Marina Khoury

Neutropenia and the development of the systemic inflammatory response syndrome

Abstract Objective. To determine outcome and natural course of systemic inflammatory response syndrome (SIRS) stages in adult febrile neutropenic patients. Design and setting. Retrospective cohort study in the medicine department and intensive care unit of a university hospital. Patients. Adults with cancer-related neutropenia and community-acquired fever. Measurements and results. Patients were classified on admission according to SIRS parameters, tumor type, and degree of neutropenia. Records of clinical and laboratory data during hospitalization were reviewed. Univariate and logistic regression analyses were performed. Seventy-nine events in 62 patients were analyzed. Overall mortality rate was 20.2% (16/79). Mortality increased as SIRS stage worsened on admission. No patients with stage 2 SIRS died (neutropenia and fever alone) but 11.1% of patients with SIRS 3, 43.4% with SIRS 4, 66.6% with sepsis induced hypotension, and 90% with septic shock. SIRS stage on admission was an independent predictor of death and was related directly to rate of progression to shock, i.e., none of the patients with SIRS 2, 2.7%(1/36) of those with SIRS 3, and 30.4% (7/23) of those admitted with SIRS 4. Conclusions. Mortality and progression to septic shock increased as more SIRS criteria were met on admission. SIRS stages could serve as a risk-assessing model in febrile neutropenic patients.

Reactivation of Ocular Toxoplasmosis in Non-Hispanic Persons, Misiones Province, Argentina.

To the Editor: Ocular toxoplasmosis (OT), caused by the parasite Toxoplasma gondii, is known to be a major health problem in South America, especially in Colombia and Brazil (1–3). The highest prevalence of OT has been reported in Erechim, Rio Grande do Sul, Brazil, a state that borders Uruguay and Argentina, where a representative population-based household survey showed that 17.7% of 1,042 adults examined had OT (1). For comparison, it is estimated that ≈2% of T. gondii–infected persons in the United States manifest OT (4). It is still unclear whether the high rate of OT in South America is attributable to host or parasite genetic factors or differences in exposure rate (5,6). In the province of Misiones in Argentina, the prevalence of OT in patients seeking care in an ophthalmic office is also high and has been documented as high as 20% (7). The area was mostly settled in the early 20th century by non-Hispanic European immigrants from Germany and Slavic countries who arrived through Southern Brazil. We explored the relationship between ethnic origin and frequency of reactivation toxoplasmic retinochoroiditis (RTR) in patients who sought care in a private secondary care eye clinic in Obera, Misiones, Argentina, during February 2004–May 2014. All patients with uveitis were examined by a single uveitis specialist (M.R.), who performed complete ophthalmological examinations, including visual acuity, anterior biomicroscopy, tonometry, and indirect ophthalmoscopy. Study inclusion criteria were presence of RTR in 1 or both eyes and specific T. gondii IgG in blood serum samples. A minimum of 3 months with no signs of intraocular inflammation was required to differentiate chronic active retinochoroiditis from 2 consecutive episodes of RTR. The study included 112 nonimmunosuppressed patients with RTR. The patients completed a questionnaire including demographic data for the patient, as well as the first and last names and countries of origin of parents, grandparents, and great-grandparents. Informed consent was obtained from all participants and the study was approved by the human subjects review committee of Misiones Province. The patients were divided into 4 groups (Table): 1) patients reporting >1 ancestor born in Spain were considered Hispanic (n = 29); 2) patients without Hispanic ancestry who had >1 ancestor born in Poland, Ukraine, Russia, or Belarus, and who spoke Polish, Ukrainian, or Russian were considered Slavic (n = 28); 3) patients without Hispanic or Slavic ancestry who had >1 ancestor born in Germany or the Austro-Hungarian Empire and who spoke German were considered Germanic (n = 46); and 4) patients who did not fulfill the criteria of any of the above-mentioned groups were designated as others (n = 9). All patients had RTR at baseline; 28 had >1 more RTR episode during the follow-up period (Table). Multiple logistic regression analysis, in which Hispanic patients were used as a reference group, showed that Germanic and Slavic patients had a higher risk for reactivation during the follow-up period, but the odds ratio was significant only for Slavic patients after adjustment for rural dwelling. Table Demographic baseline characteristics of patients with reactivation of OT and multiple logistic regression analysis of the association between ethnic origin and risk for RTR during follow-up, Misiones province, Argentina, 2004–2014* More than 95% of Toxoplasma gondii strains in Europe belong to the clonal type II lineage, whereas strains from South America are genetically divergent and diverse (6,8). We hypothesize that the European population is poorly adapted to South American strains and therefore more susceptible to OT. If this hypothesis is true, Native Americans who had a long history of exposure to atypical strains from South America should be more resistant to OT. This hypothesis is reinforced by a recent survey conducted among Mbya-Guarani Indians, who had a serologic prevalence of toxoplasmosis 70%, but only 3.5% of them had toxoplasmic retinochoroidal lesions (M. Rudzinski, unpub. data). Argentineans have a large incidence of European genetic heritage in their Y-chromosomal and autosomal DNA, but ≈50% of their mitochondrial gene pool is of Native American ancestry (9). The amount of admixture between Europeans and Native Americans with inheritance of resistance genes to OT from Native Americans may explain the difference of susceptibility to RTR between Hispanic and non-Hispanic Europeans. Admixture events between Europeans and Native Americans mainly involved Hispanics whose migration to Argentina started in the 16th century and continued until the mid-20th century. Persons in Argentina who have Spanish surnames can carry as much as 80% Native American genetic ancestry (9,10). In contrast, the Slavic and German Europeans migrated to Misiones only during a large surge of European immigration between 1890 and 1950, and did not have substantial admixture with Native Americans. Despite the fact that this study was not a random or representative sample of all ethnic groups in Argentina and the Native American mixture of the patients was not known, and environmental and dietary influences were not examined, our results suggest host genetic factors as determinants of disease severity in OT.

