Atypical Cutaneous Leishmaniasis Variant.

Leishmaniasis is a complex group of parasitic infectious diseases caused by intracellular protozoa of the genus Leishmania. It is a zoonosis mainly transmitted by the bite of infected female Phlebotomus or Lutzomyia sandflies. Clinical manifestations of leishmaniasis are diverse and can range from asymptomatic presentations to disseminated systemic disease. Cutaneous leishmaniasis is endemic in more than 80 countries in the world, having a predominance in tropical and subtropical regions. Although the majority of cases follow a classic development, an increasing number of new and rare variants of cutaneous leishmaniasis have been reported. These variants should be suspected as a cause of diverse clinical presentations, especially in endemic regions and travelers, being a diagnostic challenge for physicians. We present a case of atypical cutaneous leishmaniasis found as a single verrucous plaque of eight months of evolution in the left posterior thigh of a 35-year-old man, who presented mild pruritus. The patient reported shrimp farming as his main occupational activity and was living in a rural region surrounded by forest on the Pacific coast of Ecuador. On dermatological examination, a single 4 x 5 cm verrucous plaque with irregular borders and a scaly erythematous violaceous aspect was found. Histopathological analysis revealed the presence of lymphohistiocytic inflammatory infiltrate with plasmocytes and granulomatous inflammation. On the Giemsa stain, intracellular amastigotes (Leishman-Donovan bodies) were observed. The treatment consisted of intramuscular meglumine antimoniate, presenting significant improvement on follow-up.

Factors associated with active tuberculosis in Colombian patients with systemic lupus erythematosus: a case-control study.

OBJECTIVE: To identify factors associated with active tuberculosis (TB) in patients with systemic lupus erythematosus (SLE). METHODS: We performed a retrospective case-control study in two tertiary care teaching hospitals in Medellín, Colombia. From January 2007 to December 2017, a total of 268 patients with SLE were included. SLE patients with TB (cases) were matched 1:3 with SLE patients without TB (controls) by disease duration and the date of the hospitalization in which the diagnosis of TB was made (index date of cases) to the nearest available rheumatology hospitalization in the matched controls (± 2 years). Conditional univariable and multivariable logistic regression analyses were performed. RESULTS: Sixty-seven cases and 201 controls were assessed. Only pulmonary TB occurred in 46.3%, only extrapulmonary TB in 16.4% and disseminated TB in 37.3% of cases. Multivariable logistic regression analysis showed that lymphopenia (OR, 2.91; 95% CI 1.41-6.03; P = 0.004), 12-month cumulative glucocorticoid dose ≥ 1830 mg (OR, 2.74; 95% CI 1.26-5.98; P = 0.011), and having been treated with ≥ 2 immunosuppressants during the last 12 months (OR, 2.81; 95% CI 1.16-6.82; P = 0.022) were associated with TB after adjusting for age, sex, ethnicity, disease duration, disease activity, and comorbidity index. A trend towards an association of kidney transplantation with TB was also found (OR, 3.77; 95% CI 0.99-14.30; P = 0.051). CONCLUSION: Among SLE patients, cumulative glucocorticoid dose, lymphopenia, and the use of ≥ 2 immunosuppressants during the last 12 months were associated with active TB infection. Key Points • Among SLE patients, a cumulative dose of glucocorticoids equivalent to 5 mg/day of prednisone during the last 12 months is independently associated with the development of TB. • The use of two or more immunosuppressants during the last 12 months is also a risk factor for TB infection development is SLE patients. • Lymphopenia is predominant in SLE patients with TB, being especially profound in those with disseminated TB. • Renal transplant recipients with SLE also have an elevated risk of TB.

Acute myopericarditis as primary manifestation of urogenital reactive arthritis by Staphylococcus haemolyticus metilcilino resistant / Miopericarditis aguda como manifestación primaria de artritis reactiva urogenital por Staphylococcus haemolyticus resistente a meticilina

Reactive arthritis describes the relationship between the host and the environment. This leads to urogenital or gastrointestinal infections. It clinically presents with inflammatory lumbosacral pain, asymmetric oligoarthritis and enthesitis of the Achilles tendon and plantar fascia. Among the extra-articular manifestations are acute anterior uveitis, skin lesions, genital lesions, and oral ulcers, with the rarest being cardiovascular. A case is presented of a patient with a urogenital infection and cardiovascular manifestations, interpreted and managed as acute coronary syndrome. After further studies an acute myopericarditis was considered as a primary manifestation of reactive arthritis.

