Opportunistic tropical infections in immunosuppressed patients.

Autoimmune and autoinflammatory diseases are associated with severe morbidity, and represent an impactful health and economic burden worldwide. The treatment of these diseases can include a course with detrimental side effects. Immunosuppression increases the risk of opportunistic infections, but in some cases, the abrupt discontinuation of these medications can result in immune reconstitution inflammatory syndrome. Special attention must be directed to endemic tropical infections, such as leishmaniasis, Chagas disease, malaria, arbovirosis, yellow fever, leprosy, paracoccidioidomycosis, disseminated strongyloidiasis, and ectoparasitosis. These endemic diseases of developing countries can be considered as possible emerging diseases in developed regions partially because of environmental factors and migration. In the present article, we aim to review the evidence-based aspects of the most important opportunistic tropical infections in immunosuppressed patients. We also aim to review the important aspects of vaccination, chemical prophylaxis, and treatment for these infections in people with medication-induced immunosuppression.

Development of rheumatology training in Brazil: the option for a medical residency program.

OBJECTIVE: To describe the characteristics and progression of the supply of new rheumatologists in Brazil, from 2000 to 2015. METHODS: Consultations to databases and official documents of institutions related to training and certification of rheumatologists in Brazil took place. The data were compared, summarized and presented descriptively. RESULTS: From 2000 to 2015, Brazil qualified 1091 physicians as rheumatologists, of which 76.9% (n=839) completed a medical residency program in rheumatology (MRPR); the others (n=252) achieved this title without MRPR training. There was an expansion of MRPR positions. At the same time, there was a change in the profile of the newly qualified doctors. Early in the series, the fraction of new rheumatologists without MRPR, entering the market annually, was approaching 50%, dropping to about 15% in recent years. In 2015, Brazil offered 49 MRPR accredited programs, with 120 positions per year for access. There was an imbalance in the distribution of MRPR positions across the country, with a strong concentration in the southeast region, which in 2015 held 59.2% of the positions. Public institutions accounted for 94% (n=789) of graduates in MRPR during the study period, while still maintaining 93.3% (n=112) of seats for admission in 2015. CONCLUSIONS: In the last sixteen years, in parallel with the expansion of places of access, MRPR has established itself as the preferred route for rheumatology training in Brazil, mainly supported by public funds. Regional inequalities in the provision of MRPR positions still persist, as challenges that must be faced.

Vitamin d is related to gait recovery after total hip arthroplasty: A prospective analysis.

OBJECTIVES: To investigate the association between baseline serum levels of 25-hydroxyvitamin D (25(OH)D) and gait pattern in patients undergoing total hip arthroplasty (THA). METHODS: Prospective study of patients with hip osteoarthritis undergoing primary THA between January 2012 and December 2013. Blood samples were collected on the day of hospital admission. Gait analyses were performed before surgery and 3 months postoperatively. Internal moments were captured. RESULTS: Major improvements were observed in gait data after THA. 25(OH)D levels correlated with change in peak extension (R=0.25, p=0.017) and peak power generation (R=0.25, p=0.04). Multiple linear regression analyses were performed. In model 1, 25(OH)D and change in gait speed explained the variability of peak extension (R2=0.1, p=0.004). In model 2, only 25(OH)D explained the variability of peak power generation (R2=0.05, p=0.044). CONCLUSIONS: 25(OH)D levels were correlated with change in peak extension and peak power generation. The effect of 25(OH)D on change in gait variables after THA is modest.

The physician, the Emperor and the fibromyalgia: Charles-Édouard Brown-Séquard (1817-1894) and Dom Pedro II (1825-1891) of Brazil.

