Seventeen years of American cutaneous leishmaniasis in a Southern Brazilian municipality

We reviewed the records of 151 patients diagnosed with American cutaneous leishmaniasis (ACL) from 1993 to 2009 in the municipality of Japura, Paraná, Brazil. Gender, age, occupation, place of residence, location of lesions, type and number of lesions were analyzed. The prevalence rate of ACL was 11.5/10,000 hab, of which 84.7% were male, 58.3% lived in rural area and 49.0% were farmers. The most frequent age group was between 30 to 39 years (26.6%). Skin lesions occurred in 92.7% of the patients with predominance in the lower limbs (23.9%) and 49.1% of the records did not include the number of lesions location due to incomplete filling. A single ulceration was present in 44.4%. Japurá is an endemic area for ACL, requiring public actions and preventive education.

Thermoterapy effective and safer than miltefosine in the treatment of cutaneous leishmaniasis in Colombia

In Colombia, pentavalent antimonials and miltefosine are the drugs of choice for the treatment of cutaneous leishmaniasis; however, their toxicity, treatment duration, (treatment adherence problems), cost, and decreased parasite sensitivity make the search for alternative treatments of American cutaneous leishmaniasis necessary. Based on the results found in a controlled, open, randomized, phase III clinical trial, the efficacy and safety of miltefosine was compared to that of thermotherapy for the treatment of cutaneous leishmaniasis in Colombia. Adult patients from the Colombian army participated in the study; they received either 50 mg of miltefosine three times per day for 28 days by the oral route (n = 145) or a thermotherapy (Thermomed®) application of 50 °C for 30 seconds over the lesion and surrounding area (n = 149). Both groups were comparable with respect to their sociodemographic, clinical, and parasitological characteristics. The efficacy of miltefosine by protocol and by intention to treat was 70% (85/122 patients) and 69% (85/145 patients), respectively. The adverse effects were primarily gastrointestinal for miltefosine and pain at the lesion site after treatment for thermotherapy. No statistically significant difference was found in the efficacy analysis (intention to treat and protocol) between the two treatments. ClinicalTrials.gov: NCT00471705.

Long-Term Evaluation of Recurrence after Photodynamic Therapy with Topical Methyl Aminolevulinate for Non-Melanoma Skin Cancer: a Hospital-Based Study

Introduction & Objectives: Several factors may influence the decision to pursue nonsurgical modalities for the treatment of non-melanoma skin cancer. Topical photodynamic therapy (PDT) is a non-invasive alternative treatment reported to have a high efficacy when using standardized protocols in Bowen’s disease (BD), superficial basal cell carcinoma (BCC) and in thin nodular BCC. However, long-term recurrence studies are lacking. The aim of this study was to evaluate the long-term efficacy of PDT with topical methylaminolevulinate (MAL) for the treatment of BD and BCC in a dermato-oncology department. Materials & Methods: All patients with the diagnosis of BD or BCC, treated with MAL-PDT from the years 2004 to 2008, were enrolled. Treatment protocol included two MAL-PDT sessions one week apart repeated at three months when incomplete response, using a red light dose of 37-40 J/cm2 and an exposure time of 8’20’’. Clinical records were retrospectively reviewed, and data regarding age, sex, tumour location, size, treatment outcomes and recurrence were registered. Descriptive analysis was performed using chi square tests, followed by survival analysis with the Kaplan-Meier and Cox regression models. Results: Sixty-eight patients (median age 71.0 years, P25;P75=30;92) with a total of 78 tumours (31 BD, 45 superficial BCC, 2 nodular BCC) and a median tumour size of 5 cm2 were treated. Overall, the median follow-up period was 43.5 months (P25;P75=0;100), and a total recurrence rate of 33.8% was observed (24.4 % for BCC vs. 45.2% for BD). Estimated recurrence rates for BCC and BD were 5.0% vs. 7.4% at 6 months, 23.4% vs. 27.9% at 12 months, and 30.0% vs. 72.4% at 60 months. Both age and diagnosis were independent prognostic factors for recurrence, with significantly higher estimated recurrence rates in patients with BD (p=0.0036) or younger than 58 years old (p=0.039). The risk of recurrence (hazard ratio) was 2.4 times higher in patients with BD compared to superficial BCC (95% CI:1.1-5.3; p=0.033), and 2.8 times higher in patients younger than 58 years old (95% CI:1.2-6.5; p=0.02). Conclusions: In the studied population, estimated recurrence rates are higher than those expected from available literature, possibly due to a longer follow-up period. To the authors’ knowledge there is only one other study with a similar follow-up period, regarding BCC solely. BD, as an in situ squamous cell carcinoma, has a higher tendency to recur than superficial BCC. Despite greater cosmesis, PDT might no be the best treatment option for young patients considering their higher risk of recurrence.

