Löfgren's Syndrome Research Articles

Genetic predisposition to sarcoidosis: another brick in the wall: Table 1–

The belief that a genetic susceptibility to the development of sarcoidosis exists is supported by several lines of evidence: 1) monozygotic twins are more often concordant for the disease than dizygotic twins; 2) sarcoidosis patients are more likely than healthy subjects to report a sibling or parent affected with the disease; 3) prevalence, incidence and severity of sarcoidosis vary widely amongst different races [1–4]. According to our current understanding of the disease pathophysiology, sarcoidosis is not due to defects in a single major gene or chemical pathway; instead, it is a complex disease that likely results from multiple genetic and environmental factors working together, each contributing a relatively small effect and few, if any, being absolutely required for the disease to occur. Genetics is also likely to contribute to the wide variety of clinical presentations and phenotypes observed in sarcoidosis. In this regard, some believe that sarcoidosis represents a family of diseases (sarcoidoses), including, among others: Lofgren syndrome, which is defined as the acute onset of fever, erythema nodosum, bilateral hilar lymphadenopathy and polyarthralgia; non-resolving/progressive lung disease; and granulomatous uveitis, each with potentially distinct genetic associations [5]. Berylliosis could also be considered as a subset of the broad grouping “sarcoidosis”. Traditionally, genetic studies have used a “candidate gene case–control” approach, particularly in the context of rare diseases, like sarcoidosis, because of the difficulties in recruiting large numbers of pedigrees (linkage study) or even larger numbers of well phenotyped subjects (genome-wide association study; GWAS). In candidate gene case–control studies, the distribution of common genetic variations (single nucleotide polymorphisms; SNPs) in the gene(s) of interest is compared between unrelated, affected individuals and matched healthy controls. This hypothesis-based methodology requires understanding of the disease pathophysiology, judicious selection of candidate genes based on their biological plausibility, and knowledge …

Sarkoidose: aktuelle Diagnostik und Therapie

Sarcoidosis is a multisystemic granulomatous disorder of unknown origin, which can involve multiple organs. However the lymph node and lung manifestations dominate. Most frequent symptoms are cough, fatigue, dyspnea and exercise limitations. About one third of the patients have no symptoms. The lung function test is mostly restrictive. The clinical course is very variable, spontaneous remissions occur in about 60 %. Acute sarcoidosis is a highly inflammatory disease with a very good prognosis even without steroid therapy. Chronic pulmonary sarcoidosis can lead to progressive loss of lung function. Indications to therapy are severe symptoms and loss of lung function as well as progressive lung involvement with fibrosis pattern. In chronic disease corticosteroids are effective in the majority of patients. Other immunosuppressives, cytotoxic and immunomodulatory agents are reserved for patients with severe side-effects to steroid-therapy or for patients, who cannot maintained on reasonable low doses of steroids. Lung transplantation is an option for life-threatening cases failing medical therapy.

Lofgren syndrome: Acute Variant of Sarcoidosis, A case report

Lofgren's syndrome is an acute form of sarcoidosis that is characterized by erythema nodosum (EN), bilateral hilar lymphadenopathy (BHL) accompanied by arthritis or arthralgia. We are reporting a 32 year old male with Lofgren's syndrome and then the literature is reviewed. Keywords: lofgren's syndrome, sarcoidosis.DOI: http://dx.doi.org/10.3329/kyamcj.v2i1.13520 KYAMC Journal Vol.2(1) 2011 pp.145-148

Lofgren's Syndrome-Acute Onset Sarcoidosis and Polyarthralgia: A Case Report

Lofgren's syndrome is an acute form of sarcoidosis characterized by erythema nodosum, bilateral hilar lymphadenopathy (BHL), and polyarthralgia or polyarthritis. This syndrome is common among Caucasians but rare in the Korean population. A 44-year-old woman was admitted to our hospital complaining of polyarthralgia. A chest radiograph revealed BHL and nodular shadows. Angiotensin-converting enzyme levels were within the normal range. Tissue biopsy from a mediastinum lymph node showed noncaseating granulomas. We diagnosed her with Lofgren's syndrome, an acute form of sarcoidosis.