La artritis reactiva describe la interrelación entre el hospedero y el medio ambiente. Aparece después de infecciones urogenitales o digestivas. Clínicamente presenta dolor lumbosacro inflamatorio, oligoartritis asimétrica y entesitis del tendón de Aquiles y la fascia plantar. Entre las manifestaciones extraarticulares, se encuentran la uveítis anterior aguda, lesiones en piel, lesiones genitales y úlceras orales. Las más infrecuentes son las cardiovasculares. Describimos el caso de un paciente con infección urogenital y manifestaciones cardiovasculares interpretadas y manejadas como síndrome coronario agudo, pero que a la luz de estudios posteriores se consideró finalmente una miopericarditis aguda como manifestación primaria de una artritis reactiva.

Safety, pharmacokinetics and antiviral effect of BILB 1941, a novel hepatitis C virus RNA polymerase inhibitor, after 5 days oral treatment.

BACKGROUND: BILB 1941 is a potent and specific nonnucleoside inhibitor of the hepatitis C virus (HCV) RNA polymerase in vitro. METHODS: In a double-blind sequential group comparison, 96 male HCV genotype 1 patients with minimal to mild liver fibrosis (Ishak or Metavir score 0-2) were randomized (8 to active treatment and 2 to placebo per dose group) and treated with 10-450 mg BILB 1941 every 8 h over 5 days. Viral load (VL) was measured using Roche Cobas TaqMan assays. RESULTS: VL decreased by > or =1 log10 IU/ml in 2/8, 2/8, 1/8, 2/7, 0/8, 2/8 and 4/5 patients on 60, 80, 100, 150, 200, 300 and 450 mg, respectively. No response was seen with placebo. HCV subtype 1b showed better response than 1a, the effect of other covariables including prior interferon treatment was not significant. NS5B population sequencing and phenotyping identified baseline samples with reduced BILB 1941 susceptibility, but did not detect an on-treatment emergence of resistant mutants. Plasma drug levels were linear until 300 mg. No serious adverse events (AEs) were reported. AEs were mainly gastrointestinal-related (most frequent diarrhoea) and frequency increased with dose. On 450 mg, all five active-treated patients discontinued (four for gastrointestinal intolerance and one for increased aspartate aminotransferase and alanine aminotransferase levels) and the trial was discontinued. CONCLUSIONS: BILB 1941 monotherapy demonstrated antiviral activity against HCV genotype 1, but gastrointestinal intolerance precluded testing of higher doses.

[Adefovir dipivoxil compassionate use program in Spain: efficacy and resistance analysis]. / Programa de uso compasivo con adefovir dipivoxil en España: valoración de su eficacia y estudio de las resistencias.

BACKGROUND AND OBJECTIVE: The extended treatment with lamivudine in patients with chronic hepatitis B is associated with the emergence of resistances. Patients with resistance to lamivudine show a loss of biochemical and virological responses and a higher progression of their liver disease. Adefovir dipivoxil, an analogue of the nucleotides, is effective for the treatment of patients with resistance to lamivudine. The aim of this study was to evaluate the efficacy, safety and resistance of adefovir dipivoxil in patients with chronic hepatitis B refractory to treatment with lamivudine. PATIENTS AND METHOD: One hundred and twenty hepatits B virus patients refractory to lamivudine were treated with adefovir dipivoxil. Seventy-four patients were followed up during two years. In all cases, the hepatitis B virus-DNA was determined by polymerase chain reaction, and in those cases without response to treatment, the presence of resistances to adefovir and lavimudine were studied. RESULTS: At the second year of treatment, we observed a biological response of 54.1%, a biochemical response of 62.2%, while an elimination of hepatitis B e antigen was seen in 21% cases. 20% patients developed resistance to adefovir dipivoxil, and the most frequent detected mutations were: A181V, A181T and N236T. Drug safety was excellent; in fact, only one adverse effect related to the drug was detected. CONCLUSIONS: Treatment with adefovir dipivoxil for 2 years in mono-therapy in patient who are previously non-responders to lavimudine is associated with a high biochemical and virologycal response with an excellent safety. At the second year of treatment, the adefovir dipivoxil resistance rate is 20%.