Melanoma da íris em idade pediátrica

Apresentado como poster no 57º Congresso Português de Oftalmologia, Algarve, Portugal, Dezembro de 2014

Recidiva de Cancro Cutâneo Não-Melanoma após Terapêutica Fotodinâmica num Serviço de Dermatologia

Introdução: São escassos os estudos de eficácia a longo prazo da terapêutica fotodinâmica(TFD) no tratamento da doença de Bowen (DB) e do carcinoma basocelular (CBC). Objectivos: Determinar a eficácia a longo prazo da TFD com metilaminolevulinato (MAL) no tratamento da DB e do CBC pela análise de recidiva. Material e método: Foram analisados retrospectivamente os processos clínicos de doentes com o diagnóstico de DB ou CBC tratados com TFD-MAL num serviço de Dermato- Oncologia entre 2004 e 2008. Foi efectuada a análise descritiva dos dados pelo teste do chiquadrado, seguida da análise de sobrevivência pelos métodos de Kaplan-Meier e regressão de Cox. Resultados: Foram tratados 68 doentes (mediana etária 71 anos, P25;P75=30;92) com um total de 78 tumores (31 DB, 45 CBC superficiais, 2 CBC nodulares finos). No período de seguimento efectuado (mediana 43,5 meses, P25;P75=0;100) observou-se uma taxa de recidiva de 25% no CBC e 45,2% na DB. As taxas de recidiva estimadas para os CBC e DB foram de 5,0% vs. 7,4% aos 6 meses, 23,4% vs. 27,9% aos 12 meses e de 30,0% vs. 72,4% aos 60 meses. Idade e diagnóstico constituíram factores independentes de prognóstico, com taxas de recidiva significativamente maiores nos doentes com DB (p=0,0036) ou com menos de 58 anos (p=0,039). De modo semelhante, o risco de recidiva foi 2,4 vezes superior nos doentes com DB face àqueles com CBC (p=0,033) e 2,8 vezes maior em doentes com menos de 58 anos (p=0,02). Conclusões: Na população estudada, a taxa de recidiva foi superior àquela encontrada na literatura. A TFD pode não ser a melhor opção para o tratamento do cancro cutâneo nãomelanoma em doentes mais jovens, em particular na doença de Bowen. Apesar do melhor resultado cosmético, o risco de recidiva deve ser equacionado e a escolha terapêutica deve ser ponderada caso a caso.

ASPECTS OF THE ECOLOGY OF PHLEBOTOMINES (Diptera: Psychodidae: Phlebotominae) IN AN AREA OF CUTANEOUS LEISHMANIASIS OCCURRENCE, MUNICIPALITY OF ANGRA DOS REIS, COAST OF RIO DE JANEIRO STATE, BRAZIL

Over a complete two-year period, phlebotomine specimens were caught in an area of cutaneous leishmaniasis occurrence in the municipality of Angra dos Reis. A manual suction tube was used to catch phlebotomines on house walls, and also light traps in domestic and peridomestic settings and in the forest. This yielded 14,170 specimens of 13 species: two in the genus Brumptomyia and eleven in the genus Lutzomyia. L. intermedia predominantly in domestic and peridomestic settings, with little presence in the forest, with the same trend being found in relation to L. migonei, thus proving that these species have adapted to the human environment. L. fischeri appeared to be eclectic regarding location, but was seen to be proportionally more endophilic. L. intermedia and L. migonei were more numerous in peridomestic settings, throughout the year, while L. fischeri was more numerous in domestic settings except in March, April, May and September. From the prevalence of L. intermedia, its proven anthropophily and findings of this species naturally infected with Leishmania(Viannia) braziliensis, it can be incriminated as the main vector for this agent of cutaneous leishmaniasis in the study area, especially in the peridomestic environment. L. fischeri may be a coadjuvant in carrying the parasite.

