Fenómeno de Lucio como forma de presentación de enfermedad de Hansen / Lucio's phenomenon as a presentation of Hansen disease / Fenômeno de Lucio como forma de apresentação da hanseníase

Resumen: Introducción: la enfermedad de Hansen es una enfermedad infecciosa crónica, causada por Mycobacterium leprae, que afecta principalmente piel y nervios periféricos. Las reacciones leprosas son eventos agudos que se asocian a un aumento de la morbimortalidad de la enfermedad. Objetivo: presentar el caso clínico de un paciente con fenómeno de Lucio, a través del cual se llegó al diagnóstico de enfermedad de Hansen, y remarcar la importancia de tener presente esta enfermedad, poco frecuente en nuestro país, para su correcto diagnóstico. Discusión: el fenómeno de Lucio es un tipo de reacción leprosa mediada por inmunocomplejos. Se caracteriza clínicamente por máculas o placas eritematovioláceas, de aparición súbita, que evolucionan a úlceras necróticas y curan dejando cicatrices estrelladas atróficas. De no mediar tratamiento, puede ser fatal, debido a sobreinfección y sepsis. Este se basa en el tratamiento específico de la infección, asociado a prednisona y un correcto manejo de las heridas.

Summary: Introduction: Hansen disease is a chronic infectious disease caused by Mycobacterium leprae, which mainly affects the skin and peripheral nerves. Leprosy reactions are acute events associated to an increase in the morbimortality of the disease. Objective: the study aims to present the clinical case of patient with Lucio´s phenomenon, which allowed the diagnosis of Hansen disease, and to emphasize on the importance of having this disease in mind for an appropriate diagnosis, despite it being rather unusual in our country. Discussion: Lucio´s phenomenon is a kind of leprosy reaction mediated by immune complexes. Clinically, it is characterized by the sudden onset of macules or blue hemorrhagic plaques, with a rapid evolution to necrotic ulcers, and it heals leaving star-shaped atrophic scars. If it is not treated, it may be fatal due to superinfection and sepsis. Treatment is based on specific medication for the infection, associated to prednisone and the correct handling of injuries.

Resumo: Introdução: a hanseníase é uma doença infecciosa crônica causada pelo Mycobacterium leprae, que acomete principalmente pele e nervos periféricos. As reações hansênicas são eventos agudos que estão associados ao aumento da morbimortalidade da doença. Objetivo: apresentar o caso de um paciente com fenômeno de Lúcio, por meio do qual se chegou ao diagnóstico de hanseníase, e ressaltar a importância de se ter em mente esta doença, rara em nosso meio, para seu correto diagnóstico. Discussão: o fenômeno de Lúcio é um tipo de reação hansênica mediada por imunocomplexos. Caracteriza-se clinicamente por máculas ou placas eritêmato-violáceas de início súbito que evoluem para úlceras necróticas e cicatrizam, deixando cicatrizes estreladas atróficas. Sem tratamento pode ser fatal, devido a superinfecção e sepse; a terapia está baseada no tratamento específico da infecção, associado à prednisona e no manejo correto da ferida.

Salmonella-induced immune response reduces recurrence and tumor dissemination in preclinical melanoma model.

Localized melanoma is easy to remove by surgery, resulting in a high five-year relative survival rate. However, when disseminated the disease management is challenging. The use of immunotherapies, such as anti-checkpoint monoclonal antibodies, has improved treatment options but still only a small percentage of patients responds to these expensive treatments. In this work, we apply a bacteria-based immunotherapy using LVR01, an attenuated Salmonella enterica serovar Typhimurium, as neoadjuvant therapy one week before surgery in a preclinical disseminated murine melanoma model. LVR01 administration resulted in tumor growth retardation prior to tumor resection, due to a rapid upregulation of inflammatory genes in the tumor microenvironment. As a consequence, cell infiltration increased, particularly neutrophils, macrophages and NK cells, being the latter involved in Salmonella anti-tumor activity. Besides, tumor-draining lymph node infiltration is characterized by reinvigorated CD4+ and CD8+ lymphocytes. Induced immune response could account for the prevention or delay of tumor recurrence and appearance of metastasis, resulting in a prolonged overall survival after surgery. Furthermore, upon rechallenge mice show partial protection, suggesting the existence of specific memory against melanoma. We propose that neoadjuvant LVR01 treatment could represent an interesting inexpensive alternative that may ease tumor resection, while preventing tumor recurrence in patients with melanoma.

Preclinical Evaluation of LVR01 Attenuated Salmonella as Neoadjuvant Intralesional Therapy in Combination with Chemotherapy for Melanoma Treatment.