Peginterferon-alfa2a plus ribavirin for 48 versus 72 weeks in patients with detectable hepatitis C virus RNA at week 4 of treatment.

BACKGROUND & AIMS: Patients with chronic hepatitis C who do not respond rapidly to therapy have a low chance of developing a sustained virologic response (SVR) when treated for 48 weeks. This study investigated whether treatment for 72 weeks increases the rate of SVR in patients with detectable hepatitis C virus (HCV)-RNA levels at week 4 of treatment. METHODS: A total of 510 treatment-naive patients were treated with peginterferon-alfa2a (180 microg/wk) plus ribavirin (800 mg/day). Patients with detectable HCV-RNA levels at week 4 (n = 326) were randomized to complete 48 (group A, n = 165) or 72 weeks (group B, n = 161) of treatment. Patients with undetectable HCV-RNA levels at week 4 (n = 184) were allocated into group C (n = 148) or group D (n = 36), according to HCV genotype and baseline viremia, and treated for 24 or 48 weeks, respectively. All patients were followed-up for 24 weeks after the end of treatment. RESULTS: The end-of-treatment response rate (61%) was similar in groups A and B, but the SVR rate was higher in group B (45% vs 32% in A; P = .01). In genotype 1-infected patients randomized to group A (n = 149) or B (n = 142), SVR rates were 28% and 44%, respectively (P = .003). The incidence of adverse events was similar in all groups. Treatment discontinuation was more frequent in group B (36%) than in group A (18%) (P = .0004). SVR rates in groups C and D were 79% and 64%, respectively. CONCLUSIONS: Extension of treatment with peginterferon-alfa2a plus ribavirin from 48 to 72 weeks significantly increases the rate of SVR in patients with detectable viremia at week 4 of treatment.

Survival on chronic dialysis: 10 years' experience of a single Colombian center.

Using a retrospective cohort study, we evaluated survival and mortality risk factors in our dialysis population at the Renal Unit, RTS Cauca--Nephrologic San Jose, Popaydn, Cauca, Colombia. In the study, we included patients with chronic renal failure who started dialysis therapy during the period 1994-1999, and who remained on dialysis for a minimum of 5 years. Endpoints (living, died, lost to follow-up) were evaluated at the end of the study (July 2004), and a Kaplan-Meier survival analysis was performed. Mortality risk was analyzed using the multivariate Cox proportional hazard model. The study included 236 patients (129 on peritoneal dialysis and 107 on hemodialysis), whose mean age (+/- standard deviation) was 54.5 +/- 15.6 years. Of the group, 51% were women, 68.7% were urban dwellers, and 31.3% were rural dwellers. Major causes of end-stage renal disease included chronic glomerulonephritis (43.2%), diabetic nephropathy (35.7%), and hypertensive nephropathy (6.0%). The racial origins of the study population were half-caste (80.7%), Afro-Colombian (8.8%), indigenous (7.6%), and white (2.6%). Median (+ standard error) survival on hemodialysis was 66 +/- 10 months. Median survival on peritoneal dialysis was 57 +/- 7 months. Among patients with diabetes, median survival on hemodialysis was 40 +/- 13 months, and on peritoneal dialysis, it was 38 +/- 4 months. Major causes of mortality included sudden death (40%), infection (25%), and cardiovascular causes (22.5%). Significant mortality risk factors for hemodialysis patients were congestive heart failure (p = 0.01) and albumin <3 g/dL (p = 0.01). For peritoneal dialysis patients, the significant risk factors were diabetes mellitus (p = 0.01) and albumin < 2.5 g/dL (p = 0.02). Patient survival in our setting is similar to that reported in other series. The strongest predictive factors for mortality were diabetes mellitus, congestive heart failure, anemia, and hypoalbuminemia.

Comparison of immunophenotypes in the blood of patients on continuous ambulatory peritoneal dialysis, asymptomatic and with peritonitis.