Carcinoma Oculto da Mama com Metástases Axilares. A Propósito de Dois Casos Clínicos

INTRODUÇÃO: O carcinoma oculto é uma entidade pouco frequente, que se define como a presença de metástases com tumor primário indetetável na altura da apresentação. O prognóstico da maioria dos casos de tumor oculto é reservado, no entanto, o desenvolvimento de técnicas imunohistoquímicas que permitem a caracterização do tumor, tornaram alguns subgrupos de tumor oculto potencialmente curáveis. A presença de adenopatias axilares é a forma de apresentação do cancro da mama em 0,3-1% das mulheres, sendo a origem mais provável a mama ipsilateral. CASO CLÍNICO: Os autores relatam dois casos clínicos de tumor oculto da mama: Caso 1: Doente de 57 anos, com antecedentes familiares de primeiro e segundo grau de cancro da mama, com estudo genético negativo. Recorreu à consulta por adenopatia axilar direita.Exame objetivo (EO), mamografia + ecografia mamária normais. Microbiópsia (MB) ganglionar:metástase de carcinoma compatível com origem na mama, recetores de estrogénios (RE) +, HER2 +, CK7 +, Ca125 +, CK20 (-). RMN mamária e PET não identificaram tumor primário. Procedeu-se a dissecção axilar: 10 gânglios sem metástases. Realizou terapêutica adjuvante com quimioterapia (QT) e imunoterapia (IT). Manteve follow-up regular com EO, RMN e mamografia alternadas até aos 4 anos sem alterações. Aos 4,5 anos detetou-se ao E.O. nódulo palpável na mama direita e nódulo axilar. Mamografia + ecografia: lesão sólida suspeita (R5) cuja caracterização histológicademonstrouCDIG3, recetores hormonais (-) (RH), HER2 3+, Ki67 >30%. A TC TAP e a cintigrafia óssea não revelaram alterações. Em reunião multidisciplinar de decisão terapêutica (RMDT) decidiu-serealizar mastectomia total direita + mastectomia profilática contralateral com reconstrução. Exame histológico:CDI G3 com 22mm,confirmando-se a caracterização imunohistoquímica, com invasão vascular e presença de 3 gânglios com metástase e extensão extracapsular (T2 N2). Realizou terapêutica adjuvante com QT + IT+ Radioterapia (RT) da parede torácica e ganglionar. Um ano após a mastectomia, a doente mantém-se em follow-up sem sinais de recidiva. Caso 2: Doente de 50 anos, com antecedentes familiares de primeiro grau de cancro da mama. Recorreu à consulta por nódulo da axila esquerda e nódulo da mama direita com 2 meses de evolução. EO: nódulo palpável da mama direita e duas adenopatias axilares à esquerda. Mamografia + eco: microcalcificações atípicas da mama esquerda (R5) ealterações benignas da mama direita (R2). Realizaram-se microbiópsia por estereotaxia e biópsia assistida por vácuo da mama esquerda e citologia aspirativa de agulha fina (CAAF) de nódulo da mama direita:sem alterações neoplásicas. A biópsia de adenopatia axilar revelou metástase ganglionar de carcinoma compatível com origem na mama, RH (-), GCDFP15 (-),HER2 3+ e CK7 +.A RM mamária revelou apenas lesões benignas. TC TAP, ecografia abdominal e cintigrafia óssea normais. PET: lesão localizada na axila esquerda, nos três níveis axilares. Por recusa da doente em realizar microbiópsias adicionais ou mastectomia radical modificada, optou-se por realizar dissecção axilar esquerda. Exame histológico: 7 em 14 gânglios com metástases, morfologia e estudo imunohistoquímico concordantes com o anterior. Em RMDT foi decidida terapêuticaadjuvante com RT, QT e IT que a doente se encontra no momento a realizar. DIAGNÓSTICOS DIFERENCIAIS/ DISCUSSÃO A presença de adenopatias axilares relaciona-se na maioria dos casos com processos benignos, mas naqueles em que se diagnostica uma neoplasia maligna, mais de 50% correspondem a carcinoma da mama. Outras neoplasias que se podem apresentar com metástases axilares são: linfoma, melanoma, sarcoma, tiróide, pulmão, estômago, ovário, útero. A avaliação diagnóstica deve incluir além do exame físico, a biópsia ganglionar (para exame histológico e caracterização imunohistoquímica), mamografia, ecografia mamária e ressonância magnética mamária, eventual TC toraco-abdominal, cintigrafia óssea nas mulheres sintomáticas, existindo controvérsia sobre autilidade da PET. CONCLUSÕES O tumor oculto representa um problema diagnóstico e um desafio terapêutico. O carcinoma da mama apresentando-se sob a forma de metástase axilar sem tumor primário identificável e sem doença à distância, considera-se um dos casos potencialmente curáveis, se for tratado de acordo com as guidelines para o estadio II do cancro da mama. A abordagem recomendada inclui dissecção axilar, de importância crucial pela informação prognóstica que guiará o restante tratamento e por ajudar no controlo local da doença. A terapêutica adequada da mama ipsilateral é controversa, e pode passar pela mastectomia radical modificada ou RT. Não existem até à data estudos randomizados comparando a mastectomia versus RT mamária e os estudos retrospetivos disponíveis não apresentam resultados consensuais. A decisão de RT da parede torácica pós-mastectomia e de terapêutica adjuvante deverá ser tomada tendo em conta as guidelines publicadas. BIBLIOGRAFIA 1- www.uptodate.com; Kaklamani, V., et al; “Axillary node metastases with occult primary breast cancer”; Mar 2012 2- Wang, J., et al; “Occult breast cancer presenting as metastatic adenocarcinoma of unknown primary: clinical presentation, immunohistochemistry, and molecular analysis”; Case Rep Oncol 2012;5:9-16 3- Takabatake, D.; “Two cases of occult breast cancer in which PET-CT was helpful in identifying primary tumors”; Breast Cancer (2008) 15:181-184 4- Kinoshita, S., et al.; “Metachronous secondary primary occult breast cancer initially presenting with metastases to the contralateral axillary lymph nodes: report of a case”; Breast Cancer (2010) 17:71-74 5- Bresser, J., et al; “Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review”; EJSO 36 (2010) 114-119 6- Sharon, W., et al.; “Benefit of ultrasonography in the detection of clinically and mammographically occult breast cancer”; World J Surg (2008) 32:2593-2598 7- Masinghe, S.P., et al.; “Breast radiotherapy for occult breast cancer with axillary nodal metastases – does it reduce the local recurrence rate and increase overall survival?”; Clinical Oncology 23 (2011) 95-100 8- Altan, E., et al.; “Clinical and pathological characteristics of occult breast cancer and review of the literature”; J Buon 2011 Jul-Sep;16(3):434-6

