Introduction: The treatment of mucosal leishmaniasis (ML) is difficult due to the toxicity and route of administration of standard drugs. Miltefosine is an oral agent used for leishmaniasis treatment; however, no data exist regarding its use for ML in Brazil. In this study, we aimed to evaluate the efficacy of miltefosine for ML treatment compared to that of pentavalent antimonial in a pilot study. Methods: We performed a randomized clinical trial with two parallel groups. The tested intervention consisted of miltefosine 1.3-2 mg/kg/day (two capsules) for 28 days or intravenous 20 mg SbV/kg/day of meglumine antimoniate (N-MA) for 30 days. The final endpoint was defined as complete healing of the lesion four years after treatment. We also analyzed an early endpoint at 90 days after treatment. Results: Forty patients were included in this study: each experimental group comprised 20 patients. Applying a multivariate model in an intention-to-treat analysis, we observed that patients treated with miltefosine had a cure probability 2.08 times greater (95% confidence interval [CI] = 1.03-4.18) than those treated with N-MA at 90 days after treatment. At the final endpoint, we observed no differences in cure probability between miltefosine and N-MA (relative risk = 0.66; 95% CI = 0.33-1.32). With respect to adverse reactions, significant differences between groups were related to gastrointestinal effects, which were more frequent in the miltefosine group. Conclusions: Miltefosine may be an interesting alternative for treating ML because of its oral administration and cure rate after long-term follow-up.

Abstract:Sporotrichosis is a suba cu te or chro nic myco sis cau sed by the dimor phic fun gus Sporothrix schenc kii which is ende mic in Brazil and is trans mit ted pri ma rily through trau ma tic ino cu la tion of its causa ti ve agent into the skin. The zoo no tic trans mis sion, espe cially from infec ted cats, has been demons trated in seve ral reports and case series. We pre sent simul ta neous occur ren ce of the disea se in three members of the same family by scrat ches from an infec ted domes tic cat. Two patients deve lo ped the lympho cuta neous form and one only deve lo ped the fixed cuta neous form. Two patients were suc cess fully trea ted with satu ra ted solu tion of potas sium iodi de; howe ver, the third case repor ted side effects and had his therapy subs ti tu ted for itra co na zo le, with reso lu tion of his lesions. Keywords: Cats; Disease trans mis sion, infec tious; Potassium iodi de; Sporotrichosis Resumo: A espo ro tri co se é mico se suba gu da ou crô ni ca, cau sa da pelo fungo dimór fi co Sporothrix schenckii, endê mi ca no Brasil e trans mi ti da prin ci pal men te atra vés da ino cu la ção trau má ti ca de seu agen te cau sal na pele. A trans mis são zoo nó ti ca, espe cial men te por gatos infec ta dos, tem sido demons tra da em diver sos rela tos e séries de casos. Nós des cre ve mos a ocor rên cia simul tâ nea da doen ça em três mem bros de uma mesma famí lia atra vés da arra nha du ra por gato domés ti co infec ta do. Dois pacien tes desen vol ve ram a forma cutâ nea-lin fá ti ca e ape nas um desen vol veu a forma cutâ nea fixa. Dois pacien tes foram tra ta dos com sucesso, com solu ção satu ra da de iode to de potás sio; entre tan to, o ter cei ro caso apre sen tou efei tos cola te rais e teve seu tra ta men to subs ti tuí do por itra co na zol, com reso lu ção de suas lesões. Palavras-chave: Esporotricose; Gatos; Iodeto de potás sio; Transmissão de doen ça infec cio sa

IntroductionDiffuse cutaneous leishmaniasis (DCL) is a rare disease form associated with Leishmania (L.) amazonensis in South America. It represents the “anergic” pole of American Tegumentary Leishmaniasis, and the explanation for its resistance to treatment remains elusive. We aimed to study some possible immunological mechanisms involved in the poor DCL treatment response by evaluating some cell surface molecules obtained from a patient with DCL by flow cytometry.Case presentationA 65-year-old DCL patient who initially failed to respond to the standard treatment for the disease showed vacuolated macrophages filled with amastigotes in lesion biopsy, and L. (L.) amazonensis was identified through ITS1PCR amplification. The Leishmania skin test and indirect immunofluorescence analysis revealed negative results. Peripheral blood from the patient was collected after a few months of treatment, when the patient presented with no lesion. Peripheral blood mononuclear cells were analyzed ex vivo and in vitro after 48 h of stimulation with soluble L. (L.) amazonensis antigen (SLA). Cell death, surface molecules, and intracellular molecules, such as IFN-γ and granzyme B, were analyzed in the cells using flow cytometry. Analysis of the surface markers showed an increased expression of the inhibitory molecule programmed death ligand 1 (PD-L1) in the monocytes restimulated with SLA (approximately 65%), whereas the negative controls were 35% positive for PD-L1. Conversely, compared with the negative controls, we observed a decrease in CD4+IFN-γ+ T cells (8.32 versus 1.7%) and CD8+IFN-γ+ T cells (14% versus 1%). We also observed a relevant decrease in the granzyme B levels in the CD8+ T cells, from 31% in the negative controls to 5% after SLA restimulation.ConclusionThe dysfunctional activation of PD-L1 inhibitory pathway after Leishmania antigen stimulation and reduced levels of IFN-gamma and granzyme B-producing cells could be closely related to unresponssiveness to standard drug treatment of DCL patient.

