Case report: Intralesional or systemic meglumine antimoniate 5 mg Sb5+/kg/day?
Alternatives for the treatment of the elderly with cutaneous leishmaniasis in basic health units05/02/2021
Armando de Oliveira Schubach, Infectologist, MSc, PhD
Maria Cristina de Oliveira Duque, Dermatologist, MSc
Cláudia Maria Valete, Otorhinolaryngol, MSc, PhD
In Brazil, the standard treatment for cutaneous leishmaniasis is performed with meglumine antimoniate at a dose of 20 mg of pentavalent antimony per kilogram of patient weight per day. Due to the toxicity of this medication, treatment in patients over 50 years of age or with renal, cardiac and hepatic comorbidities should be performed with liposomal amphotericin B, available only in centers far from endemic areas. In this article, we report the case of an elderly patient with comorbidities who was successfully treated at a basic health unit with meglumine antimoniate in alternative regimens.
In Brazil, liposomal amphotericin B is the treatment indicated for American cutaneous leishmaniasis (ATL) in patients over 50 years of age or with renal, cardiac and hepatic comorbidities1. Alternatively, it is possible to indicate treatment with intralesional meglumine antimoniate (AM-IL) in elderly patients or with contraindications to the use of BF systemically.2,3 Another possibility when BF at the standard dose of 20 mg Sb5+/kg/day is a risk for patients, is the use of systemic AM 5 mg Sb5+/kg/day, administered continuously or intermittently.1,4-6
Throughout Brazil, the treatment of ACL is usually carried out in basic health units, characterized by a lack of resources and operational difficulties for the management of comorbidities, monitoring of adverse effects and use of medications such as amphotericin B. As a rule, such medication is administered on an inpatient or day-hospital basis, in centers located at great distances from endemic areas.7 Under the existing conditions for the treatment of ACL in basic health units in Brazil, simple, practical therapeutic schemes, effective and safe as AM-IL and systemic AM 5 mg Sb5+/kg/day are desirable.
Recently, Duque et al.8 reported therapeutic success in 27 of 30 patients treated with AM-IL in a basic health unit. In the following report, we describe one of these three patients with an unsatisfactory therapeutic response and the need for new treatment.
A 68-year-old man, weighing 78 kg, hypertensive, with alcohol abuse background, was seen at the Basic Health Unit Primavera, Timóteo, Minas Gerais on 3/2/2016. He had evolved for three months with three cutaneous lesions located on the forehead, lobe of the right ear and right hand (largest lesion, measuring 3.2×2 cm) (Figure). Treatment with AM-IL was initiated and three infiltrations were performed at fortnightly intervals (on days 1, 15 and 30). The total volume administered in each infiltration was 13.5 ml, 9.5 ml and 10 ml, respectively, without adverse effects. During consultations on the 30th and 60th days, the lesions were epithelialized (Figure). On day 120 the patient returned with signs of reactivation of the lesions, in addition to the appearance of five new lesions (one on the mentonian region, one on the left foot, two on the right preauricular region and one on the scalp) (Figure). Systemic AM was initiated 5 mg Sb5+/kg/day (5 mL) IV, intermittently (three series of 10 days interspersed with a 10-day interval without medication). The patient tolerated the treatment well, without adverse effects. The lesions were fully healed on day 240 (Figure) and remained healed and without the appearance of mucous lesions in consultations one and two years after the beginning of the treatment.
We report the case of a patient whose first therapeutic option would be liposomal amphotericin B, due to his age and associated comorbidities. As the patient refused to hospitalize and leave his place of work and home, we chose to start treatment with AM-IL. The patient presented a good initial therapeutic response, with epithelialization of the lesions.8 Three months after the end of the treatment, he returned with the reactivated lesions, in addition to five new lesions, which indicated the systemic treatment with AM 5 mg Sb5+/kg/day of intermittently, 5 in the basic health unit. The treatment was well tolerated and the lesions evolved to full healing, with no mucosal lesions appearing for two years after treatment.