FACTORS ASSOCIATED TO ADHERENCE TO DIFFERENT TREATMENT SCHEMES WITH MEGLUMINE ANTIMONIATE IN A CLINICAL TRIAL FOR CUTANEOUS LEISHMANIASIS

The favorable outcome of the treatment of a disease is influenced by the adherence to therapy. Our objective was to assess factors associated with adherence to treatment of patients included in a clinical trial of equivalence between the standard and alternative treatment schemes with meglumine antimoniate (MA) in the treatment of cutaneous leishmaniasis (CL), in the state of Rio de Janeiro. Between 2008 and 2011, 57 patients with CL were interviewed using a questionnaire to collect socioeconomic data. The following methods were used for adherence monitoring: counting of vial surplus, monitoring card, Morisky test and modified Morisky test (without the question regarding the schedule); we observed 82.1% (vial return), 86.0% (monitoring card), 66.7% (Morisky test) and 86.0% (modified Morisky test) adherence. There was a strong correlation between the method of vial counting and the monitoring card and modified Morisky test. A significant association was observed between greater adherence to treatment and low dose of MA, as well as with a lower number of people sleeping in the same room. We recommend the use of the modified Morisky test to assess adherence to treatment of CL with MA, because it is a simple method and with a good performance, when compared to other methods.

