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Cells Mar 2021Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and... (Review)
Review
Sarcoidosis is a multi-system disease of unknown etiology characterized by the formation of granulomas in various organs. It affects people of all ethnic backgrounds and occurs at any time of life but is more frequent in African Americans and Scandinavians and in adults between 30 and 50 years of age. Sarcoidosis can affect any organ with a frequency varying according to ethnicity, sex and age. Intrathoracic involvement occurs in 90% of patients with symmetrical bilateral hilar adenopathy and/or diffuse lung micronodules, mainly along the lymphatic structures which are the most affected system. Among extrapulmonary manifestations, skin lesions, uveitis, liver or splenic involvement, peripheral and abdominal lymphadenopathy and peripheral arthritis are the most frequent with a prevalence of 25-50%. Finally, cardiac and neurological manifestations which can be the initial manifestation of sarcoidosis, as can be bilateral parotitis, nasosinusal or laryngeal signs, hypercalcemia and renal dysfunction, affect less than 10% of patients. The diagnosis is not standardized but is based on three major criteria: a compatible clinical and/or radiological presentation, the histological evidence of non-necrotizing granulomatous inflammation in one or more tissues and the exclusion of alternative causes of granulomatous disease. Certain clinical features are considered to be highly specific of the disease (e.g., Löfgren's syndrome, lupus pernio, Heerfordt's syndrome) and do not require histological confirmation. New diagnostic guidelines were recently published. Specific clinical criteria have been developed for the diagnosis of cardiac, neurological and ocular sarcoidosis. This article focuses on the clinical presentation and the common differentials that need to be considered when appropriate.
Topics: Diagnosis, Differential; Humans; Organ Specificity; Phenotype; Sarcoidosis
PubMed: 33807303
DOI: 10.3390/cells10040766 -
Neurology(R) Neuroimmunology &... Nov 2021Although often regarded as a protean illness with myriad clinical and imaging manifestations, neurosarcoidosis typically presents as recognizable syndromes that can be... (Review)
Review
Although often regarded as a protean illness with myriad clinical and imaging manifestations, neurosarcoidosis typically presents as recognizable syndromes that can be approached in a rational, systematic fashion. Understanding of neurosarcoidosis has progressed significantly in recent years, including updated diagnostic criteria and advances in treatment. The diagnosis of neurosarcoidosis is established by the clinical syndrome, imaging and histopathological findings, and exclusion of other causes. Mounting evidence supports the use of tumor necrosis factor inhibitors as an important addition to the therapeutic armamentarium, along with glucocorticoids and steroid-sparing cytotoxic immunosuppressants. In this narrative review, we summarize recent advances in the diagnosis and treatment of neurosarcoidosis.
Topics: Central Nervous System Diseases; Humans; Sarcoidosis
PubMed: 34607912
DOI: 10.1212/NXI.0000000000001084 -
The European Respiratory Journal Dec 2021The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending...
BACKGROUND
The major reasons to treat sarcoidosis are to lower the morbidity and mortality risk or to improve quality of life (QoL). The indication for treatment varies depending on which manifestation is the cause of symptoms: lungs, heart, brain, skin or other manifestations. While glucocorticoids remain the first choice for initial treatment of symptomatic disease, prolonged use is associated with significant toxicity. Glucocorticoid-sparing alternatives are available. The presented treatment guidelines aim to provide guidance to physicians treating the very heterogenous sarcoidosis manifestations.
METHODS
A European Respiratory Society Task Force committee composed of clinicians, methodologists and patients with experience in sarcoidosis developed recommendations based on the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) methodology. The committee developed eight PICO (Patients, Intervention, Comparison, Outcomes) questions and these were used to make specific evidence-based recommendations.
RESULTS
The Task Force committee delivered 12 recommendations for seven PICOs. These included treatment of pulmonary, cutaneous, cardiac and neurologic disease as well as fatigue. One PICO question regarding small-fibre neuropathy had insufficient evidence to support a recommendation. In addition to the recommendations, the committee provided information on how they use alternative treatments, when there was insufficient evidence to support a recommendation.
CONCLUSIONS
There are many treatments available to treat sarcoidosis. Given the diverse nature of the disease, treatment decisions require an assessment of organ involvement, risk for significant morbidity, and impact on QoL of the disease and treatment.