Treatment with AM-IL or systemically 5 mg Sb5+/kg/day employs a total dose of Sb5+ 4 to 10 times lower than that required for systemic treatment with the standard dose of 20 mg Sb5+/kg/day. Consequently, although such therapeutic regimens can cause adverse local and systemic effects, as well as laboratory and electrocardiographic changes, such adverse effects are usually mild to moderate and reversible, without the need to interrupt treatment, even in elderly patients or with contraindications to systemic BF. 2-5.8.9
Whatever the treatment used, there is no way of predicting which patient will remain permanently cured, which one will reactivate the skin lesions, or which one will evolve to the mucosal form10. Therefore, it is recommended that patients be followed for at least two years after treatment, as it is believed that more than half of the reactivations and evolutions for SCI occur during this period1. The arguments that the spontaneous cure of skin lesions or the use of underdoses and local treatments could be responsible for the bad evolution of the disease, they have been losing support in the face of contrary evidence, resulting from the long-term follow-up of patients with spontaneous cure or treated with AM-IL or systemically 5 mg Sb5+/kg/day.9-13
The use of AM-IL or systemic AM 5 mg Sb5+/kg/day, administered continuously or intermittently, may be viable alternatives for the treatment of ATL in basic health units when using the standard dose of 20 mg Sb5+/kg/day is a risk for patients.
- Brasil. Ministério da Saúde (MS) Secretaria de Vigilância em Saúde (SVS). Departamento de Vigilância das Doenças Transmissíveis. Manual de Vigilância da Leishmaniose Tegumentar [Internet]. Brasília: SVS/MS; 2017. 189 p. [cited 2020 August 5]. Available from: http://bvsms.saude.gov.
- Duque MCO, Quintão JJ, Gonçalves LF, Gomes C, Almeida HL, Silveira ES, et al. Treatment of cutaneous leishmaniasis with intralesional meglumine antimoniate at a primary care unit in Brazil. Rev Med Saúde Brasília. 2017;6(2):240-8.
- Vasconcellos E, Pimentel MIF, Schubach AD, de Oliveira RDC, Azeredo-Coutinho RB, Silva FDC, et al. Short Report: Intralesional Meglumine Antimoniate for Treatment of Cutaneous Leishmaniasis Patients with Contraindication to Systemic Therapy from Rio de Janeiro (2000 to 2006). American Journal of Tropical Medicine and Hygiene. 2012;87(2):257-60.
- Cataldo JI, Conceição-Silva F, Antonio LF, SchubachAO, Marzochi MCA, CM, et al. Favorable responses to treatment with 5 mg Sbv/kg/day meglumine antimoniate in patients with American tegumentary Rev Soc Bras Med
- Vasconcellos ECF, Schubach AO, Valete-Rosalino CM, Coutinho RS, Conceição-Silva F, Salgueiro MM, et al. American tegumentary Geriatr Soc. 2010;58:614-6.
- Saheki MN, Lyra MR, Bedoya-Pacheco SJ, Antonio LF, Pimentel MIF, Salgueiro MM, et al. Low versus high dose of antimony for American cutaneous leishmaniasis: A randomized controlled blind non-inferiority trial in Rio de Janeiro, Brazil. PLoS One. 2017;12(5):e0178592.
- Comparative study on liposomal amphotericin B and other therapies in the treatment of mucosal leishmaniasis: A 15-year retrospective cohort study. PLoS One. 2019;14(6):e0218786.
- Duque MCO, Quintao Silva JJ, Soares PAO, Magalhaes RS, Horta APA, Paes LRB, et al. Comparison between systemic and intralesional meglumine antimoniate therapy in a primary health care unit. Acta Tropica. 2019;193:176-82.
- Terceiro BRF, Schubach AO, Moreira JS, Martins ACC, Bom-Braga FP, Costa DCS, et al. Low-dose meglumine antimoniate may be a safety treatment for mucosal leishmaniasis in the elderly Revista de Medicina e Saúde de Brasília. 2021 (in press).
- Brahim LR, Valete-Rosalino CM, Antonio LF, Pimentel MIF, Lyra MR, Paes LEC, et al. Low dose systemic or intralesional meglumine antimoniate treatment for American tegumentary centre in Rio de Janeiro, Brazil (2001-2013). Mem Inst Oswaldo Cruz. 2017;112(12):838-43.
- Cota GF, de Sousa MR, Fereguetti TO, Saleme PS, TK, Rabello A. The Cure Rate after Placebo or No Therapy in American Cutaneous Leishmaniasis: A Systematic Review and Meta-Analysis. PLoS One. 2016;11(2):e0149697.
- Oliveira-Ribeiro C, Pimentel MIF, Oliveira RVC, Fagundes A, Madeira MF, Mello CX, et al. Clinical and laboratory profiles of patients with early spontaneous healing in cutaneous localized leishmaniasis: a historical cohort study. BMC Infect Dis. 2017;17(1):559.
- Blum J, Lockwood DN, Visser L, Harms G, Bailey MS, Caumes E, et al. Local or systemic treatment for New World cutaneous leishmaniasis? Re-evaluating the evidence for the risk of mucosal leishmaniasis. Int Health. 2012;4(3):153-63.