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.

Background: Pulmonary involvement is common in leptospirosis and usually characterized by hemoptysis, dyspnea and diffuse bilateral infiltrates in chest X-rays. Such findings may be compatible with alveolar hemorrhage, already described by some authors both in autopsies and bronchoalveolar lavage (BAL). Objective: To evaluate the presence of alveolar hemorrhage, diagnosed through BAL, in bearers of leptospirosis patients with pulmonary involvement emphasizing the method's importance for early detection of this complication. Method: Seven patients with leptospirosis were submitted to BAL. All presented respiratory symptoms and/or infiltrates in the chest X-rays and/or hypoxemia. Alveolar hemorrhage was defined by the following findings in BAL: percentage of siderophages e"20% and/or Golde score >100 and/or hemorrhagic fluid. Culture and direct tests for leptospirosis were performed in BAL. Diagnosis of disease was confirmed by microscopy serum agglutination. Results: The aspect of the bronchoscopy was normal in five patients, showed blood in the bronchial tree in one case and inflammatory manifestations in another. The BAL aspect was hemorrhagic for all patients portraying alveolar hemorrhage. Culture and direct tests were negative for Leptospiras in the BAL. Conclusions: Leptospirosis must be taken into account in the differential diagnosis of alveolar hemorrhage. The BAL was confirmed as an efficient method for detection of alveolar hemorrhage in leptospirosis, to recommend immediate therapy for the purpose of preventing its evolution to massive hemoptysis and respiratory failure.

Keywords: Leptospirosis. Bronchoalveolar lavage fluid. Radiography, thoracic.

Objective: To determine whether simple diagnostic methods can yield relevant disease information in patients with rheumatoid arthritis (RA). Methods: Patients with RA were randomly selected for inclusion in a cross-sectional study involving clinical evaluation of pulmonary function, including pulse oximetry (determination of SpO2, at rest), chest X-ray, and spirometry. Results: A total of 246 RA patients underwent complete assessments. Half of the patients in our sample reported a history of smoking. Spirometry was abnormal in 30% of the patients; the chest X-ray was abnormal in 45%; and the SpO2 was abnormal in 13%. Normal chest X-ray, spirometry, and SpO2 were observed simultaneously in only 41% of the RA patients. A history of smoking was associated with abnormal spirometry findings, including evidence of obstructive or restrictive lung disease, and with abnormal chest X-ray findings, as well as with an interstitial pattern on the chest X-ray. Comparing the patients in whom all test results were normal (n = 101) with those in whom abnormal test results were obtained (n = 145), we found a statistically significant difference between the two groups, in terms of age and smoking status. Notably, there were signs of airway disease in nearly half of the patients with minimal or no history of tobacco smoke exposure. Conclusions: Pulmonary involvement in RA can be identified through the use of a combination of diagnostic methods that are simple, safe, and inexpensive. Our results lead us to suggest that RA patients with signs of lung involvement should be screened for lung abnormalities, even if presenting with no respiratory symptoms.

Keywords: Arthritis, rheumatoid; Lung diseases, interstitial; Spirometry; Radiography, thoracic; Airway ob-struction.

A 27-year-old male patient presented with respiratory symptoms, bilateral enlargement of the cervical lymph nodes and enlarged liver. In the imaging studies, bilateral enlargement of the hilar nodes was observed, together with pulmonary infiltrate. The patient was submitted to lung and liver biopsies, which revealed noncaseating granulomas. The clinical, radiological and histopathological findings were consistent with sarcoidosis and lymph node amyloidosis. The combination of sarcoidosis and amyloidosis has rarely been reported.

Keywords: Amyloidosis; Sarcoidosis; Lymph nodes.

Objective: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. Methods: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. Results: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = −0.90; p = 0.04). Conclusions: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

Keywords: Sarcoidosis; Granulomatous disease, chronic; Extracellular matrix; Immunophenotyping; Respiratory function tests.