Predictors of deterioration of symptoms and quality of life in patients with sarcoidosis

Introduction. The most frequent clinical outcomes in sarcoidosis patients are typically focused on the objective measurements of functions of the involved organs, but, generally, they do not take into account the individual perception of patients? everyday functioning. The aim of this study was to determine the type of association between the subjective disease outcomes and other objective conventional parameters in patients with sarcoidosis. Material and Methods. In the cross-sectional study including 172 sarcoidosis patients (122 females), quality of life was measured by a generic instrument, i.e. fifteen-dimensional measure of health-related quality of life together with a respiratory specific instrument, i.e. St George?s Respiratory Questionnaire; symptoms of fatigue were measured by Fatigue Scale and dyspnea was measured by the Basal Dyspnea Index. Body-mass index and the course of the disease (acute vs. chronic) were also evaluated. Pulmonary function was assessed by spirometry. Results. Acute sarcoidosis was present in 48 (28%) patients. Mean body mass index was 27.01?5.2. Only 20 (12%) patients had lower forced expiratory volume in one second values (<80%) that indicated the existance of obstructive ventilatory impairment. Multivariate linear regression analysis revealed that body mass index, clinical course of disease and spirometric parameter forced expiratory volume in one second were the significant predictors (R2=0.929, p<0.01) of sarcoidosis related fatigue (B=0.061, B=0.406, B=0.452; respectively). Body mass index and forced expiratory volume in one second were the only parameters that significantly predicted both patients? quality of life (R2=0.932; B=0.017, B=0.263) and dyspnea (R2=0.847; B=0.025, B=0.668). Conclusions. It is important to measure both subjective patient-reported outcomes and objective disease parameters in sarcoidosis since they represent different aspects of the disease. All applied measuring instruments for the examined subjective outcomes demonstrated good measuring properties.

Tumor necrosis factor-α production by blood mononuclear cells in different manifestations of sarcoidosis

Summary. Tumor necrosis factor-α (TNF-α) is a polypeptide mediator and proinflammatory cytokine that plays an important role for pathogenesis of sarcoidosis. The aim of this study was to investigate spontaneous and induced by M.bovis antigen (BCG) and mitogen concanavalin (Con A) production of TNF-α by peripheral blood mononuclear cells in patients with different manifestations of sarcoidosis. The study involved 22 patients with active sarcoidosis of intrathoracic lymph nodes and lungs. TNF-α production was studied in supernatants of blood mononuclear cell cultures using sandwich method and immunoenzyme analysis (ELISE). We found a significant increase in spontaneous and induced TNF-α production in patients with acute sarcoidosis compared to asymptomatic patients and with healthy volunteers. TNF-α hyperproduction induced by non-specific mitogen Con A was also revealed in all sarcoidosis patients regardless of activity of the disease in comparison with healthy controls. These data may indicate an increased functional activity of the immune cells and their tendency to hyperreactivity in response to antigen in patients with sarcoidosis.

Associations of HLA-DRB1 genotype with clinical expression of sarcoidosis portuguese patients

Introduction: Sarcoidosis is a granulomatous multisystem disorder of unclear etiology that commonly affects the lungs (90%), heart, skin and central nervous system. There is evidence for a strong genetic predisposition. Several studies conducted in different population have reported association between sarcoidosis and HLA (Human Leukocyte Antigen) class I and class II alleles. In Swedish patients Grunewald et al (Respiratory Research, 2010) reported that HLA-DRB1*15 is associated with a chronic course of sarcoidosis while the presence of HLA-DRB1*01 and HLA-DRB1*04 protect against disease. It has been also described that the HLA-DRB1*03 allele is associated with Lofgren's Syndrome (LS), a distinct form of sarcoidosis. This syndrome is characterized by an acute onset with bilateral hilar lymphadenopathy, erythema nodosum (EN), ankle arthritis and has in general a favorable prognosis.

Two cases of familial Mediterranean fever associated with sarcoidosis (Lofgren's syndrome) and rheumatoid arthritis

Two cases of familial Mediterranean fever associated with sarcoidosis (<scp>L</scp>ofgren's syndrome) and rheumatoid arthritis