Topics: Fatigue; Humans; Quality of Life; Sarcoidosis
PubMed: 34140301
DOI: 10.1183/13993003.04079-2020 -
Frontiers in Immunology 2020Sarcoidosis is a systemic disease of unknown etiology defined by the presence of noncaseating granulomatous inflammation that can cause organ damage and diminished... (Review)
Review
Sarcoidosis is a systemic disease of unknown etiology defined by the presence of noncaseating granulomatous inflammation that can cause organ damage and diminished quality of life. Treatment is indicated to protect organ function and decrease symptomatic burden. Current treatment options focus on interruption of granuloma formation and propagation. Clinical trials guiding evidence for treatment are lacking due to the rarity of disease, heterogeneous clinical course, and lack of prognostic biomarkers, all of which contribute to difficulty in clinical trial design and implementation. In this review, a multidisciplinary treatment approach is summarized, addressing immunuosuppressive drugs, managing complications of chronic granulomatous inflammation, and assessing treatment toxicity. Discovery of new therapies will depend on research into pathogenesis of antigen presentation and granulomatous inflammation. Future treatment approaches may also include personalized decisions based on pharmacogenomics and sarcoidosis phenotype, as well as patient-centered approaches to manage immunosuppression, symptom control, and treatment of comorbid conditions.
Topics: Clinical Trials as Topic; Humans; Immunosuppression Therapy; Immunosuppressive Agents; Inflammation; Quality of Life; Sarcoidosis
PubMed: 33329511
DOI: 10.3389/fimmu.2020.545413 -
American Family Physician May 2016Sarcoidosis is a systemic disease of unknown etiology characterized by the presence of noncaseating granulomas in any organ, most commonly the lungs and intrathoracic...
Sarcoidosis is a systemic disease of unknown etiology characterized by the presence of noncaseating granulomas in any organ, most commonly the lungs and intrathoracic lymph nodes. A diagnosis of sarcoidosis should be suspected in any young or middle-aged adult presenting with unexplained cough, shortness of breath, or constitutional symptoms, especially among blacks or Scandinavians. Diagnosis relies on three criteria: (1) a compatible clinical and radiologic presentation, (2) pathologic evidence of noncaseating granulomas, and (3) exclusion of other diseases with similar findings, such as infections or malignancy. An early and accurate diagnosis of sarcoidosis remains challenging, because initial presentations may vary, many patients are asymptomatic, and there is no single reliable diagnostic test. Prognosis is variable and depends on epidemiologic factors, mode of onset, initial clinical course, and specific organ involvement. The optimal treatment for sarcoidosis remains unclear, but corticosteroid therapy has been the mainstay of therapy for those with significantly symptomatic or progressive pulmonary disease or serious extrapulmonary disease. Refractory or complex cases may require immunosuppressive therapy. Despite aggressive treatment, some patients may develop life-threatening pulmonary, cardiac, or neurologic complications from severe, progressive disease. End-stage disease may ultimately require lung or heart transplantation for eligible patients.
Topics: Biopsy, Fine-Needle; Bronchoalveolar Lavage; Diagnosis, Differential; Family Practice; Humans; Prognosis; Radiography, Thoracic; Respiratory Function Tests; Sarcoidosis; Sarcoidosis, Pulmonary
PubMed: 27175719
DOI: No ID Found -
Wiener Klinische Wochenschrift Nov 2016Fever of unknown origin (FUO) was originally characterised in 1961 by Petersdorf and Beeson as a disease condition of temperature exceeding 38.3 °C on at least three... (Review)
Review
Fever of unknown origin (FUO) was originally characterised in 1961 by Petersdorf and Beeson as a disease condition of temperature exceeding 38.3 °C on at least three occasions over a period of at least three weeks, with no diagnosis made despite one week of inpatient investigation. However, since underlying diseases are often reported for classical FUO, these presentations may not be considered to be of "unknown origin". Rather, the aetiology of prolonged fever may resolve, or not resolve. The definition of fever with unresolved cause (true FUO) is difficult, as it is a moving target, given the constant advancement of imaging and biomarker analysis. Therefore, the prevalence of fever with unresolved cause (FUO) is unknown.In this review, we report such a case of prolonged fever, which initially has presented as classical FUO, and discuss current literature. Furthermore, we will give an outlook, how a prospective study on FUO will allow to solve outstanding issues like the utility of different diagnostic investigations, and the types and prevalence of various underlying diseases.
Topics: Diagnosis, Differential; Evidence-Based Medicine; Fever of Unknown Origin; Humans; Male; Middle Aged; Sarcoidosis; Symptom Assessment; Treatment Outcome
PubMed: 27670857
DOI: 10.1007/s00508-016-1083-9 -
Journal of Cardiac Failure Jan 2022The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in... (Review)
Review
The prevalence of sarcoidosis-related cardiomyopathy is increasing. Sarcoidosis impacts cardiac function through granulomatous infiltration of the heart, resulting in conduction disease, arrhythmia, and/or heart failure. The diagnosis of cardiac sarcoidosis (CS) can be challenging and requires clinician awareness as well as differentiation from overlapping diagnostic phenotypes, such as other forms of myocarditis and arrhythmogenic cardiomyopathy. Clinical manifestations, extracardiac involvement, histopathology, and advanced cardiac imaging can all lend support to a diagnosis of CS. The mainstay of therapy for CS is immunosuppression; however, no prospective clinical trials exist to guide management. Patients may progress to developing advanced heart failure or ventricular arrhythmia, for which ventricular assist device therapies or heart transplantation may be considered. The existing knowledge gaps in CS call for an interdisciplinary approach to both patient care and future investigation to improve mechanistic understanding and therapeutic strategies.