MOLECULAR DETECTION OF Leishmania IN PHLEBOTOMINE SAND FLIES IN A CUTANEOUS AND VISCERAL LEISHMANIASIS ENDEMIC AREA IN NORTHEASTERN BRAZIL

Several phlebotomine sand fly species have been regarded as putative or proven vectors of parasites of the genus Leishmania in Brazil, but data for the northeastern region remains incipient. In this study, a total of 600 phlebotomine sand flies were grouped in pools of 10 specimens each and tested by a Leishmania genus-specific PCR and by a PCR targeting Leishmania (Leishmania) infantum. Fourteen out of 60 pools were positive by the genus-specific PCR, being five pools of L. migonei, seven of L. complexa, one of L. sordellii and one of L. naftalekatzi, which correspond to a minimal infection rate of 2.3% (14/600). Our results, associated with their known anthropophily and their abundance, suggest the participation of L. migonei and L. complexa as vectors of Leishmania in northeastern Brazil. Remarkably, this is the first time in this country that the detection of Leishmania DNA in L. sordellii and L. naftalekatzi has been reported, but future studies are necessary to better understand the significance of these findings.

RESOLUTION OF CUTANEOUS LEISHMANIASIS AFTER ACUTE ECZEMA DUE TO INTRALESIONAL MEGLUMINE ANTIMONIATE

We report a case of a 42 year-old female, who came to a leishmaniasis reference center in Rio de Janeiro, Brazil, presenting a cutaneous leishmaniasis lesion in the right forearm. Treatment with low-dose intramuscular meglumine antimoniate (MA) (5 mg Sb5+/kg/day) was initiated, with improvement after 28 days, although with the development of generalized eczema. After 87 days, the lesion worsened. Patient refused treatment with amphotericin B. MA was then infiltrated in the lesion, in two sessions, resulting in local eczema, with bullae formation; however, twenty days after, both the ulcer and eczema receded. Intralesional administration of MA should be used carefully when previous cutaneous hypersensitivity is detected.

MONTENEGRO SKIN TEST AND AGE OF SKIN LESION AS PREDICTORS OF TREATMENT FAILURE IN CUTANEOUS LEISHMANIASIS

A case-control study was conducted to examine the association among the Montenegro skin test (MST), age of skin lesion and therapeutic response in patients with cutaneous leishmaniasis (CL) treated at Evandro Chagas National Institute of Infectious Diseases (INI), Oswaldo Cruz Foundation (FIOCRUZ), Rio de Janeiro, Brazil. For each treatment failure (case), two controls showing skin lesion healing following treatment, paired by sex and age, were randomly selected. All patients were treated with 5 mg Sb5+/kg/day of intramuscular meglumine antimoniate (Sb5+) for 30 successive days. Patients with CL were approximately five times more likely to fail when lesions were less than two months old at the first appointment. Patients with treatment failure showed less intense MST reactions than patients progressing to clinical cure. For each 10 mm of increase in MST response, there was a 26% reduction in the chance of treatment failure. An early treatment - defined as a treatment applied for skin lesions, which starts when they are less than two months old at the first appointment -, as well as a poor cellular immune response, reflected by lower reactivity in MST, were associated with treatment failure in cutaneous leishmaniasis.

GENOTYPE CHARACTERIZATION OF Leishmania (Viannia) braziliensis ISOLATED FROM HUMAN AND CANINE BIOPSIES WITH AMERICAN CUTANEOUS LEISHMANIASIS

Introduction:American tegumentary leishmaniasis (ATL) can be caused by Leishmania (Viannia) braziliensis complex. The evolution of ATL initially results in lesions and can develop into disseminated or diffuse forms. The genetic diversity of L. (V.) braziliensis in some endemic areas of Brazil has been poorly studied, such as in the state of São Paulo. This study analyzed the genetic diversity of L. (V.) braziliensis isolates collected from patients and dogs with LTA from the state of São Paulo.Methods:Leishmaniasis diagnosis was determined by PCR. The 132 biopsies were collected in different regions of Sao Paulo State, Brazil (36 municipalities). The genetic characterization of L. (V.) braziliensis isolates was tested by RFLP-PCR using DNA extracted from biopsies. The primer set amplified a specific region of Leishmania internal transcribed spacers of the ribosomal DNA locus.Results:Of the 132 samples, 52 (40%) were completely genotyped by RFLP-PCR (44 from human patients and eight from dogs). The results showed nine distinct patterns. The majority of the genotyped samples were from Sorocaba (30), and the others were distributed among 14 other municipalities. The first pattern was more frequent (29 samples), followed by pattern 2 (nine samples) and pattern 3 (three samples). Patterns 4, 6, 7, 8 and 9 were composed of two samples each and pattern 5 of one sample.Conclusion:These results suggest that polymorphic strains of L. (V.) braziliensis circulate in the state of São Paulo. These data agree with studies from other regions of Brazil, showing great variability among the natural populations of endemic foci.

