Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for Cutaneous Leishmaniasis

Brito, Graça; Dourado, Mayra; Guimarães, Luiz Henrique; Meireles, Everson; Schriefer, Albert; Carvalho, Edgar M.; Machado, Paulo Roberto Lima

doi:10.4269/ajtmh.16-0435

Cited by 33 publications

(27 citation statements)

References 12 publications

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“…Those studies have shown that the combination of Sb v with PTX led to the healing of lesions of refractory cases of ML, as well as a higher cure rate when compared with Sb v and placebo in a controlled randomized trial. 12,15,16,19 This was also observed here. Although the time of healing varied in the To better understand the mechanisms that led to this successful treatment, we evaluated the cellular composition of lesions from patients treated with Sb v alone and with the combination of PTX with Sb v , as well as cytokine and granzyme A expression, which are involved in immunoregulation and cytotoxic activity, respectively.…”

Section: Discussionsupporting

confidence: 88%

In Situ Cellular Response Underlying Successful Treatment of Mucosal Leishmaniasis with a Combination of Pentavalent Antimonial and Pentoxifylline

Faria

Barbieri

Koh

et al. 2019

The American Journal of Tropical Medicine and Hygiene

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Mucosal leishmaniasis (ML) is characterized by high production of inflammatory cytokines. Administration of pentoxifylline (PTX), an inhibitor of TNF-alpha, with pentavalent antimony (Sb v), has been successfully used as alternative treatment for refractory ML. Our study aims to investigate the in situ cellular response underlying the effectiveness of this therapy, by evaluating the intensity of the inflammatory infiltrate, cellular composition, and expression of cytokines and granzyme A in lesions from ML before and after treatment with Sb v alone or in combination with PTX. Our data showed no differences in the intensity of inflammatory infiltrate comparing before and after treatment, and comparing between different treatments. However, although the number and frequency of CD4 + and CD8 + cells were not different before and after treatments or comparing different treatments, frequency of CD68 + cells decreased after treatment with Sb v + PTX, but not with Sb v. This was due to a reduction in CD68 + TNF-alpha + and not in CD68 + IL-10 + cells. The frequency of TNFalpha + cells was correlated with the intensity of the inflammatory infiltrate before treatment, but this correlation was lost after treatment with Sb v + PTX. Although the total expression of granzyme A did not significantly change after treatments, a clear trend of decrease was observed after treatment with Sb v + PTX. Interestingly, patients who took longer to heal, regardless of the treatment, displayed a higher frequency of granzyme A + cells. Our data suggest that treatment with Sb v + PTX acts in CD68 + cells reducing the expression of TNF-alpha but not IL-10, resulting in more efficient modulation of the inflammatory response, accelerating the healing process.

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Section: Discussionsupporting

confidence: 88%

In Situ Cellular Response Underlying Successful Treatment of Mucosal Leishmaniasis with a Combination of Pentavalent Antimonial and Pentoxifylline

Faria

Barbieri

Koh

et al. 2019

The American Journal of Tropical Medicine and Hygiene

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“…The meglumine antimoniate associated with pentoxifylline (Machado et al 2007) were classified as clinically useful and with acceptable risk with specialized monitoring (Machado et al 2007 [15]). On the other hand the combination of meglumine antimoniate associated with pentoxifylline performed by Brito et al 2017 [31] to treat cutaneous leishmaniasis caused by Leishmania braziliensis was classified as not efficacious and not useful. Meglumine antimoniate associated with omeprazole (Nilforoushzadeh et al 2008 [26]) was classified as clinically useful and with acceptable risk with specialized monitoring.…”