American cutaneous leishmaniasis, an endemic and increasing disease in Brazil, can present as skin ulcers and lesions in the mucous membranes of the nose, mouth and pharynx. Pentavalent antimony is the first choice drug for treatment, with a less favorable response of the mucosal forms. The difficulty of diagnosing and treating a case of mucosal leishmaniasis in a five-year-old child, with negative parasitological and immunological tests and polymerase chain reaction is emphasized. Only after several attempts was the smear test positive. The patient developed persistent secondary bacterial infection on the lesions, lack of response to specific drugs and antibiotics and evoluted to septicemia and death.

5 Kono M, Nomura T, Ohguchi Y et al. Comprehensive screening for a complete set of Japanese-population-specific filaggrin gene mutations. Allergy 2014; 69: 537-540. 6 Gruber R, Janecke AR, Grabher D, Sandilands A, Fauth C, Schmuth M. Evidence for genetic modifiers other than filaggrin mutations in X-linked ichthyosis. J Dermatol Sci 2010; 58: 72-82. 7 Uehara M, Hayashi S. Hyperlinear palms: association with ichthyosis and atopic dermatitis. Arch Dermatol 1981; 117: 490-491. 8 Cuevas-Covarrubias SA, Vald es-Flores M, Orozco Orozco E, D ıaz-Zagoya JC, Kofman-Alfaro SH. Are atopy and palm-sole hyperlinearity clinical tools in the differential diagnosis between ichthyosis vulgaris and X-linked ichthyosis?.

IntroductionAmerican tegumentary leishmaniasis (ATL), which can present as either cutaneous (CL) or mucosal leishmaniasis (ML), is endemic in South America, and first-line antimonial treatments are known for their wide range of adverse effects (AEs). Growing reports of drug resistance increase the urgency of the need for better treatment options. The objective of this pilot clinical trial was to assess the efficacy of and AEs associated with the oral combination of miltefosine and pentoxifylline based on a post hoc analysis.MethodsA pilot, randomized, open-label clinical trial was performed. The experimental group (M+P) received 50 mg twice a day (BID) miltefosine and 400 mg three times a day (TID) pentoxifylline, and the control group (A+P) received 20 mg Sb+V/kg/day intravenously and 400 mg TID pentoxifylline. Patients with ML received treatment for 28 days, and patients with CL received treatment for 20 days.ResultsForty-three patients were included: 25 with ML and 18 with CL caused by L.(V.) braziliensis. AEs were more frequent in the A+P group (p=0.322), and there was a need for treatment interruption due to severe AEs (p=0.027). Patients with CL had a higher chance of achieving a cure (p=0.042) and a higher risk of AEs (p=0.033). There was no difference in the chance of a cure based on the treatment (p=0.058).ConclusionIn this pilot randomized clinical trial, M+P treatment and A+P treatment yielded similar cure rates, and the former was associated with a lower risk of AEs. Future studies with more patients and longer follow-up are recommended.

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Abstract:The vast majority of cases of cutaneous leishmaniasis are represented by limb injuries. A female patient, white, presented an ulcer with infiltrated borders located on the fourth finger of the left hand following occupational exposure in an area of native forest. Diagnosis of cutaneous leishmaniasis caused by Leishmania of the subgenus Viannia was confirmed. The patient failed to respond to treatment with antimony, but achieved clinical cure after this was associated with pentoxifylline. The case highlights the rarity of the periungual location of the leishmanial lesion and the difficulties encountered in therapy. Keywords: Diagnosis; Leishmania braziliensis; Leishmaniasis, mucocutaneous; Polymerase chain reaction Resumo: A grande maioria dos casos de leishmaniose tegumentar é representada por lesões nos membros. Paciente feminina, branca, diabética, apresentou úlcera com bordas infiltradas, localizada no quarto quirodáctilo esquerdo, após exposição ocupacional em área de mata nativa. Foi confirmado o diagnóstico de leishmaniose tegumentar por Leishmania do subgênero Viannia. Não respondeu ao tratamento com antimonial, mas obteve cura clínica após associação com a pentoxifilina. O caso destaca-se pela raridade da localização periungueal da lesão leishmaniótica e pela dificuldade terapêutica. Palavras-chave: Diagnóstico; Leishmania braziliensis; Leishmaniose mucocutânea; Reação em cadeia da polimerase