Association between sarcoidosis and HLA polymorphisms in a Czech population from Central Europe: focus on a relationship with clinical outcome and treatment.

Background: Sarcoidosis is an immune-mediated systemic disease with unknown etiology affecting the lung predominantly. The clinical manifestation of sarcoidosis is rather diverse ranging from Löfgren's syndrome to fibrotic disease. Also, it differs among patients with distinct geographical and ethnic origins, consistent with environmental and genetic factors' role in its pathogenesis. Of those, the polymorphic genes of the HLA system have been previously implicated in sarcoidosis. Therefore, we have performed an association study in a well-defined cohort of Czech patients aiming to define how variation in HLA genes, may contribute to disease origin and development. Materials and methods: Total of the 301 Czech unrelated sarcoidosis patients were diagnosed according to international guidelines. In those, HLA typing was performed using next-generation sequencing. The allele frequencies at six HLA loci (HLA-A,-B,-C,-DRB1,-DQA1, and -DQB1) observed in the patients were compared with HLA allele distribution determined in 309 unrelated healthy Czech subjects; sub-analyses of relationships between HLA and distinct sarcoidosis clinical phenotypes were performed. Associations were assessed by two-tailed Fischer's exact test with correction for multiple comparisons. Results: We report two variants, HLA-DQB1*06:02, and HLA-DQB1*06:04, as risk factors for sarcoidosis, and three variants, HLA-DRB1*01:01, HLA-DQA1*03:01, and HLA-DQB1*03:02 as protective factors. HLA-B*08:01, HLA-C*07:01, HLA-DRB1*03:01, HLA-DQA1*05:01, and HLA-DQB1*02:01 variants associated with Löfgren's syndrome, a more benign phenotype. HLA- DRB1*03:01 and HLA-DQA1*05:01 alleles were connected with better prognosis-chest X-ray (CXR) stage 1, disease remission, and non-requirement of corticosteroid treatment. The alleles HLA-DRB1*11:01 and HLA-DQA1*05:05 are associated with more advanced disease represented by the CXR stages 2-4. HLA-DQB1*05:03 associated with sarcoidosis extrapulmonary manifestation. Conclusion: In our Czech cohort, we document some associations between sarcoidosis and HLA previously described in other populations. Further, we suggest novel susceptibility factors for sarcoidosis, such as HLA-DQB1*06:04, and characterize associations between HLA and sarcoidosis clinical phenotypes in Czech patients. Our study also extends the role of the 8.1 ancestral haplotype (HLA-A*01:01∼HLA-B*08:01∼HLA-C*07:01∼HLA-DRB1*03:01∼HLA-DQA1*05:01∼HLA-DQB1*02:01), already implicated in autoimmune diseases, as a possible predictor of better prognosis in sarcoidosis. The general translational application of our newly reported findings for personalized patient care should be validated by an independent study from another, international referral center.

Exogenous lipoid pneumonia caused by chronic improper use of baby body oil in adult patient.

INTRODUCTION: Exogenous lipoid pneumonia (ELP) is an uncommon condition resulting from aspirating or inhaling fatlike material. These substances elicit a foreign body reaction and proliferative fibrosis in the lung. CASE REPORT: We report a case of a 38-year-old woman with bilateral pulmonary infiltration. There were no clinical symptoms of this infiltration at diagnosis. The infiltration was found coincidentally during the pre-operation examination before surgery. A chest computed tomography scan revealed bilateral lung consolidation, particularly in the S6 area on the right side. The transthoracic lung biopsy led to suspicion of ELP. Precise anamnesis confirms the diagnosis of ELP caused by chronic improper use of baby body oil. Two years after discontinuing "baby body oil therapy", a chest CT scan revealed partial regression of pulmonary infiltration. CONCLUSION: The diagnosis of exogenous lipoid pneumonia is often difficult as symptoms, signs, and radiographic findings are all rather non-specific. We would like to emphasize the role of precise case history in better identification of ELP.

[Sarcoidosis--diagnostics, prognosis and therapy. A retrospective analysis]. / Diagnostika, prognostické faktory a lécba sarkoidózy - retrospektivní analýza.

Sarcoidosis is systematic granulomatous disease of unknown etiology which can affect any organ. Sarcoidosis belongs to diseases called interstitial lung diseases. Our study is a retrospective analysis of 169 patients (100 females and 69 males), whom we diagnosed sarcoidosis at our pulmonary department in years 2005-2010. Aim of the analysis was to find out prognostic factors and to describe the course of disease. Median age of sarcoidosis patients was 48 years (20-79). Females : males ratio was 1.5 : 1. Non smoker : smoker (or former smoker) ratio was 2.2 : 1. Familial occurrence was observed in 4 patients (2.4%). At diagnosis, stage 0 was present in 6 (3.5%) patients, stage I in 58 (34%) patients, stage II in 84 (49.5%) patients, stage III in 18 (11%) patients, and stage IV in 3 (2%) patients. Diagnosis was confirmed by histology in 111 patients. In 76 patients there was extrapulmonary sarcoidosis. The coincidence of sarcoidosis with autoimmune diseases was observed in 10 patients; 6 patients developed trombembolic disease. One patient suffered from sarcoidosis with cystic fibrosis. Spontaneous resolution was seen in 65 (38.5%) patients; 37 (64%) stage I patients, 26 (31%) stage II patients, and 2 (11%) stage III patients. One hundred one patients (60%) received corticosteroids. Adverse events of corticosteroid therapy were observed in 28 (26%) patients. In sarcoidosis patients with spontaneous resolution, no relapse of disease was observed. On the other hand, eleven (11%) patients treated with glucocorticosteroids relapsed. Median time to sarcoidosis relapse was 6 months (2-34). The age under 40 years, the X-ray stage I or II, the high CD4/CD8 ratio in bronchoalveolar fluid, pulmonary involvement, and therapy need for a period shorter than 2 years were assessed as a significant good prognostic factors. Observed lethality of our patient cohort was 1.2% (2 patients; both deaths related to sarcoidosis).

