Objective: To determine the frequency of and the factors related to delayed diagnosis of sarcoidosis in Brazil. Methods: We evaluated patients with a biopsy-proven diagnosis of sarcoidosis, using a questionnaire that addressed the following: time since symptom onset and since the first medical visit; and the number and specialty of the physicians visited. We divided the patients by the timeliness of the diagnosis-timely (< 6 months) and delayed ( 6 months)-comparing the two groups in terms of systemic and pulmonary symptoms; extrathoracic involvement; spirometric data; radiological staging; level of education; income; and tuberculosis (diagnosis and treatment). Results: We evaluated 100 patients. The median number of physicians consulted was 3 (range, 1-14). In 11 cases, sarcoidosis was diagnosed at the first visit. In 54, the first physician seen was a general practitioner. The diagnosis of sarcoidosis was timely in 41 patients and delayed in 59. The groups did not differ in terms of gender; race; type of health insurance; level of education; income; respiratory/systemic symptoms; extrathoracic involvement; and radiological staging. In the delayed diagnosis group, FVC was lower (80.3 ± 20.4% vs. 90.5 ± 17.1%; p = 0.010), as was FEV1 (77.3 ± 19.9% vs. 86.4 ± 19.5%; p = 0.024), misdiagnosis with and treatment for tuberculosis ( 3 months) also being more common (24% vs. 7%, p = 0.032, and 20% vs. 0%; p = 0.002, respectively). Conclusions: The diagnosis of sarcoidosis is often delayed, even when the imaging is suggestive of sarcoidosis. Delayed diagnosis is associated with impaired lung function at the time of diagnosis. Many sarcoidosis patients are misdiagnosed with and treated for tuberculosis.

Keywords: Sarcoidosis; Sarcoidosis, pulmonary/diagnosis; Tuberculosis.

Objective: To estimate the total time elapsed between symptom onset and diagnosis of pulmonary tuberculosis (patient delay plus health care system delay), analyzing the factors associated with delayed diagnosis in the state of Rio de Janeiro, Brazil. Methods: We conducted a questionnaire-based survey involving 218 pulmonary tuberculosis patients treated for two months at 20 health care clinics and 3 hospitals in eight cities within the state of Rio de Janeiro. We collected socioeconomic and demographic data, as well as data regarding the health care system and the medical history of the patients. Results: The median time elapsed from the onset of symptoms to diagnosis was 68 days (interquartile range [IQR]: 35-119 days). The median patient delay (time from symptom onset to initial medical visit) was 30 days (IQR: 15-60 days), and the median health care system delay (time from initial medical visit to diagnosis) was 21 days (IQR: 8-47 days). A cut-off point of 21 days was adopted. The factors independently associated with patient delay were female gender, cough, and unemployment [adjusted OR (95% CI) = 2.7 (1.3-5.6); 11.6 (2.3-58.8); and 2.0 (1.0-3.8), respectively], whereas only female gender was independently associated with health care system delay (OR= 3.2; 95% CI: 1.7-6.0). Conclusions: Delayed diagnosis of pulmonary tuberculosis remains a problem in Rio de Janeiro, increasing the risk of transmission and mortality, that risk being greater for women and the socioeconomically disadvantaged. Patients might not recognize the significance of chronic cough as a health problem. Tuberculosis education programs targeting women might improve this situation.

Keywords: Lung neoplasms; Neoplasm metastasis; Antineoplastic combined chemotherapy protocols; Radiotherapy, computer-assisted.

Objective: To identify predictive features associated with the course of sarcoidosis at initial evaluation and to develop a predictive score. Methods: This was a retrospective study involving pulmonary sarcoidosis patients, classified as having a self-limited or persistent course of disease, comparing data between the outcomes by univariate analysis. Features related to persistent disease were selected by multivariate analysis and a prognostic score was designed. Results: The sample comprised 200 patients (mean age = 49 years). The median duration of symptoms to diagnosis was 12 months, and delayed diagnosis (> 12 months) was found in 43% of the cases. The most common radiological stage was II; 37% had reduced FVC. Relevant systemic involvement was detected in 37% of the patients. Treatment for tuberculosis was prescribed in 44 patients prior to sarcoidosis diagnosis. Treatment for sarcoidosis was required in 77% of the sample, and the disease course was persistent in 115 cases. Excluding 40 patients with fibrotic disease, prognostic factors to persistent disease were parenchymal involvement, delayed diagnosis, dyspnea, relevant systemic involvement, and reduced FVC. On the basis of the analysis, a 3-letter scoring system (A, B and C) was developed according to the selected factors. The positive predictive values for persistent course for A (= 1 point) and C scores (= 4 points) were 12.5% and 81.8%, respectively. Conclusions: A score can be derived by selected features at initial evaluation, allowing the prediction of outcomes in a significant number of sarcoidosis patients.