Lofgren's syndrome

British Journal of Hospital MedicineVol. 73, No. 3 Case ReportLofgren's syndromeK Sanyal, BE BourkeK SanyalSearch for more papers by this author, BE BourkeSearch for more papers by this authorK Sanyal; BE BourkePublished Online:16 Aug 2013https://doi.org/10.12968/hmed.2012.73.3.172AboutSectionsView articleView Full TextPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareShare onFacebookTwitterLinked InEmail View article References Arnold WJ (1993) Sarcoidosis. In: Kelley WN, Harris ED Jr, Ruddy S, Sledge CB, eds. Textbook of Rheumatology. 4th ed. WB Saunders, Philadelphia: 1429–34 Google ScholarBadrinas F, Moresa J, Fite E, Plasencia A (1989) A seasonal clustering of sarcoidosis. Lancet ii: 455–6 Crossref, Google ScholarBerkman YM (1985) Radiologic aspects of intrathoracic sarcoidosis. Semin Roentgenol 20: 356–75 Crossref, Medline, Google ScholarGrunewald J, Eklund A (2007) Sex-specific manifestation of Lofgren's syndrome. Am J Respir Crit Care Med 175: 40–4 Crossref, Medline, Google ScholarHedfoss E, Lindstrom F (1983) HLA-B8/DR3 in sarcoidosis. Correlation to acute onset of disease with arthritis. Tissue Antigen 22(3): 200–3 Crossref, Medline, Google ScholarHunninghake GW, Costabel U, Ando M et al. (1999) ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders. Sarcoidosis Vasc Diffuse Lung Dis 16(2): 149–73 Medline, Google ScholarMañá J, Gómez-Vaquero C, Montero A et al. (2007) Lofgren's syndrome. Am J Respir Crit Care Med 175: 40–4 Crossref, Medline, Google ScholarPerruquet JL, Harrington TM, Davies DE, Viozi FJ (1984) Sarcoid arthritis in North American Caucasian population. J Rheumatol 11: 521–5 Medline, Google ScholarReich JM (2002) Mortality of intrathoracic sarcoidosis in referral vs. population based settings: Influence of stage, ethnicity and corticosteroid therapy. Chest 121: 32–9 Crossref, Medline, Google ScholarSpilberg J, Stilzbach LE, McEwen CE (1969) The arthritis of sarcoidosis. Arthritis Rheum 12: 126–37 Crossref, Medline, Google ScholarStiltzbach LE, James DG, Neville E et al. (1974) Course and prognosis of sarcoidosis around the world. Am J Med 57: 847–52 Crossref, Medline, Google Scholar FiguresReferencesRelatedDetails 1 March 2012Volume 73Issue 3ISSN (print): 1750-8460ISSN (online): 1759-7390 Metrics History Published online 16 August 2013 Published in print 1 March 2012 Information© MA Healthcare LimitedPDF download

Utility of KL-6/MUC1 in the clinical management of interstitial lung diseases

Interstitial lung diseases (ILDs) are a diverse group of pulmonary disorders characterized by various patterns of inflammation and fibrosis in the interstitium of the lung. Because injury and/or regeneration of type II pneumocytes are prominent histological features of ILDs, substances derived from type II pneumocytes have been the focus of research investigating potential biomarkers for ILD. One important biomarker for ILD is the high-molecular-weight glycoprotein, Krebs von den Lungen-6 (KL-6). KL-6 is now classified as a human MUC1 mucin protein, and regenerating type II pneumocytes are the primary cellular source of KL-6/MUC1 in the affected lungs of patients with ILD. KL-6/MUC1 is detectable in the serum of patients with ILD, and extensive investigations performed primarily in Japan have revealed that serum KL-6/MUC1 is elevated in 70-100% of patients with various ILDs, including idiopathic interstitial pneumonias, collagen vascular disease-associated interstitial pneumonia, hypersensitivity pneumonia, radiation pneumonitis, drug-induced ILDs, acute respiratory distress syndrome, pulmonary sarcoidosis, and pulmonary alveolar proteinosis. The results from these various studies have supported the utility of KL-6/MUC1 as a serum biomarker for detecting these various ILDs. Moreover, KL-6/MUC1 serum levels have been demonstrated to be useful for evaluating disease activity and predicting the clinical outcomes of various ILD types. Based on these observations, we believe that KL-6/MUC1 is currently one of the best and most reliable serum biomarkers available for ILD management.

HLA associations and Löfgren’s syndrome

Patients with sarcoidosis can be subgrouped according to organ engagement and clinical manifestations. One such subgroup is Löfgren’s syndrome (LS), constituting a distinct group of sarcoidosis patients with typical clinical manifestations, separate genetic associations and an immune response that seems to differ from that of non-LS patients. In particular, LS patients have strong associations with HLA-DRB1 alleles, and the well-known association with HLA-DRB1*03 is particularly striking. This particular HLA-DRB1 allele is also a very strong marker within that particular group of patients for a prognostically favorable disease course. This article will mainly discuss genetic associations with LS, and the possible implications of such associations.

A 44-Year-Old Man With Lofgren's Syndrome and the Highest Reported SUV of Mediastinal Lymphadenopathy on Whole-Body FDG PET Sca

INTRODUCTION: Whole-body fluorodeoxyglucose (FDG) positron emission tomography (PET) scans can be utilized in identifying occult granulomas in patients with Sarcoidosis(1). The usual standardized uptake value (SUV) range is between 2.0 and 16.0 units(2). We present a case of a 47 year-old man with bilateral mediastinal and hilar adenopathy with an SUV score range from 12 to 24. These findings have not been previously reported in the literature.

