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American Tegumentary Leishmaniasis in Older Adults: 44 Cases Treated with an Intermittent Low‐Dose Antimonial Schedule in Rio de Janeiro, Brazil

2010; Wiley; Volume: 58; Issue: 3 Linguagem: Inglês

10.1111/j.1532-5415.2010.02747.x

1532-5415

Érica de Camargo Ferreira e Vasconcellos, Armando de Oliveira Schubach, Cláudia Maria Valete‐Rosalino, Renata de Souza Coutinho, Fátima Conceição‐Silva, Mariza de Matos Salgueiro, Marcelo Rosandiski Lyra, João Soares Moreira, Rilza Beatriz Gayoso de Azeredo-Coutinho, Maria Inês Fernandes Pimentel, Sérgio Roberto Mortari, Maria de Fátima Madeira, Leonardo Pereira Quintella, Cibele Baptista, Mauro Célio de Almeida Marzochi,

Research on Leishmaniasis Studies

To the Editor: American tegumentary leishmaniasis (ATL) is a disease affecting the skin and mucosae caused by protozoans of the genus Leishmania transmitted by the bite of female sandflies. Cutaneous leishmaniasis (CL) presents mainly as skin ulcers at exposed body sites. Mucosal leishmaniasis (ML) manifests as chronic and destructive lesions of the nasal, oral, pharyngeal, and laryngeal tissues.1 Pentavalent antimonials are the first-line treatment for ATL. Reports of pentavalent antimonial toxicity include renal tubular dysfunction; cardiac, hepatic, pancreatic, and hematological alterations; and even death.2-6 Adverse effects (AEs) are frequent, and interruption is sometimes needed in patients aged 60 and older, even those receiving low-dose treatment. Observing that lesions continued to heal during withdrawal, it was decided to evaluate the safety and efficacy of an intermittent low-dose meglumine antimonate (MA) regimen for ATL in the elderly. A study of a case series of 44 patients with ATL aged 60 to 92 (median 69), 27 men and 17 women, followed between September 2000 and December 2005 at the outpatient clinic of the Leishmaniasis Surveillance Laboratory (LabVigileish), Evandro Chagas Clinical Research Institute (IPEC), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil, was performed after the approval of the Research Ethics Committee of IPEC, FIOCRUZ. All included patients signed an informed consent form. Thirty patients probably acquired the infection in Rio de Janeiro State and 12 were infected in other states of Brazil. Twenty-six of 44 patients had CL, and 18 had ML. Skin ulcers in patients with CL were located on the head and neck in seven patients, upper limbs in eight, and lower limbs in 11. All patients with ML presented lesions in the nasal cavity, and in nine cases, the oral or laryngeal mucosa or both were also involved. Parasitological diagnosis was established in 37 patients. Twenty-four isolates were identified as L. (Viannia) braziliensis using multilocus isoenzyme electrophoresis. In all seven patients without parasitological confirmation, there was a strongly positive reaction to the Montenegro Skin Test using leishmanial antigens. Thirty-nine presented chronic diseases, and 29 were taking specific medication. Thirty-three of 44 patients had pretreatment alterations. The patients were given a low-dose regimen of MA, 5 mg Sb5+/kg per day, intramuscularly, in repeated series of 10 days with 10-day intervals, until progression toward lesion healing in ML and up to three series of 10 days, with 10-day intervals in CL. Clinical and laboratory examinations were performed before, during, and at the end of and 1 month after treatment to monitor toxicity, including routine serum chemistry (serum glucose, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase, urea, creatinine, amylase, and lipase), hematological examination, and electrocardiogram (EKG). Treatment was interrupted in cases of development of moderate laboratory AE or serious EKG alterations. Basal alterations that remained unchanged during treatment were excluded from the analysis of AE. During treatment, AEs (18 clinical, 22 laboratory, and 18 electrocardiographic) were observed in 31 of 44 patients (Table 1). Nine of 44 patients needed temporary interruption of MA, with regression of AEs in all cases. Complete lesion healing was obtained at the end of treatment in 33 of 44 patients. In the remaining patients, residual lesions resolved within 3 months of follow-up. Relapses in three patients were successfully retreated with MA, using the same regimen or with intralesional injection. The mean age of the Brazilian population is increasing, with a relative increase of 47.8% in the number of individuals aged 60 and older between 1997 and 2007.7 This large number of elderly patients with ATL indicates the need for alternative, less-toxic therapeutic regimens. Associated comorbidities and the concomitant use of other medications increase the frequency and severity of adverse drug reactions.8 The frequency of comorbidities and of other medication use in this study was similar to that found in elderly patients in other Brazilian studies.8, 9 Frequency and severity of the AEs observed in this elderly population were lower than those reported in other studies with MA in the general population, less vulnerable to AEs.2-6 Generally, in older adults, pharmacological treatment should be initiated with lower doses, followed by a progressive increase until achieving the desired effect or until the occurrence of toxicity.10 The results of the current study support this point of view. Studies on the pharmacokinetics of MA in elderly patients may contribute to better understanding of these clinical observations. This study showed the safety and efficacy of an intermittent low-dose MA regimen for ATL in older adults. The authors thank Sergio Salles Xavier, Andrea Silvestre de Sousa, Eleonora Carregal, Marcelus Dias da Costa, Vinícius Menezes, and Brenda Hoagland (Departamento de Doenças Infecciosas, Instituto de Pesquisa Clínica Evandro Chagas, IPEC, Fiocruz), for following up hospitalized patients; Maria Cristina Lourenço and Paulo Cezar Fialho Monteiro (Departamento de Micro-imuno-parasitologia, IPEC, Fiocruz), and Italia Mazzei Portugal and Vanja Ferreira (Departamento de Patologia e Farmacocinética, IPEC, Fiocruz) for technical support. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Sponsor's Role: This work was partially supported by Secretaria de Vigilância em Saúde, Ministério da Saúde, Brazil; Conselho Nacional de Desenvolvimento Científico e Tecnológico, Brazil, and Fundação de Amparo a Pesquisa do Estado do Rio de Janeiro, Brazil.