The physician Charles-Édouard Brown-Séquard was a neurologist of considerable importance. In 1846 his thesis 'Researches and Experiments on the Physiology of the Spinal Cord' brought out knowledge about the sensory pathways which remains until today. The Emperor, Dom Pedro II was the second and last Emperor of Brazil, reigning for 49 years and remembered for defending the nation's integrity, the end of slavery, support for education and culture, diplomacy and relations with international personalities. He married Dona Teresa Cristina of Bourbon-Two Sicilies (1822-1889) by proxy in 1843, the fourth and last Empress consort of Brazil. This paper reports the exchange of letters between these personalities of the XIX century. Although they lived far from each other and worked in areas so different, they discussed the health of the Empress in letters. Dom Pedro II made contact with Brown-Séquard hoping that ' … your knowledge shall help heal my wife of nervous disease … . ' According to Dom Pedro the Empress suffered ' … for a long time with more or less long interruptions of horrible neuralgic pains in the legs, head and the scalp. Two points on the dorsal spine feel the effects more or less with pressure applied … . ' In addition to describing and documenting the exchange of letters, this paper raises the possibility that the Empress suffered from the fibromyalgia syndrome.

Prospective evaluation of hypromellose 2% for punctal occlusion in patients with dry eye.

PURPOSE: The aim of this study was to evaluate the effectiveness of punctal occlusion using hypromellose 2% in patients with dry eye. METHODS: In this prospective, randomized single-blinded clinical trial, we evaluated 76 eyes of 38 patients (36 women and 2 men) with dry eye secondary to rheumatic diseases. In each patient, the lower lacrimal punctum of 1 eye was occluded using hypromellose 2%, whereas the contralateral eye underwent a simulation of the procedure (control group). Patients' eyes were assessed for burning, itching, redness, foreign body sensation, and tearing based on a visual scale questionnaire (score, 0-10). We also performed objective tests for evaluation of dry eye using a Schirmer test with anesthesia (basal tear secretion test), the tear film break-up time test, and fluorescein and rose bengal staining tests at 0, 28, and 56 days after treatment. RESULTS: Fluorescein and rose bengal staining tests showed that there was a significant reduction in signs after occlusion using hypromellose. The symptoms measured by the visual scale were significantly reduced. The values of the Schirmer test with anesthesia and the break-up time test increased significantly. The effects persisted for up to 8 weeks. There were no dropouts or reported side effects during the 24-month follow-up. CONCLUSIONS: Our results suggest that punctal occlusion using hypromellose 2% is a low-cost and safe additional treatment for dry eye.

Occurrence of Autoimmune Diseases Related to the Vaccine against Yellow Fever.

Yellow fever is an infectious disease, endemic in South America and Africa. This is a potentially serious illness, with lethality between 5 and 40% of cases. The most effective preventive vaccine is constituted by the attenuated virus strain 17D, developed in 1937. It is considered safe and effective, conferring protection in more than 90% in 10 years. Adverse effects are known as mild reactions (allergies, transaminases transient elevation, fever, headache) and severe (visceral and neurotropic disease related to vaccine). However, little is known about its potential to induce autoimmune responses. This systematic review aims to identify the occurrence of autoinflammatory diseases related to 17D vaccine administration. Six studies were identified describing 13 possible cases. The diseases were Guillain-Barré syndrome, multiple sclerosis, multiple points evanescent syndrome, acute disseminated encephalomyelitis, autoimmune hepatitis, and Kawasaki disease. The data suggest that 17D vaccination may play a role in the mechanism of loss of self-tolerance.

Haptoglobin and myeloperoxidase (- G463A) gene polymorphisms in Brazilian sickle cell patients with and without secondary iron overload.

We aimed to investigate the influence of haptoglobin (Hp) and myeloperoxidase (MPO - G463A; dbSNP rs2333227) gene polymorphisms on 78 sickle cell patients of a public hospital in the Federal District/Brazil with and without iron overload, to evaluate a possible association between these polymorphisms and clinical variability, response to treatment and prognosis. Data were obtained through laboratory tests, questionnaires, research in medical records and analyses of polymorphisms using PCR-based methods. Positive correlations were found between Hp and ferritin levels, hydroxyurea treatment, hospitalisation for and sequelae from stroke; and between MPO and number of hospitalizations in the past 12 months and splenectomy. Significant associations of specific Hp genotypes with comorbidities were also found, while results suggested that MPO AA homozygosis could increase effects of asplenia. Deviation from Hardy-Weinberg equilibrium, compatible with heterozygous deficit, was observed for Hp polymorphism. Odds ratio suggested the possibility that increased chance of hospitalisation for stroke (OR = 6.346; IC 95% = 1.56-25.79; p = 0.005) and sequelae of stroke (OR = 6.556; IC 95% = 1.578-27.237; p = 0.005) could be associated with lower frequency of 1S-2 than expected. In the interaction analyses, significant effects between subjects were shown only in the group without overload for Hp polymorphism in hs-CRP levels (p = 0.000) and number of transfusions (p = 0.018), and for MPO polymorphism (p = 0.000) and the interaction Hp/MPO (p = 0.000) in hs-CRP values. Results corroborate others indicating biological differences between Hp*1 alleles and highlight the importance of this study in understanding the biological significance of Hp and MPO polymorphisms in clinical variability and response to treatment of sickle cell patients.