Keywords: Sarcoidosis; Prognosis; Chronic disease; Tuberculosis.

Objective: This case study, conducted in the state of Rio Grande do Sul (RS), Brazil, aims to determine the local profile of sarcoidosis, describing patient characteristics, clinical presentation and pulmonary function, as well as analyzing the results of radiological, histopathological and biochemical tests, at the time of diagnosis in a series of sarcoidosis patients. Methods: A retrospective study of 92 patients with sarcoidosis treated on the Pavilhão Pereira Filho (Pereira Filho [Respiratory Diseases] Ward) of the Hospital Santa Casa, in the city of Porto Alegre, RS, between 1990 and 2003. The protocol included the collection of clinical, biochemical, radiological, spirometric and histological data. Results: There was no significant gender-based difference in frequency (men, 42%; women, 58%). Mean age was 41.8 ± 14.1 years, with 87% of patients being between 20 and 60 years old. Caucasians predominated (84%). Most patients (61%) had never smoked, 29% were former smokers, and 10% were current smokers. The majority (33%) of the diagnoses were made in winter. Among the clinical findings, it is of note that 12% were asymptomatic, 18% presented pulmonary symptoms only, 22% presented extrapulmonary symptoms only, and 48% presented pulmonary and extrapulmonary symptoms. Spirometry was performed in 79% of patients at the time of diagnosis. In 45% of those patients, abnormal results were obtained: a restrictive pattern was seen in 23%, an obstructive pattern in 18% and a mixed pattern in 4%. Classification by radiological type revealed that 30% were stage I, 48% were stage II, and 22% were stage III. Conclusion: The findings of this study are quite similar to those of other studies in the literature, particularly those conducted in Europe.

Keywords: Sarcoidosis, pulmonary/diagnosis; Sarcoidosis, pulmonary/pathology; Lung diseases/pathology; Prognosis; Retrospective studies

Objective: To analyze the epidemiological characteristics of sarcoidosis patients in the city of Rio de Janeiro, Brazil. Methods: A descriptive, case-control study involving 100 sarcoidosis patients under outpatient treatment between 2008 and 2010 at the Pedro Ernesto University Hospital, located in the city of Rio de Janeiro, Brazil. The diagnosis of sarcoidosis was based on clinical, radiological, biochemical, and histopathological criteria. Results: There was a predominance of females in the 35-40 year age bracket (range, 7-69 years), who accounted for 65% of the sample, although there was a second peak at approximately 55 years of age. The most common symptom was dyspnea (in 47%), and the most common radiological findings were pulmonary and lymph node involvement (stage II; in 43%), followed by stage III (in 20%), stage I (in 19%), stage 0 (in 15%), and stage IV (in 3%). No pleural effusion or digital clubbing was observed at diagnosis. The tuberculin skin test was negative in 94 patients. Spirometric findings at diagnosis were normal in 61 patients; indicative of obstructive lung disease in 21; and indicative of restrictive lung disease in 18. The most common biopsy sites were the lungs (principally by bronchoscopy) and the skin, the diagnosis being confirmed by biopsy in 56% and 29% of the cases, respectively. Treatment with prednisone was initiated in 75% of the patients and maintained for more than 2 years in 19.7%. Conclusions: This study corroborates the findings of previous studies regarding the epidemiological characteristics of sarcoidosis patients.

Keywords: Sarcoidosis/epidemiology; Sarcoidosis/diagnosis; Sarcoidosis/therapy.

