the patient was healthy and did not present any other problem. Vital signs were normal, as were complete laboratory biological tests, including HIV serology. She did not have any important personal or family clinical background. This was her first pregnancy.

Based on our experience, she had what are considered the 3 criteria that are highly suspicious of leishmaniasis: (1) exposure to the vector (epidemiological point), (2) evolution, and (3) clinical aspect of lesions [1]. Related to those criteria, she lived in an urban area but worked in a periurban area, very close to a CL-endemic area (exposed to the bite of vector sand flies), the clinical evolution was typical of CL (prior to inflammatory complication), and the early clinical aspect (prior to inflammatory complication) was also typical of CL. Regarding severity, the disease is considered severe if any one of the following criteria are fulfilled: (1) the etiologic agent is L. (V.) braziliensis, no matter the size, number and location of the lesions; (2) a single lesion is on the face or over any articulation, no matter the etiologic agent, size, and number of lesions; (3) the main diameter of a lesion is larger than 30 mm, no matter the etiological agent, and location; (4) there are more than 2 lesions, no matter the etiological agent, size, and location; (5) there is secondary bacterial or fungal infection, no matter the etiological agent, number of lesions, size, and location; (6) there is lymphatic and/or ganglionic compromise, no matter the etiological agent, size, number, and location; (7) the patient has one of the known complications of CL, such as metastasic mucocutaneous lesions, recidiva cutis, or diffuse cutaneous lesihmaniasis (DCL); and (8) the patient belongs to a vulnerable group (pregnancy, organic dysfunction, elderly, or lactancy) [1].

Our patient met 3 of these criteria for severe leishmaniasis: lesion on articulation (finger), number, and size of lesions, and pregnancy.

LABORATORY DIAGNOSIS:

Because of the painful inflammatory lesions, it was not convenient to take a biopsy sample, and the intradermal Leishmania test was no longer available in Ecuador; also, the intradermal test is not recommended for testing people living on or near endemic areas for Leishmania transmission, because of false positives [13]. The usual method for direct parasitological diagnosis of leishmaniasis in Ecuador is the stained smear, or frotis [14]. For this purpose, the lesions and the adjacent skin were cleaned and sterilized with an antiseptic. Several samples were carefully taken out of lesions and stained with Giemsa. All of them were clearly positive, showing a moderate amount of Leishmania spp. amastigotes and parasited macrophages (Figure 3). Once the parasitological examination was confirmed and related to the clinical situation, the diagnosis was established as severe CL. According to the permanent monitoring of the Leismania spp. transmitted in Ecuador, the circulating species predominant in the area where the patient lived was identified as L. (V.) guyanensis [15–19].

FINAL DIAGNOSIS:

After epidemiological, clinical, and severity evaluations, parasitological confirmation established the final diagnosis as severe inflammatory and disseminated CL [9,20–24].

TREATMENT:

Due to her clinical painful condition, it was not possible to wait until childbirth for treatment. However, because of her pregnancy, the patient was at risk for conventional antileishmanial treatment; therefore, a decision was needed on how to best handle her case.

The first drugs of choice for treatment of CL are pentavalent antimony (meglumine antimoniate, intramuscular or intravenous, 10–30 mg/kg/day) for 20 days, and the second drug of choice is Miltefosine (1.5–2.5 mg/kg/day) for 28 days. Alternatives are intralesional (intradermic injection) treatment with meglumine antimoniate, direct application of liquid nitrogen (cryosurgery), and the use of liposomal Amphotericin B [1,13]. Considering the patient’s pregnancy, a final option was to avoid the use of specific antileishmanial treatment with antimonials or Miltefosine and to maintain the lesions with local treatment and ointments with antibiotics to prevent secondary bacterial infections until after delivery. Finally, we decided to avoid the use of specific antileishmanial treatment and to immediately perform maintenance therapy, using a topical mild anti-inflammatory ointment (diclofenaco dietilamonio) to relief pain and inflammation (twice a day for 5 days), topical strong triple antibiotic ointment (containing polymyxin B, bacitracin, and neomycin) to prevent or control secondary bacterial infections (twice a day for 5 days), and local treatment with liquid nitrogen (topically on each lesion every 10 days, for 3 applications in 30 days) as soon as inflammation disappeared. Liquid nitrogen has been used as a good alternative treatment for CL for vulnerable individuals [25], as has thermotheraphy [26,27].

COLATERAL EFFECTS:

Because of the type of treatment – cryotherapy plus topical antibiotics and anti-inflammatory ointment – used in this case, there were no collateral undesired effects during treatment or follow-up.

TREATMENT RESULTS:

All the lesions started to improve after the second week of initial treatment. Inflammation disappeared, and healing process was evident in the fourth week. After day 30, the percentage of healing was between 70% and 90%. Complete healing was reached 60 days after the end of treatment. At that time, lesions in the left index finger and on the dorsal part of right hand had elevated bordered scars; the others, on the right scapular, showed lightly elevated bordered scars. On day 90 after treatment, just before childbirth, all scars were completely flat (Figure 4). Therefore, the treatment led to satisfactory healing, without the use of an antileishmanial drug, which could be administrated later on, after delivery.

FOLLOW-UP:

After initiation of the alternative treatment mentioned above, clinical and laboratory evaluations showed a normal condition of the patient. Controls were done for every month until delivery, for a period of 3 months. The child was born naturally, without any clinical alterations. After 1 year, there was no reactivation of lesions, and parasitological examination of samples from healed borders of lesions demonstrated no parasites. Thus, the patient was not given conventional antileishmanial treatment with drugs such as antimonials. The last parasitological examination, 18 months after the initial alternative treatment of cryotherapy, revealed negative results for the Leishmania parasites.

Discussion

LIMITATIONS:

The only limitation presented was that the patient with CL could not receive antimonial treatment. Therefore, an alternative treatment, local cryotherapy, was used, along with anti-inflammatory ointment and a topical antibiotic.

Conclusions

ETHICS APPROVAL:

This study was reviewed and approved by the Research Council of the Faculty of Medical Sciences of the Catholic University of Santiago from Guayaquil and had ethical approval from the aforementioned.