Peritonitis is a complication of continuous ambulatory peritoneal dialysis (CAPD) that often causes fibrosis. Understanding the role played by the immune system is required if we are to understand the mechanisms of defense and tissue lesion triggered by germs. We compared the characteristics of the blood immunophenotypes of patients on CAPD, with and without peritonitis. This descriptive, prospective study was carried out in the dialysis unit of San José University Hospital, a tertiary care institution in Popayán, Colombia. In blood samples from 46 patients on CAPD (26 with peritonitis and 20 without peritonitis), we used flow cytometry to measure cytokine production at the single-cell level. The diagnosis of peritonitis was made by standard clinical and laboratory criteria. We noted general clinical characteristics of the patients; percentages of lymphocytes, monocytes, neutrophils, and eosinophils; and cell counts of lymphocytes (CD4 cells, CD8 cells) and their subsets [B1, B2, and natural killer (NK) cells]. We also determined the CD4:CD8 ratio. We found significant differences in the levels of serum albumin (p < 0.001), the percentages of lymphocytes (p < 0.04) and neutrophils (p < 0.04), and the counts of B1 and B2 cells, especially in patients whose CD4:CD8 ratio was below 1.2. Those patients also had more intense CD4 lymphopenia, more CD8 cells (principally T-suppressor cells), and more expansion of NK cells. In patients on CAPD, an important immune activation and rise in the percentage of B1 cells occurs that increases with peritonitis. Among the general clinical characteristics, albumin was the only one to show a statistically significant difference between patients with and without peritonitis. An important CD4 lymphopenia occurred in patients with a CD4:CD8 ratio below 1.2.

Cytokines and peritonitis in continuous ambulatory peritoneal dialysis: immunodeviation and immunodeficiency.

Cytokines are soluble mediators of the immune system, which regulate the immune response to antigenic stimuli. In continuous ambulatory peritoneal dialysis (CAPD) patients with peritonitis, an inflammatory process occurs, but the patterns of cytokine secretion have not yet been clarified. We compared the characteristics of the intracellular production of cytokines and looked for the immunophenotypes T helper 1 (TH1), T helper 2 (TH2), and T helper 0 (TH0) in CAPD patients with and without peritonitis. Our descriptive, prospective study was carried out in the dialysis unit of the San José University Hospital, a tertiary health care center in Popayán, southwest Colombia. We obtained 28 peripheral blood samples from CAPD patients (8 with peritonitis and 20 without peritonitis) and processed them by flow cytometry for intracellular detection of cytokines. The peritonitis diagnosis was made based using established clinical and laboratory criteria. We measured the general clinical characteristics and percentage of intracellular production of interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-12 (IL-12), tumor necrosis factor alpha (TNF alpha), interleukin-4 (IL-4), and interferon-gamma (INF-gamma) in T lymphocytes. Diabetic nephropathy and chronic glomerulonephritis were the most frequent primary pathologies in both groups of patients. The patients on CAPD without peritonitis expressed high levels of CD69 and the pro-inflammatory cytokines IL-1, IL-6, IL-12, TNF alpha, and IL-4, indicating in vivo immune activation similar to the group with peritonitis. In the group without peritonitis, 95% of samples displayed immunodeviation TH2. Just 5% of samples approached TH0, producing IFN-gamma. After mitogen activation, 45% of the samples stayed in TH2; 55% approached TH0. Patients with peritonitis produced high levels of IL-4 and little IFN-gamma, which indicates immunodeviation TH2 in 75% of samples; 25% approached TH0. When cells were stimulated by ionomicin and phorbol 12-myristate 13-acetate (PMA), more IFN-gamma appeared and high levels of IL-4 persisted in 75% of the samples, which looked like intent to correct the TH2 immunodeviation toward TH0. Patients on CAPD with and without peritonitis showed immune activation per se and high production of pro-inflammatory cytokines accompanied by a strong pattern of cytokine TH2 and a deficiency of IFN-gamma production, suggesting heavy immunodeviation TH2 and immunodeficiency TH1 (owing to the deficit of IFN-gamma). Finally, with in vitro immune stimulation, the TH2 pattern tried to approach TH0.

Peritonitis in continuous ambulatory peritoneal dialysis: cytokines in peritoneal fluid and blood.