Treatment of malignant melanoma has improved in the last few years owing to early detection and new therapeutic options. Still, management of advanced disease remains a challenge because it requires systemic treatment. In such cases, dacarbazine-based chemotherapy has been widely used, despite low efficacy. Neoadjuvant therapies emerge as alternative options that could help chemotherapy to achieve increased benefit. In this work, we evaluate LVR01, an attenuated Salmonella enterica serovar typhimurium, as neoadjuvant intralesional therapy in combination with dacarbazine in a preclinical melanoma model. B16F1 melanoma‒bearing mice received intraperitoneal administration of dacarbazine for 3 consecutive days. LVR01 treatment, consisting of one single intratumoral injection, was applied 1 day before chemotherapy began. This therapeutic approach retarded tumor growth and prolonged overall survival, revealing a strong synergistic antitumor effect. Dacarbazine induced a drastic reduction of secondary lymphoid organ cellularity, which was partially restored by Salmonella, particularly potentiating activated cytotoxic cell compartments. Systemic immune reactivation could be a consequence of the intense inflammatory tumor microenvironment induced by LVR01. We propose that the use of LVR01 as neoadjuvant intralesional therapy could be considered as an interesting strategy with close clinical application to boost chemotherapy effect in patients with melanoma.

Creation of a pioneering interdisciplinary genital dermatology unit for Hispanic men: First 269 patients.

The role of circumcision in partially protecting against sexually transmitted infections (STIs) and other dermatoses has been documented. Neonatal circumcision is not routinely practiced in South America. Although it is logical to assume that male genital dermatoses are more prevalent in Hispanic men, they are underrepresented in the existing literature. Objective: To describe the epidemiological characteristics from our male genital dermatology unit in Montevideo (Uruguay), the diagnoses, and correlate them with circumcision status and comorbidities. Methods: A retrospective observational cohort study was conducted. A dermatologist and urologist evaluated all patients using standard questionnaires. In 3 years and 8 months, 269 patients were seen. Median age was 41, prevalence of neonatal circumcision was 0.7%, HIV was 4.2%, STIs were 24.9%, non-STIs were 63.9%, and both (STI + non-STI) were 11.2%. Most frequent entities: eczema/balanoposthitis (27.1%), condyloma (24.9%), and lichen sclerosus (15.6%). Data correlating circumcision and other diagnoses did not reach statistical significance. HIV was positively associated with other STIs (p < 0.05), and an association with balanoposthitis was seen; however, it did not reach statistical significance (p < 0.1). Main limitation was small sample size. This is the first study of its kind based on Hispanic patients. Collaboration between specialties proved to be fundamental. Further studies are needed in this demographic to find an association between circumcision, comorbidities, and genital dermatoses.

Platelet-rich plasma for male genital lichen sclerosus resistant to conventional therapy: First prospective study.

Ultrapotent topical corticosteroids and circumcision are usually effective for male genital lichen sclerosus (MGLSc); however, refractory cases are often referred to our Male Genital Dermatology Unit. Treatment with autologous platelet-rich plasma (TPRP) has recently been advocated as a safe and effective treatment option, but there have been no prospective studies in men to date. The objective of this study is to assess the safety and efficacy of TPRP for MGLSc resistant to conventional therapy. A prospective, open-label, single-arm, therapeutic study was carried out in this study. Inclusion criteria: resistant to conventional therapy for at least 6 months. Procedure: infiltration of 0.1 mL/cm2 PRP every 8 weeks. Monthly data recording: visual appearance with photographs and external scoring by an expert using Investigator's Global Assessment Scale (IGA scale 0-5), symptoms (scale 0-5), quality of life (QoL; Dermatology Life Quality Index [DLQI]), and complications. No. of patients included was n = 5. No. of patients excluded during treatment was n = 1. Mean initial IGA: 3.6. Mean initial DLQI: 6. TPRP n = 34 (range: 2-9; average: 6.8 per patient). Mean IGA at 18 months: 3.25. Mean DLQI at 18 months: 1.25. All patients reported being completely asymptomatic at 10 months. No. of patients with complications is n = 1 (balanitis). TPRP seems to be safe and effective, regarding symptom control and improvement in QoL; however, visual changes were minimal.

TLR7 agonist in combination with Salmonella as an effective antimelanoma immunotherapy.

AIM: We evaluated a novel approach combining the use of attenuated Salmonella immunotherapy with a Toll-like receptor agonist, imiquimod, in B16F1 melanoma-bearing mice. MATERIALS & METHODS: B16F1 melanoma-bearing mice were daily treated with topical imiquimod in combination with one intratumoral injection of attenuated Salmonella enterica serovar Typhimurium LVR01. RESULTS: The combined therapy resulted in retarded tumor growth and prolonged survival. Combination treatment led to an enhancement in the expression of pro-inflammatory cytokines and chemokines in the tumor microenvironment, with a Th1-skewed profile, resulting in a broad antitumor response. The induced immunity was effective in controlling the occurrence of metastasis. CONCLUSION: Salmonella LVR01 immunotherapy in combination with imiquimod is a novel approach that could be considered as an effective antimelanoma therapy.