Sarcoidosis is a multisystem inflammatory disorder of unknown cause. It most commonly affects the pulmonary system but can also affect the musculoskeletal system, albeit less frequently. In patients with sarcoidosis, rheumatic involvement is polymorphic. It can be the presenting symptom of the disease or can appear during its progression. Articular involvement is dominated by nonspecific arthralgia, polyarthritis, and Löfgren's syndrome, which is defined as the presence of lung adenopathy, arthralgia (or arthritis), and erythema nodosum. Skeletal manifestations, especially dactylitis, appear mainly as complications of chronic, multiorgan sarcoidosis. Muscle involvement in sarcoidosis is rare and usually asymptomatic. The diagnosis of rheumatic sarcoidosis is based on X-ray findings and magnetic resonance imaging findings, although the definitive diagnosis is made by anatomopathological study of biopsy samples. Musculoskeletal involvement in sarcoidosis is generally relieved with nonsteroidal anti-inflammatory drugs or corticosteroids. In corticosteroid-resistant or -dependent forms of the disease, immunosuppressive therapy, such as treatment with methotrexate or anti-TNF-, is employed. The aim of this review was to present an overview of the various types of osteoarticular and muscle involvement in sarcoidosis, focusing on their diagnosis and management.

Keywords: Sarcoidosis; Joints; Muscles; Bone and Bones.

Pulmonary cavitation is rather uncommon in patients with sarcoidosis, and aspergilloma is even more uncommon in such cases. Here, we present the case of a 63-year-old female patient with cavitary lung disease who had been under treatment for TB for 9 months. A diagnosis of pulmonary sarcoidosis was established based on the fiberoptic bronchoscopy finding of noncaseating granuloma. Treatment with corticosteroids led to a dramatic improvement in symptoms. While under treatment for sarcoidosis, the patient developed an aspergilloma. She presented immediate skin test reactivity to Aspergillus fumigatus, as well as positivity for A. fumigatus serum precipitins. This is the first reported case of aspergilloma formation in a patient with cavitary sarcoidosis in India.

Keywords: Sarcoidosis, pulmonary; Aspergillosis; Medical records.

Objective: The aim of this study was to use a Serbian-language version of the disease-specific, self-report Sarcoidosis Health Questionnaire (SHQ), which was designed and originally validated in the United States, to assess health status in sarcoidosis patients in Serbia, as well as validating the instrument for use in the country. Methods: This was a cross-sectional study of 346 patients with biopsy-confirmed sarcoidosis. To evaluate the health status of the patients, we used the SHQ, which was translated into Serbian for the purposes of this study. We compared SHQ scores by patient gender and age, as well as by disease duration and treatment. Lower SHQ scores indicate poorer health status. Results: The SHQ scores demonstrated differences in health status among subgroups of the sarcoidosis patients evaluated. Health status was found to be significantly poorer among female patients and older patients, as well as among those with chronic sarcoidosis or extrapulmonary manifestations of the disease. Monotherapy with methotrexate was found to be associated with better health status than was monotherapy with prednisone or combination therapy with prednisone and methotrexate. Conclusions: The SHQ is a reliable, disease-specific, self-report instrument. Although originally designed for use in the United States, the SHQ could be a useful tool for the assessment of health status in various non-English-speaking populations of sarcoidosis patients.

Keywords: Sarcoidosis; Health status; Validation studies; Questionnaires; Self report; Serbia.

Objective: To evaluate the quality of diagnosis and the epidemiological profile of patients with pleural tuberculosis in the state of Roraima, Brazil, in order to provide technical support for the development and implementation of public policies to combat the disease. Methods: This was a cross-sectional study designed to determine the prevalence of pleural forms of tuberculosis in Roraima between 2005 and 2013 and to evaluate the diagnostic criteria used, as well as their determinants. This study was based on secondary data from the Brazilian Case Registry Database, including all reported cases of pleural tuberculosis in the state during the study period. Diagnoses based on bacteriological or histopathological confirmation were defined as high-quality diagnoses. Results: Among the 1,395 cases of tuberculosis reported during the study period, 116 (8.3%) were cases of pleural tuberculosis, accounting for 38.9% of all cases of extrapulmonary tuberculosis in the sample. The incidence rate of pleural tuberculosis did not follow the downward trend observed for the pulmonary form of the disease during the same period. The prevalence of cases with a high-quality diagnosis was 28.5% (95% CI: 20.4-37.6%). In a univariate analysis, none of the demographic or clinical characteristics collected from the database were found to have a significant impact on the outcome (as explanatory variables). Conclusions: The quality of the diagnoses in our study sample was considered unsatisfactory. Limited access to specific diagnostic methods might have contributed to these results.