MOLECULAR CHARACTERIZATION OF AMERICAN CUTANEOUS LEISHMANIASIS IN THE TRI‑BORDER AREA OF ASSIS BRASIL, ACRE STATE, BRAZIL

SUMMARY In this study, Leishmaniaspecies were identified by Polymerase Chain Reaction (PCR). The epidemiology of patients suspected of having American Cutaneous Leishmaniasis in the municipality of Assis Brasil, Acre State, located in the Brazil/Peru/Bolivia triborder was also investigated. By PCR, the DNA of Leishmaniawas detected in 100% of the cases (37 samples) and a PCR-Restriction Fragment Length Polymorphism (RFLP) of the hsp 70gene identified the species in 32 samples: Leishmania (Viannia) braziliensis (65.6%) , L. (V.) shawi (28.1%) , L. (V.) guyanensis (3.1%) and mixed infection L. (V.) guyanensis and L. (Leishmania) amazonensis (3.1%)This is the first report of L. (V.) shawiand L. (L.) amazonensis in Acre. The two predominant species were found in patients living in urban and rural areas. Most cases were found in males living in rural areas for at least three years and involved in rural work. This suggests, in most cases, a possible transmission of the disease from a rural/forest source, although some patients had not engaged in activities associated with permanence in forestall areas, which indicate a possible sandflies adaptation to the periurban setting.

FIRST REPORT OF CUTANEOUS LEISHMANIASIS CAUSED BY Leishmania (Leishmania) infantum chagasi IN AN URBAN AREA OF RIO DE JANEIRO, BRAZIL

SUMMARY American tegumentary leishmaniasis (ATL) is an infectious disease caused by protozoa of the genus Leishmania, and transmitted by sandflies. In the state of Rio de Janeiro, almost all of the cases of American tegumentary leishmaniasis (ATL) are caused by Leishmania (Viannia) braziliensis, while cases of visceral leishmaniasis (VL) are caused by Leishmania (Leishmania) infantum chagasi. The resurgence of autochthonous VL cases in Rio de Janeiro is related to the geographic expansion of the vector Lutzomyia longipalpis and its ability to adapt to urban areas. We report the first case of leishmaniasis with exclusively cutaneous manifestations caused by L. (L.) infantum chagasi in an urban area of Rio de Janeiro. An eighty-one-year-old woman presented three pleomorphic skin lesions that were not associated with systemic symptoms or visceromegalies. Multilocus enzyme electrophoresis identified L. (L.) infantum chagasi, but direct smear and PCR of bone narrow were negative for Leishmania sp. (suggesting exclusively cutaneous involvement). We discuss the different dermatological presentations of viscerotropic leishmaniasis of the New and Old World, and the clinical and epidemiological importance of the case. Etiologic diagnosis of ATL based upon exclusive clinical criteria may lead to incorrect conclusions. We should be aware of the constant changes in epidemiological patterns related to leishmaniases.

Exacerbation of Recalcitrant Cutaneous Sarcoidosis with Adalimumab - a Paradoxical Effect? A Case Report

The paradoxical adverse effects of tumor necrosis factor-alpha (TNF-alpha) antagonists have been described frequently as a result of the widespread use of these drugs. Among the TNF-alpha blocking agents, few reports exist relating the use of adalimumab in cutaneous sarcoidosis, although all of them show good results. More recently, sarcoidosis onsets have been reported with various TNF-alpha inhibitors. The current case is, to our knowledge, the first to describe the exacerbation of cutaneous lesions of sarcoidosis treated with adalimumab.