The Clinician Faced With Anticochlear Antibodies: What to Do With Them?

BACKGROUND: Autoimmune inner ear disease as a cause of sensorineural hearing loss is a poorly understood entity. Thus, the role of anticochlear antibodies (ACLAs) in clinical management is still not well established. OBJECTIVE: The aims of this study were to describe the use of ACLAs in our clinical setting and to understand the clinicians' therapeutic approach in these cases. We also analyzed the usefulness of these autoantibodies in clinical practice. METHODS: A retrospective study with nonprobabilistic convenience sampling of patients who were tested for ACLAs in the period from January 1, 2013, to December 31, 2015, was performed. The study was carried out in 2 stages: (1) medical records of all patients who were investigated for ACLAs were reviewed. The following variables were analyzed: age, sex, reason for requesting ACLAs, concomitant autoimmune disease, audiogram, immunosuppressive treatment, duration of treatment, and clinical response; (2) patients who received immunosuppressive therapy were contacted by telephone. A visual analog scale (VAS) (0-10) was applied to evaluate the therapeutic response. RESULTS: Thirty-nine patients who were investigated for ACLAs were identified. The mean age was 41 (SD, 16) years; there were 33 female patients. Of the 34 patients with ACLA-positive antibodies, 16 patients received immunosuppressive agents, of for management of their sensorineural hearing loss, corticosteroids was the most commonly used treatment. No clinical improvement was reported by patients after immunosuppressive treatment in this subgroup. CONCLUSIONS: The role of ACLAs in the diagnosis and management of sensorineural hearing loss remains unclear. In this small study at a single institution, ACLA testing may not have improved the outcome of sensorineural hearing loss.

Community-associated methicillin-resistant Staphylococcus aureus in children treated in Uruguay.

INTRODUCTION: Staphylococcus aureus produces a variety of diseases among children, ranging from skin and soft tissue infections to invasive life-threatening diseases. Since 1990, an increasing number of diseases produced by community-associated methicillin-resistant S. aureus (CA-MRSA) isolates have been reported. The aim of this study was to describe the importance and the microbiological characteristics of S. aureus isolates recovered from children treated at the Hospital Pediátrico del Centro Hospitalario "Pereira Rossell" (HP-CHPR); focusing on invasive diseases caused by CA-MRSA isolates, as well as some clinical aspects of the diseases they have produced. METHODOLOGY: One hundred and twenty-five S. aureus isolates recovered from the HP-CHPR between 2003 and 2006 from children with invasive (n=89) and superficial diseases (n=36) were included. Genotypic and phenotypic characteristics of S. aureus isolates and relevant clinical aspects of each child were studied. RESULTS: CA-MRSA isolates accounted for 73% of all S. aureus recovered from invasive (mainly bone and joint) infections, pneumonia and bacteraemia. The most common CA-MRSA strain recovered from invasive (n=65) and superficial (n=36) diseases had the following features: pulsotype A (type USA1100), SCCmec cassette type IV, Panton-Valentine Leukocidin genes positive, susceptibility to trimethoprim-sulfamethoxazole without the inducible macrolide-lincosamide-streptogramin B (iMLSB) resistance phenotype. No association between genotypic characteristics of invasive CA-MRSA isolates and clinical outcomes was found. CONCLUSIONS: CA-MRSA isolates produced a wide spectrum of invasive diseases in a public paediatric hospital between 2003 and 2006. Microbiologic characterization suggests the spread of an adapted CA-MRSA clone lacking erm genes.

Reacciones adversas cutáneas a medicamentos: Vigilancia durante un año en un Hospital Universitario. Uruguay 2008-2009 / Adverse cutaneous reactions to Drugs among hospitalized patients: A one year surveillance

Background: Adverse cutaneous reactions to Drugs (CDRs) are of particular interest among all adverse Drug reactions (ADR) due to their frequency, potential severity and because of the importance of an early diagnosis. Antimicrobial agents, anticonvulsants and non-steroidal anti-inflammatory Drugs are the Drugs associated to the highest risk of CDRs. Aim: To assess CDRs in hospitalized patients and identify the Drugs involved. Material and Methods: All patients hospitalized in the Hospital de Clínicas in Montevideo, Uruguay, with suspected CDRs, detected during one year, were included in this prospective study. The imputability was established using the Karch and Lasagna algorithm modified by Naranjo. We analyzed age, gender, Drugs involved, causal disease, severity, latency and evolution. Results: Seventeen patients, aged 17 to 85 years (15 females) with CDRs were identifed. Twelve had morbilliform exanthemas, four had reactions with eosinophilia and systemic symptoms and one had a Stevens Johnson syndrome. The Drugs involved were antimicrobials in nine cases, hypouricemic agents in four cases, anticonvulsants in three cases and aspartic insulin in one. Twelve patients had a life threatening reaction and one required admission to the intensive care unit. No deaths occurred. Conclusions: CDRs were more common in women and most of them were caused by antimicrobial agents.