Chronic Anterior Uveitis in Children

ABSTRACT Purpose: To describe the visual prognosis and remission rate of chronic anterior uveitis in pediatric patients. Methods: A retrospective case series of children with chronic anterior uveitis treated in the University of Buenos Aires. Juvenile idiopathic arthritis was defined according to the International League of Associations for Rheumatology criteria. Uveitis remission was defined according to SUN criteria. Results: There were 35 pediatric patients (61 eyes), mean age of uveitis onset was 7.69 ± 3 years, 60% were females and 74% had bilateral disease, median follow-up was 60 months (range: 12–192 months). JIA was more frequent in females (80.95 vs 21.43; p<0.0001) and oligoarthritis was the most common form. Remission rate was higher in males (HR = 4.99; 95% CI = 1.16–21.51; p = 0.031). More than 40 eyes remained with the same BCVA at 1 year of follow-up. Conclusions: Although remission was not common and only occurred after long-term follow-up, visual prognosis was good Received 30 August 2015; revised 6 March 2016; accepted 14 March 2016; published online 18 May 2016

Long-term Outcome of Lupus Nephritis Class II in Argentine Patients: An Open Retrospective Analysis.

BackgroundThere is controversy in medical literature over the outcome of patients with lupus nephritis (LN) class II. The aim of this study was to explore the risk of histological transformation (HT) and possible factors related to negative response to treatment in patients with mesangial LN class II. MethodsA retrospective and multicenter study was carried out that includes patients who had received a diagnosis of LN class II on their first renal biopsy. Creatinine, urine sediment, and proteinuria were recorded at the time of the first biopsy, 6 months, and 1, 2, and 5 years after the first biopsy. Response to treatment, HT, and long-term outcome were evaluated. ResultsForty-one patients were included. The manifestation at first biopsy was proteinuria greater than 0.5 g/d in 28 patients (68.29%; 8 [28.57%] of 28 patients had nephrotic syndrome), hematuria in 18 patients (43.90%), and deterioration of renal function in 3 patients (7.31%). During the follow-up (median, 8 years; range, 1–35 years), a new biopsy was performed in 18 patients (43.90%), and in 17 patients (17/18 [94.44%]), there was HT. Median time at rebiopsy was 32 months (range, 11–305 months). Of the 18 patients who had a second biopsy, 10 (55.55%) were on hydroxychloroquine versus 100% (19/19) of patients who did not undergo the procedure (P = 0.001). A year after the first renal biopsy, there are data available from 34 patients; of them, 24 patients (70.58%) had achieved response, and 10 patients (29.41%) had no response (NR) (missing data in 7). A higher 24-hour urinary protein at 6 months was predictor of worse outcome at 1 year, with statistical significance difference for the nonresponder group (median proteinuria, 2.3 g/d [range, 0–4.7 g/d]) compared with responders (median proteinuria, 0.28 g/d [range, 0–1.7 g/d]) (P = 0.0133).In the long-term follow-up (5 years), HT was the main cause of unfavorable outcome and was measured in 78.57% of patients (11/14 patients). ConclusionsThis series shows a high rate of HT in long-term follow-up. Proteinuria at 6 months made it possible to set aside patients who will have an unfavorable outcome in the long term and who will thus benefit from a more aggressive treatment. The results suggest that hydroxychloroquine had a nephroprotective effect.

Is reactivation of toxoplasmic retinochoroiditis associated to increased annual rainfall

Background: Reactivation of toxoplasmic retinochoroiditis is the most frequent form of uveitis in Misiones, Argentina. Fluctuations in the number of patients consulting with this type of uveitis were detected during the last decade. Since the province was consecutively exposed to rainy and dry periods over the last years, we decided to explore whether a relationship between reactivation of toxoplasmic retinochoroiditis and rain might be established according to the data registered during the 2004–2010 period. Results: The frequency of toxoplasmic reactivation episodes increases when precipitation increases (mostly in second and fourth trimesters of each year). Analysis of the independent variables demonstrates that precipitation is a significant predictor of the frequency of reactivation episodes. Although registered toxoplasmic reactivations were more frequent during the third trimester of the year, the association between the third trimester and the reactivation episodes did not reach statistical significance. Conclusion: Prolonged and intense rainfall periods were significantly associated with the reactivation of toxoplasmic retinochoroiditis. Changes promoted by this climatic condition on both the parasite survival in the soil as well as a putative effect on the host immune response due to other comorbidities are discussed.

Adalimumab Treatment in Patients with Vogt–Koyanagi–Harada Disease

ABSTRACT Purpose: To evaluate the clinical outcome and safety of adalimumab in patients with Vogt–Koyanagi–Harada (VKH) disease. Methods: VKH patients treated with adalimumab seen at the University of Buenos Aires were reviewed. Main outcome measures were visual acuity, anterior segment inflammation, optic nerve inflammation (ONI), steroid sparing effect, number of immunosuppressives, and relapses. Results: In total, 14 VKH patients, mean age 23.07 ± 8 years; median of adalimumab treatment 10 months, were analyzed. At start of adalimumab treatment (baseline), median of corticosteroid dose was 20 mg and at 6 months, 4 mg. At baseline, 11 patients were on immunosuppressive treatment and at 6 months only four continued with immunosuppressive therapy. In the 28 eyes, the median of active inflammation was 2 at baseline and 0 after 6 months on adalimumab. Conclusions: Treatment with adalimumab is an effective and safe option, reducing the need for oral corticosteroid and conventional immunosuppressive therapy.