Section: Resultsmentioning

confidence: 99%

Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review

Berbert

Mello

Nassif

et al. 2018

Dermatology Research and Practice

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The first choice drugs for the treatment of cutaneous and mucocutaneous leishmaniasis are pentavalent antimonials, sodium stibogluconate, or meglumine antimoniate. However, the treatment with these drugs is expensive, can cause serious adverse effects, and is not always effective. The combination of two drugs by different routes or the combination of an alternative therapy with systemic therapy can increase the efficacy and decrease the collateral effects caused by the reference drugs. In this systematic review we investigated publications that described a combination of nonconventional treatment for cutaneous and mucocutaneous with pentavalent antimonials. A literature review was performed in the databases Web of Knowledge and PubMed in the period from 01st of December 2004 to 01st of June 2017, according to Prisma statement. Only clinical trials involving the treatment for cutaneous or mucocutaneous leishmaniasis, in English, and with available abstract were added. Other types of publications, such as reviews, case reports, comments to the editor, letters, interviews, guidelines, and errata, were excluded. Sixteen articles were selected and the pentavalent antimonials were administered in combination with pentoxifylline, granulocyte macrophage colony-stimulating factor, imiquimod, intralesional sodium stibogluconate, ketoconazole, silver-containing polyester dressing, lyophilized LEISH-F1 protein, cryotherapy, topical honey, and omeprazole. In general, the combined therapy resulted in high rates of clinical cure and when relapse or recurrence was reported, it was higher in the groups treated with pentavalent antimonials alone. The majority of the articles included in this review showed that cure rate ranged from 70 to 100% in patients treated with the combinations. Serious adverse effects were not observed in patients treated with drugs combination. The combination of other drugs or treatment modalities with pentavalent antimonials has proved to be effective for cutaneous and mucocutaneous leishmaniasis and for most seemed to be safe. However, new randomized, controlled, and multicentric clinical trials with more robust samples should be performed, especially the combination with immunomodulators.

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“…4,15 Other studies also indicate that in CL patients with severe lesions caused by Leishmania braziliensis, anti-TNF treatment can help the healing process and enhance ulcer cicatrization, 16 although no consensus has been established. 17 In the present case, it is difficult to determine whether the severity of the CL symptoms was due to the concomitant disease, the administration of anti-TNF drugs or cortisone, or a combination of factors.…”

Section: Discussionmentioning

confidence: 72%

Case Report: Diffuse Cutaneous Leishmaniasis by Leishmania infantum in a Patient Undergoing Immunosuppressive Therapy: Risk Status in an Endemic Mediterranean Area

Alcover

Rocamora

Guillén

et al. 2018

The American Journal of Tropical Medicine and Hygiene

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This case report highlights the risk of severe cutaneous leishmaniasis (CL) by in patients undergoing immunosuppressant therapy who either live in an endemic area or are visiting in the transmission season. The case patient, resident in Majorca (Balearic Islands), presented 12 disseminated erythematous skin lesions, 1-6 cm in diameter, located on the scalp, cheek, umbilical region, and lower extremities 8 years after undergoing anti-tumor necrosis factor (TNF) therapy. Parasite presence in peripheral blood and high levels of specific antibodies were also observed, indicating a possible risk of CL shifting toward a visceral infection. However, once CL was diagnosed, anti-TNF therapy was discontinued and liposomal amphotericin B was administered, resulting in a complete healing of lesions, no DNA detection in blood, and an important serological decrease in antibodies. The lack of data on the supposed epidemiological association between leishmaniasis and immunosuppressive therapy highlights the importance of implementing surveillance systems in endemic areas. No obvious relationship was found based on the data provided by the Balearic Islands Epidemiological System, in contrast with data reported in nearby endemic areas. This indicates that if the suspected association is to be clarified, greater efforts are needed to report information about concomitant diseases and therapies in leishmaniasis patients.

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Oral Pentoxifylline Associated with Pentavalent Antimony: A Randomized Trial for Cutaneous Leishmaniasis

Cited by 33 publications

References 12 publications

In Situ Cellular Response Underlying Successful Treatment of Mucosal Leishmaniasis with a Combination of Pentavalent Antimonial and Pentoxifylline

In Situ Cellular Response Underlying Successful Treatment of Mucosal Leishmaniasis with a Combination of Pentavalent Antimonial and Pentoxifylline

Pentavalent Antimonials Combined with Other Therapeutic Alternatives for the Treatment of Cutaneous and Mucocutaneous Leishmaniasis: A Systematic Review

Case Report: Diffuse Cutaneous Leishmaniasis by Leishmania infantum in a Patient Undergoing Immunosuppressive Therapy: Risk Status in an Endemic Mediterranean Area

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