Cytokines are soluble mediators of the immune system that regulate the response to antigens and microorganisms. In patients on continuous ambulatory peritoneal dialysis (CAPD) who have peritonitis, an inflammatory process exists that must be understood if susceptibility to, and the mechanisms of, complications such as fibrosis and others are to be understood. To that end, we studied 9 CAPD patients with peritonitis. The case series was conducted in Popayán, Colombia, at the RTS Cauca dialysis unit and the University of Cauca hospital, a tertiary health care facility. Peritonitis was diagnosed by standard clinical and laboratory criteria. Using flow cytometry, we measured the percentage production of intracellular cytokines [interleukin-1 alpha (IL-1 alpha), IL-6, IL-12, tumor necrosis factor alpha (TNF alpha), IL-4, and interferon-gamma (IFN-gamma) in T lymphocytes from blood and peritoneal fluid. Among the studied patients, all (100%) produced high levels of IL-1, IL-6, TNF alpha, IL-12, and IL-4 in both fluids (blood: 89% +/- 63% of cells; peritoneal fluid: 81.6% +/- 10.1% of cells). In blood, 25% of patients produced IFN-gamma (mean: 15.7% of cells), showing that 75% of patients had the TH2 pattern, and 25% were close to TH0. In peritoneal fluid, 34% of patients produced IFN-gamma spontaneously (mean: 24.5% of cells), indicating that 66% of patients were TH2, and 34% were close to TH0. After stimulation, expression of cytokines, including IFN-gamma (39% of T cells), was increased, and high production of IL-4 indicated that 25% of patients were TH2, and 75% were TH0. In peritoneal fluid, production of cytokines, including IFN-gamma, was increased, with high production of IL-4, indicating switching from TH2 (34% of patients) to TH0 (66% of patients). Of the studied patients, 35% had a CD4:CD8 ratio < 1.1 in blood, and also produced IL-12 (94.5% of cells) and IFN-gamma (30% of cells), as compared with patients in whom the CD4:CD8 ratio was > 1.2. Patients on CAPD who have peritonitis produce large amounts of pro-inflammatory and TH2 cytokines. More IFN-gamma is produced in peritoneal fluid than in blood, which suggests more inflammation. Immunodeviation TH2 is seen in blood and peritoneal fluid of CAPD patients with peritonitis. Patients with a CD4:CD8 ratio < 1.1 produce more IFN-gamma and IL-12, and are more able to switch from TH2 to TH0.

Immunophenotyping by flow cytometry of peritoneal fluid of patients with peritonitis on continuous ambulatory peritoneal dialysis.

Our project identified, by flow cytometry, the immunophenotypes and activation state of the immune cells in the peritoneal dialysis fluid from patients with peritonitis on continuous ambulatory peritoneal dialysis. The results showed that all kinds of cells of the immune system were present in the peritoneal fluid in percentages and activation states similar to those seen in blood. Also, two subgroups of patients were noted, according to CD4:CD8 ratio. Patients whose ratio was < 1.1 had more expansion of CD8 and NK cells, and a higher percentage of B1 cells in both fluids than were seen in healthy people.

[Induction therapy with interferon alfa-2a in compensated hepatitis C virus-related cirrhosis. Randomized, multicenter study]. / Terapia de inducción con interferón alfa-2a en la cirrosis por el virus de la hepatitis C compensada. Estudio multicéntrico aleatorizado.

BACKGROUND: Although standard dose interferon (IFN) is successful in only 5% of patients with compensated hepatitis C virus (HCV)-related cirrhosis, it has been suggested that this therapy might decrease the risk of complications or the incidence of hepatocellular carcinoma. Based on HCV kinetics, daily IFN may improve response rates. PATIENTS AND METHOD: Forty cirrhotic patients were randomised to receive (Group I: 19) or not (Group II: 21) treatment with IFN (4.5 MU/daily for 24 weeks, followed by 4.5 MU/48 hours for a further 24 weeks period, only if ALT was within normal values). RESULTS: Dose reduction and discontinuation for adverse events was required in 11 (58%) and 6 (31.5%) cases, respectively. End-of-treatment response was not observed in any of the 21 controls but in 4 of the 19 (21%) treated patients (p = 0.04); a sustained response was achieved in only 2 treated patients (10.5%). The 3-year probability of developing any of the following: ascites, hepatocellular carcinoma, transplantation or death was lower in Group I than in Group II (6% vs 27%; p = 0.05). CONCLUSION: Although induction IFN therapy is associated with common side effects and poor sustained response in compensated HCV-related cirrhosis, it might improve the outcome of patients at the medium-term.