The quality of life of patients with lupus erythematosus influences cardiovascular capacity in 6-minute walk test.

OBJECTIVE: To assess the association between quality of life and distance walked in the 6-minute walk test (6MWT) in Brazilian premenopausal patients with systemic lupus erythematosus (SLE) and compare their results with those of healthy controls. METHODS: Twenty-five premenopausal (18-45 years) patients diagnosed with low-activity SLE (mean SLEDAI: 1.52 ± 1.61) and 25 controls were matched for age, physical characteristics, and physical activity level (International Physical Activity Questionnaire/s-IPAQ). Both groups should not be involved in regular physical activity for at least six months before the study. The 6MWT distance (American Thoracic Society protocol), posttest heart rate (HRpost), posttest oxygen saturation (SpO2post) and the Borg scale of subjective perception of effort (SPE/CR10) were evaluated. The quality of life was assessed by use of the Short Form Health Survey 36 (SF-36). RESULTS: Patients with SLE had a significantly poorer quality of life, a shorter 6MWT distance (598 ± 45 m versus 642 ± 14 m, P < 0.001), and greater values of SPE/CR10 (6.28 ± 2.0 versus 5.12 ± 1.60, P< 0.05) and HRpost (134 ± 15 bpm versus 123 ± 23 bpm, P< 0.05) when compared with controls. The linear regression model suggested that quality of life was a significant predictor of 70% of the 6MWT distance. CONCLUSION: When compared with controls, patients with SLE walked a shorter distance in the 6MWT, which was associated with poorer quality of life.

Imaging diagnosis of early rheumatoid arthritis.

Early diagnosis of rheumatoid arthritis is essential for its proper management. Currently, the initial phase of rheumatoid arthritis is known to provide a window of therapeutic opportunity. Although the diagnosis is primarily clinical, the development and improvement of laboratory and imaging methods have contributed to earlier diagnosis and determination of procedures in early rheumatoid arthritis. In this article, the authors review the role of the major imaging methods used for assessing early rheumatoid arthritis, especially conventional radiography, ultrasonography, and magnetic resonance imaging.

Pierre-Auguste Renoir (1841-1919) and rheumatoid arthritis.

Pierre-Auguste Renoir (1841-1919), one of the world's most celebrated impressionist painters, suffered from rheumatoid arthritis for most of his life. His symptoms developed when he was in his 50s and they became aggressive at about the age of 60 years that led to almost complete disability when he was 70 years old. Although the deformities he suffered because of the rheumatoid arthritis were disabling, Renoir never stopped painting nor decreased the quality of his work. The transition between styles adopted by the painter (Impressionist, Dry and Pearly periods) bear no relationship to the stages of flare-ups or the establishment of joint deformities due to rheumatoid arthritis. His work shows aspects of the body's ability to overcome pain and physical limitation.

Risk of orthopedic surgical site infections in patients with rheumatoid arthritis treated with antitumor necrosis factor alfa therapy.

Introduction. International guidelines recommend interruption of anti-TNF medications in the perioperative period, but there are no randomized trials to support such recommendation. Objectives. To study literature evidence assessing the risk of surgical site infections in orthopedic surgery patients with RA using anti-TNF drugs, compared to untreated patients or those using conventional DMARD. Methods. Systematic review of cohort studies is concerning surgical site infections in orthopedic procedures in patients with RA. Results. Three studies were selected. Only one was considered of high-quality, albeit with low statistical power. The review resulted in inconclusive data, since the best quality study showed no significant differences between groups, while others showed increased risk of infections in patients using anti-TNF medications. Conclusion. It is unclear whether patients with RA using anti-TNF medications are at increased risk of surgical site infections. Randomized controlled trials or new high quality observational studies are needed to clarify the issue.

