Leishmaniasis Recidiva Cutis (LRC) is a rare variant of tegumentary Leishmaniasis (LT). Also known as metaleishmaniosis, lupoid leishmaniasis or chronic tuberculoid leishmaniasis in the old world. It is a peculiar form that denotes refractoriness to the treatment [1,2]. Until the year 1976 there were only reports in the Middle East, currently there are still few reports in America [3]. LRC is characterized by the presence of nodular or verrucous lesions, initially isolated, and then confluent around or within the scar of a previous Leishmania lesion, which appears to be late and of long duration [4]. Less commonly, concurrent lesions occur [2].

2.       Case report

A 52-year-old female patient from the center-west of Brazil presented with one year and 6 months of evolution of a lesion who appeared after visiting the rural area. She noticed a papular lesion in the left calf, which evolved centrifugally with central atrophy, without ulceration, with crusty active borders. In the evolution, two more lesions appeared, distal to the previous lesion, in the pre-tibial region and left foot, and another lesion on the right foot (Figure 1), with pain and purulent collection sparse from the lesion's edges.

The diagnosis of the LRC was laborious. The histopathology showed inconclusive, with peseudoepitheliomatous hyperplasia of the epidermis, dermal lymphohistiocytic infiltrate and with giant cells, constituting a loose granulomatous process, but showing no pathogens. Direct research and culture for Leishmania also did not contribute to the diagnosis, because both presented negative in two samples. Direct mycological examination and culture for fungi were both negative either. The Montenegro Intradermal Reaction (IDRM) showed strongly positive (62 x 82 mm) and Tuberculin Skin Test (PPD) with strong reactor (14 mm). Lastly, Immunohistochemistry was performed for infectious agents on the biopsy fragment, being negative for fungi and mycobacteria. However, Immunohistochemistry for Leishmania was positive, finally concluding the diagnosis (Figure 2).

The treatment of this case was a challenge, because different therapeutics were required. Firstly, the patient was treated with two cycles of N-methylglucamine antimoniate intravenously (15 mg Sb + 5 / kg / day), with partial resolution of the primary lesion and complete resolution of the others. Remaining active areas of the primary lesion received 5 sessions of intralesional N-methylglucamine antimoniate, each session with direct intradermal injection of 2 ml of the drug without dilution, distributed throughout the lesions, demonstrating good response, but with a single resistant area at the apical edge. Because of the localized remaining lesion, and considering the other areas were in complete remission, the concern regarding the re-exposure of the patient to the toxicity of a new systemic treatment, and due to the known resistance of this clinical form, surgical excision of the persistent site was proposed. Then, excision with a transposition flap was successfully performed (Figure 3). The patient has been under follow-up for 4 years, with no evidence of relapse.

3.       Discussion

LRC is a rare form of LT, with specific clinical and evolution [3]. Differential diagnoses are cutaneous tuberculosis, granuloma annularis, verrucous lupus erythematosus, sarcoidosis and deep mycoses, among others [1]. There are few reports of LRC, and although the pathophysiology is not fully elucidated, there are some hypotheses to explain it: antibodies in residents of endemic areas - where continued exposure would cause antigenic stimulus; the species of Leishmania involved; irregular treatments with low doses; and the host immunity profile [3,5,6].

Despite the hypothesis of genetic variability among species as a risk factor, and genetic mutations to explain treatment failure, no specific genetic polymorphism has been related as a risk factor for LRC [7]. Hypersensitivity to Montenegro Intradermal Reaction test (IDRM), histopathology and immunohistochemistry point to LRC to be a late reaction to the persistence of parasites in the previous lesions [8]. Hypersensitivity to IDRM defines LRC as a hyperergic variant, and denotes a considerable degree of sensitization of the host to the parasite, with marked cellular immunity, but insufficient to eradicate the infection [4,9,10]. Histopathology shows granuloma that may be indistinguishable from cutaneous tuberculosis, in addition to pseudoepitheliomatous hyperplasia; the presence of Leishmanias on histopathology were not reported since ancient reports.

The Leishmania encounter in the direct examination is the gold standard in LT, and it has become routine for its simplicity and specificity, but it requires an experienced and persistent professional: the chance of finding the parasite is inversely proportional to the evolution time of the injury, being rare after one year, as in this case [11-13]. The detection of amastigotes in formalin-fixed and paraffin-embedded sections has also become routine, but cases such as LRC often do not demonstrate parasites [14-17]. Culture techniques are sensitive; however, they are labor-intensive, require sophisticated laboratory and professional structure, may exhibit variations in efficacy between culture media, and the risk of contamination is a problem [11-13]. The exams such as indirect immunofluorescence reaction and enzyme-linked immunosorbent assay may express the level of circulating antibodies [3]. Immunohistochemistry demonstrates success in the diagnosis of LT and has led to a great advance, which motivates its frequent use for the diagnosis of infectious-parasitic diseases [18-22].

Few cases of LRC have been well documented. Most of the reports present only parasitological evidence, without identification of the agent, which must be done with biochemical and molecular techniques. As LRC occurs predominantly in poor countries, resources are lacking for the realization of these techniques. L (L.) braziliensis, L. Viannia peruviana, Leishmania (Viannia) panamensis, L. (L.) mexicana and L. (L.) major-like have already been identified as agents in the new world; L. (L.) tropica and rarely L. (L.) major in the old world [7]. Treatment is a challenge even in endemic areas [3]. The challenge in establishing a correct diagnosis of this clinical form is associated with difficulties in offering therapeutic regimens with alternative injectable medications, such as Amphotericin B or liposomal Amphotericin B, and ends in the lack of skilled manpower in the clinical management of patients who evolve with this evolutionary form [3,7]. LRC is often resistant to conventional therapies. Treatment options include systemic therapy with good response to high doses of meglumine antimoniate (50 mg / kg per day) parenterally, alone or in combination with allopurinol; amphotericin B; intralesional infiltration with antimonials; cryosurgery and exeresis [3,23]. Many studies have shown a good response to multidrug therapy [7].

4.       Conclusion

By this study, it can be concluded that LRC is a rare disease and its treatment can be challenging, since sometimes it is necessary to associate different types of therapeutics. The option for surgical treatment was made by resistance to previous treatments, the desire to avoid the side effects of long systemic treatments and to reduce the source of parasites, which could lead to the spread to other areas in the future. The patient described was diagnosed for one year with a progressive evolution of the condition. Her detailed investigation and the care in carrying out a treatment specifically directed to the disease were successful in achieving the remission, associating clinical and surgical treatment. Then, the main finding of this case-report is that LRC is an old, but rare disease, and its treatment can be arduous, therefore doctors from endemic areas should be aware of this unusual clinical form and have at their disposal combinations of local and systemic treatments, which may be necessary for the cure of the patient.