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 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: Behcet's syndrome, or Behcet's disease (BD), is a multisystem pathology, and survival is related to pulmonary involvement. However, it appears that different treatments correlate with different prognoses. The aim of this study was to evaluate clinical and tomographic evolution, as well as the survival, of patients with BD-related pulmonary involvement. Methods: A retrospective review of our experience with pulmonary manifestations in patients with BD treated at our institution between January 1, 1988 and April 30, 2006. The clinical, radiological, treatment and survival data were obtained from medical charts. Results: We identified 9 patients with BD-related pulmonary involvement. The mean age was 34 ± 11.5 years, and 7 of the patients were male. The radiological findings were as follows: pulmonary artery aneurysm (PAA) in 8 patients; pulmonary embolism in 3 (translating to an incidence of 5.11 cases/100 patient-years); alveolar hemorrhage in one; and pulmonary hypertension in one. The treatment consisted of immunosuppression with prednisone plus chlorambucil (or cyclophosphamide or mycophenolate mofetil) in all patients, with partial or complete resolution of the PAAs. One patient with a PAA and pulmonary hypertension also received sildenafil and warfarin, with good clinical and tomographic response (the first report in the English literature). In our sample, the mean duration of the follow-up period was 6.52 years. The three-year survival rate was 88.8%, as was the five-year survival rate. Conclusions: Patients with BD-related pulmonary involvement can present good survival with immunosuppressive therapy, and BD should be borne in mind as a possible cause of pulmonary hypertension and alveolar hemorrhage.

Keywords: Behcet Syndrome; Lung diseases, interstitial; Pulmonary circulation; Hypertension, pulmonary; Pulmonary embolism; Alveolar.

In a 62-year-old white woman, submitted to preoperative evaluation for facectomy, urinary alterations were detected. The diagnosis established included left-sided kidney stones and homolateral exclusion. At pre-nephrectomy, interstitial widespread lung disease and thoracic adenopathy were evidenced and their investigation was postponed to after surgery. In the removed kidney, non cascous epithelioid granulomas were found. Later, transbronchial biopsy disclosed this same aspect. The patient was treated with methylprednisolone and presented slight pulmonary improvement, though no amelioration in renal function occurred. Final diagnosis was sarcoidosis with lung, thoraco-lymphatic and renal involvement.

Keywords: Sarcoidosis. Kidney failure. Pulmonary sarcoidosis.

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.

Objective: Evaluation of enlarged mediastinal lymph nodes is crucial for patient management. Malignant lymphoma and sarcoidosis are often difficult to differentiate. Our objective was to determine the diagnostic accuracy of MRI for differentiating between sarcoidosis and malignant lymphoma. Methods: This was a retrospective study involving 47 patients who underwent chest MRI and were diagnosed with one of the diseases between 2017 and 2019. T1, T2, and diffusion-weighted signal intensity were measured. Apparent diffusion coefficients (ADCs) and T2 ratios were calculated. The diagnostic performance of MRI was determined by ROC analysis. Results: Mean T2 ratio was significantly lower in the sarcoidosis group than in the lymphoma group (p = 0.009). The T2-ratio cutoff value that best differentiated between lymphoma-related and sarcoidosis-related enlarged lymph nodes was 7.1, with a sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of 58.3%, 95.6%, 76.5%, 93.3%, and 68.7%, respectively. The mean ADC was significantly lower in the lymphoma group than in the sarcoidosis group (p = 0.002). The ADC cutoff value that best differentiated between lymphoma-related and sarcoidosis-related enlarged lymph nodes was 1.205, with a sensitivity, specificity, positive predictive value, negative predictive value and accuracy of 87.5%, 82.6%, 85.1%, 84.0% and 86.3%, respectively. No significant differences were found between the two groups regarding T1 signal intensity, T2 signal intensity, and lymph node diameter. Conclusions: MRI parameters such as ADC, diffusion, and T2 ratio can be useful in the differentiation between sarcoidosis and lymphoma in the evaluation of enlarged lymph nodes.

Keywords: Diffusion magnetic resonance imaging; Lymphoma; Lymph nodes; Sarcoidosis.

The authors report a typical case of pediatric sarcoidosis presenting a granulomatous pulmonary disease with systemic impairment, reviewing clinical, diagnostic, and particular aspects of the disease in this age group, with emphasis on the difficulty to differentiate its diagnosis from that of tuberculosis.

Keywords: Sarcoidosis. Pulmonary sarcoidosis. Lung diseases.