The presence of anti-citrullinated protein antibodies (ACPA) and rheumatoid factor on patients with rheumatoid arthritis (RA) does not interfere with the chance of clinical remission in a follow-up of 3 years.

Autoantibodies in early rheumatoid arthritis (RA) have important diagnostic value. The association between the presence of autoantibodies against cyclic citrullinated peptide and the response to treatment is controversial. To prospectively evaluate a cohort of patients with early rheumatoid arthritis (<12 months of symptoms) in order to determine the association between serological markers (rheumatoid factor (RF), anti-citrullinated protein antibodies) such as anti-cyclic citrullinated peptide antibodies (anti-CCP) and citrullinated anti-vimentin (anti-Sa) with the occurrence of clinical remission, forty patients diagnosed with early RA at the time of diagnosis were evaluated and followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, disease activity score 28 (DAS 28), as well as serology tests (ELISA) for RF (IgM, IgG, and IgA), anti-CCP (CCP2, CCP3, and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24, and 36 months of follow-up. The outcome evaluated was the percentage of patients with clinical remission, which was defined by DAS 28 lower than 2.6. Comparisons were made through the Student t test, mixed-effects regression analysis, and analysis of variance (significance level of 5%). The mean age was 45 years, and a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA-42%, RF IgG-30%, and RF IgM-50%), anti-CCP in 50% (no difference between CCP2, CCP3, and CCP3.1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence and anti-CCP was observed, but the anti-Sa increased to 17.5% (P = 0.001). The percentage of patients in remission, low, moderate, and intense disease activity, according to the DAS 28, was of 0, 0, 7.5, and 92.5% (initial evaluation) and 22.5, 7.5, 32.5, and 37.5% (after 3 years). There were no associations of the presence of autoantibodies in baseline evaluation and in serial analysis with the percentage of clinical remission during follow-up of 3 years The presence of autoantibodies in early RA has no predictive value for clinical remission in early RA.

Baseline HAQ and SF-36 questionnaire scores cannot predict clinical remission, radiographic progression or the need for biological therapy in a three-year prospective study of a Brazilian early rheumatoid arthritis cohort.

This study evaluates prospectively whether baseline scores [Health Assessment Questionnaire (HAQ) and SF-36] can predict clinical and radiographic evolution in a cohort of early rheumatoid arthritis (RA) during a 3-year follow-up. Forty consecutive early RA patients were followed for 3 years, while receiving standardized treatment according to a pre-established protocol. HAQ and SF-36 were administered at the initial evaluation and at 3, 6, 12, 18, 24 and 36 months. Hands and feet radiographs were obtained at the initial evaluation and at 12, 24 and 36 months. Preselected outcomes were the occurrence of radiographic erosions, the achievement of an EULAR remission, low disease activity status and the need for biological therapy. The mean age at onset was 45 years with a 90% female predominance. Erosions were found in 42% of patients at T0 and in 70% after 3 years (P < 0.001). At T0, the proportion of patients in remission, low, moderate or high disease activity was 0, 0, 7.5 and 92.5% and 22.5, 7.5, 32.5 and 37.5%, respectively, at 3 years. The mean baseline HAQ score was 1.89 and 0.77 by the third year (P < 0.0001). Most SF-36 domains showed significant improvement except for general state and vitality. Biological therapy was deemed necessary in 22.5% of patients. The initial HAQ and SF-36 scores were not associated with clinical remission, bone erosions or the need for biological therapy at 36 months. The HAQ and SF-36 scores measured at baseline could not predict at 3 years, the preselected outcomes in a Brazilian cohort.

Head Up Tilt Testing: An Appraisal of Its Current Role in the Management of Patients with Syncope.