[Hidden cystic fibrosis in patient suffering from sarcoidosis]. / Skrytá cystická fibróza u nemocného se sarkoidózou.

We describe a case of an adult patient, whom sarcoidosis was diagnosed at first and cystic fibrosis was also discovered 2 years later on. Cystic fibrosis and sarcoidosis are uncommon diseases that only rarely occur together. On the other hand, the coincidence of sarcoidosis and cystic fibrosis is possible, and, moreover, one of the diseases can remain undiagnosed long time. Relationship between sarcoidosis and cystic fibrosis seems not to be probable, in accordance with recent medical reports, and the coincidence of both conditions appears as sporadic.

[Pulmonary Langerhans cell histiocytosis--evaluation of the disease activity and treatment response using PET-CT (SUV(max) Pulmo/SUV(max) Hepar index). Description of own experience and literature review]. / Plicní forma histiocytózy z Langerhansových bunk-- hodnocení aktivity nemoci a lécebné odpovedi pomocí PET-CT (indexu SUV(max) Pulmo/SUV(max) Hepar). Popis vlastních zkuseností a prehled literatury.

Pulmonary Langerhans cell histiocytosis (LCH) manifests with dyspnoea and a cough with no significant expectoration, with spontaneous pneumothorax being the first symptom in some patients. The disease is caused by multiple granulomas in terminal bronchioles, visible on high resolution CT (HRCT) as nodules. During the further course of the disease, these nodules progress through cavitating nodules into thick-walled and, subsequently, thin-walled cysts. LCH may affect the lungs only or multiple organs simultaneously. Pulmonary LCH may continually progress or remit spontaneously. Treatment is indicated in patients in whom pulmonary involvement is associated with multi-system involvement or when a progression of the pulmonary lesions has been confirmed. To document the disease progression, examination of the lungs using HRCT is routinely applied. Increasing number of nodules suggests disease progression. However, determining the number of nodules is extremely difficult. Measuring radioactivity of the individual small pulmonary loci (nodules) using PET is not possible due to the high number and small size of the nodules. Our centre has a register of 23 patients with LCH; the pulmonary form had been diagnosed in 7 patients. A total of 19 PET and PET-CT examinations were performed in 6 of these patients. PET-CT was performed using the technique of maximum fluorodeoxyglucose accumulation in a defined volume of the right lung--SUV(max) Pulmo. In order to compare the results of examinations performed using the same and different machines over time as well as in order to evaluate pulmonary activity, the maximum fluorodeoxyglucose accumulation in a defined volume of the right lung (SUV(max) Pulmo) to maximum fluorodeoxyglucose accumulation in a defined volume of the liver tissue (SUV(max) Hepar) ratio (index) was used. The disease progression was evaluated using the SUV(max) Pulmo/SUV(max) Hepar index in the six patients with pulmonary LCH. The index value was compared to other parameters characterising the disease activity (HRCT of the lungs, examination of pulmonary function and clinical picture). The SUV(max) Pulmo/SUV(max) Hepar index correlated closely with other disease activity parameters. The traditional PET-CT examination is useful in detecting the LCH loci in the bone, nodes and other tissue but not in the presence of diffuse involvement of pulmonary parenchyma. Measuring the maximum fluorodeoxyglucose accumulation in a defined volume of the right lung and expressing this activity as the SUV(max) Pulmo/SUV(max) Hepar index appears to be a promising approach. Our initial experience suggests that the results obtained using this method correlate well with other parameters that characterise activity of pulmonary LCH. However, this is a pilot study and further verification is required.

[Idiopathic pulmonary fibrosis]. / Idiopatická plicní fibróza.

Idiopathic pulmonary fibrosis (IPF), known in Europe as cryptogenic fibrosing alveolitis, is a rare, progressive and usually fatal form of idiopathic interstitial pneumonia. IPF is characterized by failure of alveolar re-epithelization, persistence of fibroblasts, deposition of extracellular matrix, and distortion of lung architecture which ultimately results in respiratory failure. Current consensus statements reserve the term IPF to refer to a specific clinical entity associated with the histopatological pattern of usual interstitial pneumonia (UIP). UIP is characterized by temporal heterogeneity, with alternating areas of interstitial fibrosis, fibroblastic foci (areas of proliferating fibroblasts and myofibroblasts), inflammation, honeycomb lung, and normal parenchyma. Fibroblastic foci are associated with progressive disease. Treatment of IPF remains clinical problem. Currently, there is no conservative therapy improving the survival of patients. Lung transplantation, however, improves survival. Identification of pathways crucial to fibrogenesis might offer potentially novel therapeutic targets to slow or halt progression of IPF.