[Adverse cutaneous reactions to drugs among hospitalized patients: a one year surveillance]. / Reacciones adversas cutáneas a medicamentos: Vigilancia durante un año en un Hospital Universitario. Uruguay 2008-2009.

BACKGROUND: Adverse cutaneous reactions to Drugs (CDRs) are of particular interest among all adverse Drug reactions (ADR) due to their frequency, potential severity and because of the importance of an early diagnosis. Antimicrobial agents, anticonvulsants and non-steroidal anti-inflammatory Drugs are the Drugs associated to the highest risk of CDRs. AIM: To assess CDRs in hospitalized patients and identify the Drugs involved. MATERIAL AND METHODS: All patients hospitalized in the Hospital de Clínicas in Montevideo, Uruguay, with suspected CDRs, detected during one year, were included in this prospective study. The imputability was established using the Karch and Lasagna algorithm modified by Naranjo. We analyzed age, gender, Drugs involved, causal disease, severity, latency and evolution. RESULTS: Seventeen patients, aged 17 to 85 years (15 females) with CDRs were identifed. Twelve had morbilliform exanthemas, four had reactions with eosinophilia and systemic symptoms and one had a Stevens Johnson syndrome. The Drugs involved were antimicrobials in nine cases, hypouricemic agents in four cases, anticonvulsants in three cases and aspartic insulin in one. Twelve patients had a life threatening reaction and one required admission to the intensive care unit. No deaths occurred. CONCLUSIONS: CDRs were more common in women and most of them were caused by antimicrobial agents.

Characteristics of Community-Associated Methicillin-Resistant Staphylococcus aureus (CA-MRSA) Strains Isolated from Skin and Soft-Tissue Infections in Uruguay.

We analyzed 90 nonduplicates community-associated methicillin-resistant S. aureus (CA-MRSA) strains isolated from skin and soft-tissue infections. All strains were mecA positive. Twenty-four of the 90 strains showed inducible macrolide-lincosamide-streptogramin B resistance. All strains produced alpha-toxin; 96% and 100% of them displayed positive results for lukS-F and cna genes, respectively. Eigthy-five strains expressed capsular polysaccharide serotype 8. Six different pulsotypes were discriminated by pulsed-field gel electrophoresis (PFGE) and three predominant groups of CA-MRSA strains (1, 2, and 4) were identified, in agreement with phenotypic and genotypic characteristics. Strains of group 1 (pulsotype A, CP8+, and Panton-Valentine leukocidin (PVL)+) were the most frequently recovered and exhibited a PFGE band pattern identical to other CA-MRSA strains previously isolated in Uruguay and Brazil. Three years after the first local CA-MRSA report, these strains are still producing skin and soft-tissue infections demonstrating the stability over time of this community-associated emerging pathogen.

Surveillance of antibiotic resistance evolution and detection of class 1 and 2 integrons in human isolates of multi-resistant Salmonella Typhimurium obtained in Uruguay between 1976 and 2000.

OBJECTIVES: To study the evolution of antibiotic resistance in isolates of Salmonella enterica subspecies enterica serovar Typhimurium (Salmonella Typhimurium) obtained in Uruguay between the years 1976 and 2000, and to determine the incidence of class 1 and 2 integrons in the multi-resistant isolates. METHODS: We studied 258 strains of Salmonella Typhimurium from various sources, isolated between 1976 and 2000. We determined the evolution of antibiotic resistance and the distribution of class 1 and 2 integrons in all isolates by means of disk diffusion assays and PCR. RESULTS: During the period 1989-2000 resistance to streptomycin was 56.8%, tetracycline 13.6%, sulfonamides 11.2%, and ampicillin 7.2%. Resistance to gentamicin, kanamycin, chloramphenicol, and nalidixic acid were lower than 5%; no resistance was detected to fluoroquinolones, oxyiminocephalosporins, and amikacin. These results show a dramatic decrease with respect to values found in the period 1976-1988. In this period, resistance to streptomycin was 63.2%, tetracycline 36.8%, sulfonamides 32.3%, and ampicillin 27.8%. Throughout the two periods, 29 multi-resistant Salmonella Typhimurium strains were isolated harboring some class of integron: 15 strains had only intI2, 11 strains presented both intI1 and intI2, and three isolates only intI1. CONCLUSIONS: Our results show a marked decrease in resistance throughout these years, along with a correlation between resistance to different antibiotics and the presence of integrons.