Sarkoidose

Sarcoidosis is a multisystem disorder of unknown aetiology. The pathogenetic principle is a granulomatous inflammatory reaction, probably caused by an overwhelming cell-mediated immune response to an antigen. The disorder is characterised by an inflammatory infiltration by non-caseating granulomas developing in the affected organs. In most cases the lung is involved (> 90%) and a “classical” bilateral hilar lymphadenopathy develops and/or an increase of mostly reticulo-nodular opacities can be observed in chest X-ray. Basically sarcoidosis can affect each and every organ system, and up to 30% of patients show extrapulmonary involvement. Essential diagnostic procedures include chest X-ray, chest CT, bronchoscopy, pulmonary function testing and complementary determination of laboratory parameters. The clinical course is highly variable; however, in general the prognosis of sarcoidosis is good, and in most cases spontaneous recovery can be expected. This specifically applies to highly acute courses such as bilateral hilar lymphadenopathy syndrome (Lofgren's syndrome). However, at least 10% of untreated cases develop chronic progressive courses with relevant impairment of organ systems eventually resulting in premature death (e.g. pulmonary fibrosis). If any therapy is required at all, long-term administration of glucocorticoids is the basic element of treatment in sarcoidosis. In rare cases the administration of more potent immunosuppressive drugs such as methotrexate, azathioprine, or cyclophosphamide is required.

Acute sarcoidosis as parotid fever in rheumatoid arthritis under anti-tumor necrosis factor- therapy

Acute sarcoidosis as parotid fever in rheumatoid arthritis under anti-tumor necrosis factor- therapy

Combined Intra- and Extracranial Cryptococcal Infection of a 20-Year-Old Patient in Right Temporal Area

Fungal disease in the head and neck area caused by saprophytic Cryptococcus neoformans is a rare condition in immunocompetent patients. However, patients with acquired immunodeficiency syndrome, leukemia, or Hodgkin’s lymphoma are at a high risk of developing serious life-threatening diseases with meningitis and pulmonary involvement. A 20-year-old man with a history of acute lymphatic leukemia and sarcoidosis presented with a 3-month history of a painful swelling in the right temporal region. Initially, removal of the third molar was performed, which did not alleviate the symptoms. After having consulted different medical services, the patient was referred to the craniomaxillofacial surgery department. A computed tomography scan revealed a right temporal soft tissue swelling with a hypodense central area and a defect in the temporal bone. After 2 incisions on the basis of a diagnosis of a temporal abscess had been performed without any improvement, a biopsy and additional microbiologic examination were initiated. The histologic and microbiologic workup confirmed the diagnosis of cryptococcosis. Fluconazole was administered for several months and all signs and symptoms of the infection resolved. The workup of the present case emphasizes the importance of the preservation of sufficient material for microbiologic examination in atypical cases of infections in the head and neck area.

Response to: Dr. Reich, Pro rebuttal: The treatment of the granulomatous response is beneficial in acute sarcoidosis

Response to: Dr. Reich, Pro rebuttal: The treatment of the granulomatous response is beneficial in acute sarcoidosis

Response to: Dr. Culver, Con rebuttal: The treatment of the granulomatous response is beneficial in acute sarcoidosis

Response to: Dr. Culver, Con rebuttal: The treatment of the granulomatous response is beneficial in acute sarcoidosis

Pro: The treatment of the granulomatous response is beneficial in acute sarcoidosis

Corticosteroids effectively suppress granulomatous inflammation in sarcoidosis. However, the role of corticosteroids remains unsettled nearly sixty years after the first report of their benefits. As in other contentious areas of medicine, we prioritize evidence from controlled clinical trials to guide decision-making. Despite the paucity of randomized, double-blind controlled evidence, the preponderance of data from the available trials is congruent: treatment of acute sarcoidosis is “on-balance” beneficial. To provide focus, I will limit my comments to recent-onset pulmonary sarcoidosis, defined as less than five years since diagnosis.

Con: The treatment of the granulomatous response is beneficial in acute sarcoidosis

Absent compelling indications such ashypercalcemia or cardiac involvement, the decision to inter-vene withcorticosteroidtherapy (CST)typically ariseswithinthefirsttwoyearsoutofconcernthatthisoutcomemayensuein persons with unresolving pulmonary shadowing.Izumi, in a seminal case-control study of largelyasymptomatic, predominantly stage I sarcoidosis, observeda marked adverse effect of elective CST.

Granulomatous tattoo reaction induced by intense pulse light treatment

Cosmetic tattooing involves implantation of pigments into the dermis in order to create a permanent makeup. Here, we report a case of sarcoidal granulomatous reaction to old cosmetic tattoos after an intense pulsed light (IPL) treatment for facial skin rejuvenation. We consider this case as a peculiar example of photo-induced reaction to tattoo. In addition, we hypothesize that an underlying immune dysfunction was present, and acted as a predisposing factor for this unusual response, as the patient had suffered from an episode of acute pulmonary sarcoidosis 15 years before. Overall, our observation suggests that IPL treatment should be used cautiously in patients with tattoos, especially when a history of autoimmune disease is present.