Head up tilt testing (HTT) is now commonly used to investigate otherwise unexplained syncope and presyncope. This test has been used for over 20 years primarily to diagnose neurally mediated syncope, but HTT's exact role in the diagnostic process remains uncertain. Recognized limitations include poor reproducibility, lack of prognostic role, and insufficient randomized studies to guide therapeutic choice. In this review, we describe the indications and methods recommended by present guidelines on utilizing HTT. In addition, present criticisms and limitations of this test, along with future perspectives, are outlined.

Prospective evaluation of the quality of life in a cohort of patients with early rheumatoid arthritis.

INTRODUCTION: Few studies have prospectively assessed the tools used to measure quality of life, both generic and specific, in patients with early rheumatoid arthritis (RA). OBJECTIVE: The objective of this study was to characterize a population of patients with early RA (less than 12 months after symptom onset at the time of the diagnosis) prospectively followed for the pattern of responses to questionnaires addressing quality of life, the Health Assessment Questionnaire (HAQ) and Medical Outcomes Study SF-36 Health Survey (SF-36). PATIENTS AND METHODS: Forty patients with early RA at the time of diagnosis, treated with a standard treatment regimen, were prospectively followed for 3 years. Demographic and clinical data were recorded, and HAQ and SF-36 questionnaires were applied at baseline and after 3, 6, 12, 18, 24, and 36 months. Paired Student t test and Wilcoxon test were used for comparisons (significance level of 5%). RESULTS: The mean age was 45 years, with a prevalence of the female gender (90%). The average score of the initial HAQ was 1.89, with a progressive decline to 0.77 in the third year (P < 0.0001). Most domains of the SF-36 questionnaire presented significant improvement during the three years of follow-up, except for general health and vitality. CONCLUSION: In this population of patients with early RA at the time of diagnosis, the results showed significant impact on quality of life at the time of diagnosis, as measured by HAQ and SF-36 questionnaires. The early treatment of RA seems to be associated with improved health-related quality of life reported by patients.

Demographic and clinical characteristics of a cohort of patients with early rheumatoid arthritis.

INTRODUCTION: Very few studies carried out with Latin American populations on the demographic and clinical characteristics of patients diagnosed with early rheumatoid arthritis (RA) can be found in the literature. OBJECTIVE: To characterize a population of patients with early RA, prospectively followed, concerning demographic and clinical aspects and compare them with other similar cohorts. PATIENTS AND METHODS: The data presented are part of an incident cohort prospective study, in which 65 patients with early RA were evaluated and followed regularly for 36 months at the Early Rheumatoid Arthritis Outpatient Clinic of the University Hospital of Brasília (HUB, from the Portuguese). The demographic and clinical data of the initial evaluation, including general characteristics, clinical history, and physical examination were recorded. Descriptive statistics of the variables was applied. RESULTS: Women (86%) with a mean age of 45.6 years, Caucasian or Black (47.6%), belonging to intermediate-low social classes (53.85%), with 8.3 years of schooling, predominated. The presenting symptoms of the majority of patients were acute (76.9%), with polyarticular onset (69.2%), persistent synovitis of the hands (90.7%), and prolonged morning stiffness (157 minutes on average). Patients had a high average score of painful (18.6) and swollen (13.9) joints and high prevalence of rheumatoid nodules (15.3%), which suggests disease with aggressive presentation in its initial phases. CONCLUSION: The demographic and clinical characteristics of patients enrolled in this Brazilian cohort differed, on several aspects, from previously published North American, European, and Latin American cohorts.

Laboratory characteristics of a cohort of patients with early rheumatoid arthritis.