Topics: Cardiomyopathies; Heart Failure; Heart Transplantation; Humans; Myocarditis; Sarcoidosis
PubMed: 34260889
DOI: 10.1016/j.cardfail.2021.06.016 -
European Respiratory Review : An... Jun 2021Epigenetic modifications are emerging as important regulatory mechanisms of gene expression in lung disease, given that they are influenced by environmental exposures... (Review)
Review
Epigenetic modifications are emerging as important regulatory mechanisms of gene expression in lung disease, given that they are influenced by environmental exposures and genetic variants, and that they regulate immune and fibrotic processes. In this review, we introduce these concepts with a focus on the study of DNA methylation and histone modifications and discuss how they have been applied to lung disease, and how they can be applied to sarcoidosis. This information has implications for other exposure and immunologically mediated lung diseases, such as chronic beryllium disease, hypersensitivity pneumonitis, and asbestosis.
Topics: DNA Methylation; Environmental Exposure; Epigenesis, Genetic; Humans; Lung Diseases; Sarcoidosis
PubMed: 34168064
DOI: 10.1183/16000617.0076-2021 -
Current Opinion in Pulmonary Medicine Sep 2021Epidemiological and clinical observations as well as familial clustering support the existence of a genetic predisposition to sarcoidosis. In this article, we review the... (Review)
Review
PURPOSE OF REVIEW
Epidemiological and clinical observations as well as familial clustering support the existence of a genetic predisposition to sarcoidosis. In this article, we review the most recent findings in genetics of sarcoidosis and discuss how the identification of risk alleles may help advancing our understanding of disease etiology and development.
RECENT FINDINGS
Genetic studies of sarcoidosis phenotypes have identified novel and ancestry-specific associations. Gene-environment interaction studies highlighted the importance of integrating genetic information when assessing the relationship between sarcoidosis and environmental exposures. A case-control-family study revealed that the heritability of sarcoidosis is only 49%, suggesting the existence of additional important contributors to disease risk. The application of whole-exome sequencing has identified associations with disease activity and prognosis. Finally, gene expression studies of circulating immune cells have identified shared and unique pathways between sarcoidosis and other granulomatous diseases.
SUMMARY
Sarcoidosis genetic research has led to the identification of a number of associations with both sarcoidoses per se and disease phenotypes. Newer sequencing technologies are likely to increase the number of genetic variants associated with sarcoidosis. However, studying phenotypically and ethnically homogeneous patient subsets remains critically important regardless of the genetic approach used.
Topics: Genetic Predisposition to Disease; Humans; Phenotype; Sarcoidosis; Exome Sequencing
PubMed: 34175860
DOI: 10.1097/MCP.0000000000000798 -
Annals of Medicine Dec 2022Sarcoidosis is a heterogeneous disease, which can affect virtually every body organ, even though lungs and intra thoracic lymph nodes are almost universally affected.... (Review)
Review
Sarcoidosis is a heterogeneous disease, which can affect virtually every body organ, even though lungs and intra thoracic lymph nodes are almost universally affected. The presence of noncaseating granulomas is the histopathological hallmark of the disease, and clinical picture depends on the organs affected. Data about interaction between sarcoidosis and comorbidities, such as cardiovascular and pulmonary diseases, autoimmune disorders, malignancy and drug-related adverse events are limited. Several lung conditions can be associated with sarcoidosis, such as pulmonary hypertension and fibrosis, making it difficult sometimes the differentiation between complications and distinctive pathologies. Their coexistence may complicate the diagnosis of sarcoidosis and contribute to the highly variable and unpredictable natural history, particularly if several diseases are recognised. A thorough assessment of specific disorders that can be associated with sarcoidosis should always be carried out, and future studies will need to evaluate sarcoidosis not only as a single disorder, but also in the light of possible concomitant conditions.Key messagesComorbidities in sarcoidosis are common, especially cardiovascular and pulmonary diseases.In the diagnostic workup, a distinction must be made between sarcoidosis-related complaints and complaints caused by other separate disorders. It can be very difficult to distinguish between complications of sarcoidosis and other concomitant conditions.The coexistence of multiple conditions may complicate the diagnosis of sarcoidosis, affect its natural course and response to treatment.
Topics: Granuloma; Humans; Lung; Lung Diseases; Sarcoidosis
PubMed: 35441568
DOI: 10.1080/07853890.2022.2063375