Keywords: Tuberculosis/diagnosis; Tuberculosis/epidemiology; Tuberculosis, pleural.

Objective: To compare the frequency of unfavorable outcome (death or default and treatment failure) between tuberculosis (TB)/HIV co-infected patients treated for TB after laboratory confirmation of the diagnosis and TB/HIV co-infected patients who were so treated without diagnostic confirmation. Methods: A retrospective cohort of TB/HIV co-infected patients who started TB treatment between July of 2002 and June of 2004 at an HIV/AIDS referral center in Recife, Brazil. The main exposure variable, laboratory confirmation of TB, was adjusted for three different sets of variables: sociodemographic variables; HIV/AIDS-related variables; and TB-related variables. In order to evaluate the statistical significance of the results, we calculated odds ratios, with 95% confidence intervals, and p values (from chi-square tests and likelihood ratio tests). Results: A total of 262 patients were studied. No association was found between laboratory confirmation of the diagnosis of TB at treatment outset and unfavorable outcome, even after adjustment for confounders. In the final multiple logistic regression model, the following variables remained: the presence of other opportunistic diseases; CD4 lymphocyte count below 50 cells/mm3; viral load between 10,000 and 100,000 copies/mL; dyspnea; the disseminated form of TB; and change in the TB treatment regimen due to adverse reactions or intolerance. Conclusions: Our results suggest that TB treatment in TB/HIV co-infected patients without etiologic confirmation of TB, at the discretion of experienced physicians in referral centers, did not increase the risk of unfavorable outcomes. In addition, it allowed the identification of groups that should be closely monitored due to a greater risk of unfavorable outcomes.

Keywords: Tuberculosis; Diagnosis; Therapeutics; Treatment outcome; HIV infections.

Alpha-1 antitrypsin deficiency (AATD) is a rare genetic disorder caused by a mutation in the SERPINA1 gene, which encodes the protease inhibitor alpha-1 antitrypsin (AAT). Severe AATD predisposes individuals to COPD and liver disease. Early diagnosis is essential for implementing preventive measures and limiting the disease burden. Although national and international guidelines for the diagnosis and management of AATD have been available for 20 years, more than 85% of cases go undiagnosed and therefore untreated. In Brazil, reasons for the underdiagnosis of AATD include a lack of awareness of the condition among physicians, a racially diverse population, serum AAT levels being assessed in a limited number of individuals, and lack of convenient diagnostic tools. The diagnosis of AATD is based on laboratory test results. The standard diagnostic approach involves the assessment of serum AAT levels, followed by phenotyping, genotyping, gene sequencing, or combinations of those, to detect the specific mutation. Over the past 10 years, new techniques have been developed, offering a rapid, minimally invasive, reliable alternative to traditional testing methods. One such test available in Brazil is the A1AT Genotyping Test, which simultaneously analyzes the 14 most prevalent AATD mutations, using DNA extracted from a buccal swab or dried blood spot. Such advances may contribute to overcoming the problem of underdiagnosis in Brazil and elsewhere, as well as being likely to increase the rate detection of AATD and therefore mitigate the harmful effects of delayed diagnosis.

Keywords: alpha 1-antitrypsin deficiency/diagnosis; alpha 1-antitrypsin deficiency/genetics; Genotyping techniques.

Background: Various primers are being tested for the detection of Mycobacterium tuberculosis DNA. The accuracy of the polymerase chain reaction (PCR) depends on the target sequence used and whether the test will be performed in culture or in clinical specimens. Objectives: To identify DNA sequences, specifically those commonly reported as targets for diagnosis of tuberculosis (TB), in clinical samples of M. tuberculosis strains. Method: Eighty-one clinical samples from suspected TB patients were initially processed and submitted to bacilloscopy (smear) and culture, and PCR was performed with specific primers for the following targets: IS 6110, 65 kDa, 38 kDa and MPB64. Results: Smear and culture results were negative in 24 samples, as was the PCR. The 19 samples testing smear positive, as well as the isolated strains, were 100% positive on PCR, with the exception of the 89.4% result from PCR with MPB64 primers. In the 38 smear negative and culture positive samples, PCR results were inconsistent. The primers specific for amplifying the 123 bp IS 6110 fragment gave the highest positivity (92.1%), diagnostic agreement (0.9143), co-positivity (94.7%) and co-negativity (100%). Conclusion: The IS 6110, 38 kDa, MPB64 and 65 kDa sequences were found in the genome of all M. tuberculosis strains isolated in patients from the state of Amazonas. The protocol for processing the clinical samples prior to PCR analysis and the specific primers used to amplify the 123bp IS 6110 fragment showed a greater efficiency in diagnosing pulmonary (paucibacillary) tuberculosis in comparison to published data.