INTRODUCTION/OBJECTIVE: To characterize a population of patients with early rheumatoid arthritis (RA) according to laboratory aspects, comparing it with other similar cohorts. METHODS: Data presented are part of a prospective incident cohort study that evaluated 65 patients with early RA, followed for 36 months from the diagnosis at Early Rheumatoid Arthritis Clinic of Hospital Universitário de Brasília (HUB). We recorded demographics, clinical, and laboratory data relevant to the cohort initial assessment, including red blood cells, evidence of inflammatory activity, and presence of autoantibodies (rheumatoid factor (RF)), cyclic citrullinated peptide antibodies (anti-CCP), and antivimentin citrullinated (anti-Sa). RESULTS: There was a preponderance of female (86%) with mean age of 45.6 years. Twelve patients (18.46%) had laboratory diagnosis of anemia (hemoglobin < 12 g / dL). Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were above the reference value for 51 (78.46%) and 46 (70.76%) patients, respectively. Thirty-two patients (49.23%) were positive for at least one of the RF isotypes, and 28 patients (43.07%) were positive for IgA RF, 19 (29.23%) for IgG, and 32 ( 49.23%) for IgM RF, respectively; 34 patients (52.30%) were positive for at least one of the techniques used in investigation of anti-CCP (CCP2, or CCP3, or CCP3.1), while 9 (13,85%) were positive for anti-Sa. CONCLUSIONS: The laboratory characteristics of patients enrolled in this Brazilian cohort are similar in many respects to those of North-American, European, and Latin-American cohorts previously published.

Prognostic evaluation of early rheumatoid arthritis.

The progression of rheumatoid arthritis (RA) is quite variable, ranging from very mild or subclinical forms (approx. 10%) to rapidly progressing and debilitating forms (10-15%). The majority of patients present with an intermediate stage with episodes of exacerbation separated by periods of relative inactivity, which evolves to progressive functional losses. To optimise the therapeutic management of early RA it is necessary to perform periodic evaluations of the clinical and laboratory test responses to the treatment instituted, as well as the parameters indicating disease prognosis. Composite measures are frequently used to evaluate the disease activity score (DAS), including the response criteria of the American College of Rheumatology (ACR), the response criteria and the DAS according to the European League Against Rheumatism (EULAR) and the composite indices of disease activity (CIDsA): DAS, the index of disease activity based on 28 joints (DAS 28), the simplified disease activity index (SDAI) and the clinical disease activity index (CDAI). The evaluation of prognosis includes investigation of the absence or occurrence of disease and joint damage remission. Due to the multifaceted nature of RA, no single clinical or laboratory parameter is able to describe satisfactorily the level of inflammatory activity or the disease prognosis at any given time.

[Autoantibodies as predictors of biological therapy for early rheumatoid arthritis]. / Autoanticorpos como preditores da necessidade de terapia biológica na artrite reumatóide inicial.

INTRODUCTION: The association between serological markers with the need of biological therapy for early rheumatoid arthritis (ERA) is not known, with few available data addressing this question. OBJECTIVES: To prospectively evaluate a cohort of patients with ERA (less than 12 months of symptoms) in order to determine the possible association between serological markers (rheumatoid factor (RF), anti-cyclic citrullinated peptide antibodies (anti-CCP), and citrullinated anti-vimentin (anti-Sa) with parameters of therapeutic outcome (this later defined by the need of introducing biological therapy). PATIENTS AND METHODS: Forty patients with early RA were evaluated at the time of diagnosis and have been followed for 3 years, in use of standardized therapeutic treatment. Demographic and clinical data were recorded, as well as serology tests (ELISA) for RF (IgM, IgG and IgA), anti-CCP (CCP2, CCP3 and CCP3.1) and anti-Sa in the initial evaluation and at 3, 6, 12, 18, 24 and 36 months of follow-up. As outcomes of the RA development, the need or not for biological therapy during the follow-up period were considered. Comparisons were made through the Student t test, mixed-effects regression analysis and analysis of variance (significance level of 5%). RESULTS: The mean age was 45 (+/- 12) years; a female predominance was observed (90%). At the time of diagnosis, RF was observed in 50% of cases (RF IgA - 42%, RF IgG - 30% and RF IgM - 50%), anti-CCP in 50% (no difference between CCP2, CCP3 and CCP3. 1) and anti-Sa in 10%. After 3 years, no change in the RF prevalence neither in the anti-CCP was observed, but the anti-Sa increased to 17.5% (p = 0.001). Biological therapy was necessary in 22.5% of patients. The mean RF IgA and anti-CCP 2 levels during the 3 years were higher among patients who needed biological therapy (p <0.05 for both). CONCLUSION: Higher titles of RF and anti-CCP over time were associated with the need for biological therapy.