Keywords: Primers/PCR. Diagnosis/Tuberculosis. Mycobacterium tuberculosis.

Objective: To determine the diagnostic yield of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in non-neoplastic patients with isolated intrathoracic lymphadenopathy (IL). Methods: This was a retrospective study of patients with isolated IL referred for EBUS-TBNA. We calculated the sensitivity, specificity, accuracy, positive predictive value (PPV), and negative predictive value (NPV) of EBUS-TBNA in the diagnosis of granulomatous, reactive, and neoplastic lymphadenopathy. In cases of nonspecific granulomas, reactive lymphadenopathy, or inconclusive results, a definitive diagnosis was established by other diagnostic procedures or during a follow-up period of at least 18 months. Results: Among the 58 patients included in the study, EBUS-TBNA established a diagnosis of granulomatous disease in 22 (38%), reactive lymphadenopathy in 15 (26%), cancer in 8 (14%), and other diseases in 3 (5%). Results were inconclusive in 10 (17%), the diagnosis being established by other bronchoscopic procedures in 2 (20%) and by surgical procedures in 8 (80%). A final diagnosis of reactive lymphadenopathy was established in 12. Of those, 11 (92%) had their diagnosis confirmed during follow-up and 1 (8%) had their diagnosis confirmed by mediastinoscopy. In another 3, a final diagnosis of sarcoidosis or neoplasm was established. For the diagnosis of granulomatous disease, neoplasms, and reactive lymphadenopathy, EBUS-TBNA was found to have a sensitivity of 73%, 68%, and 92%, respectively; a specificity of 100%, 100%, and 93%, respectively; an accuracy of 86%, 93%, and 93%, respectively; a PPV of 100%, 100%, and 80%, respectively; and an NPV of 78%, 92%, and 98%, respectively. Conclusions: In non-neoplastic patients, granulomatous disease and reactive lymphadenopathy appear to be common causes of isolated IL. EBUS-TBNA shows promising results as a first-line minimally invasive diagnostic procedure. The results obtained by EBUS-TBNA can be optimized by examining clinical and radiological findings during follow-up or by comparison with the results obtained with other bronchoscopic methods.

Keywords: Endoscopic ultrasound-guided fine needle aspiration; Lymphadenopathy/diagnosis; Neoplasms.

Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a new method for the diagnosis and staging of mediastinal lymph nodes. The objective of this study was to evaluate the preliminary results obtained with EBUS-TBNA in the diagnosis of lesions and mediastinal lymph node staging. Methods: We evaluated patients with tumors or mediastinal adenopathy, diagnosed with or suspected of having lung cancer. The procedures were performed with the patients under sedation or under general anesthesia. Material was collected by EBUS-TBNA, after which it was prepared on slides, fixed in either absolute alcohol (for cytology) or formalin (for cell-block analysis). Results: We included 50 patients (30 males). The mean age was 58.3 ± 13.5 years. We performed 201 biopsies of 81 lymph nodes or mediastinal masses (mean of 2.5 punctures/biopsy). The quantity of material was considered sufficient for cytology in 37 patients (74%), 21 (57%) of whom were thus diagnosed with malignancy. Of the remaining 16 patients, 1 was diagnosed with tuberculosis, 6 entered clinical follow-up, and 9  underwent further investigation (2 diagnosed with neoplasm-false-negative results). The yield was higher when the procedure was performed for diagnostic purposes, as well as being higher in patients with lesions in multiple stations and in biopsies involving the subcarinal lymph node station. One patient had endobronchial bleeding, which was resolved with local measures. There were no deaths among the patients evaluated. Conclusions: This preliminary experience shows that EBUS-TBNA is a safe procedure. Our diagnostic yield, although lower than that reported in the literature, was consistent with the learning curve for the method.

Keywords: Ultrasonography, interventional; Biopsy, fine-needle; Neoplasm staging; Lung neoplasms; Bronchoscopy.