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Electronic nose (eNose) technology is an emerging diagnostic application, using artificial intelligence to classify human breath patterns. These patterns can be used to diagnose medical conditions. Sarcoidosis is an often difficult to diagnose disease, as no standard procedure or conclusive test exists. An accurate diagnostic model based on eNose data could therefore be helpful in clinical decision-making. The aim of this paper is to evaluate the performance of various dimensionality reduction methods and classifiers in order to design an accurate diagnostic model for sarcoidosis. Various methods of dimensionality reduction and multiple hyperparameter optimised classifiers were tested and cross-validated on a dataset of patients with pulmonary sarcoidosis ( n = 224) and other interstitial lung disease ( n = 317). Best performing methods were selected to create a model to diagnose patients with sarcoidosis. Nested cross-validation was applied to calculate the overall diagnostic performance. A classification model with feature selection and random forest (RF) classifier showed the highest accuracy. The overall diagnostic performance resulted in an accuracy of 87.1% and area-under-the-curve of 91.2%. After comparing different dimensionality reduction methods and classifiers, a highly accurate model to diagnose a patient with sarcoidosis using eNose data was created. The RF classifier and feature selection showed the best performance. The presented systematic approach could also be applied to other eNose datasets to compare methods and select the optimal diagnostic model., (© 2023 IOP Publishing Ltd.)

Objective: To investigate the diagnostic and staging value of serum angiotensin-converting enzyme (sACE) in sarcoidosis., Methods: Patients with suspected sarcoidosis treated in the Department of Pulmonary and Critical Care Medicine of the China-Japan Friendship Hospital from 2010 to 2020 were included. The data of sACE, erythrocyte sedimentation rate (ESR), complete blood count (CBC), lung function, bronchoalveolar lavage, and biopsy were collected. The differences between the sarcoidosis group and the nonsarcoidosis group and between different stages of sarcoidosis were compared. The receiver operating characteristic (ROC) curve analysis was used for the diagnostic test of sACE in sarcoidosis., Results: A total of 84 cases with suspected sarcoidosis were included, among which 70 cases were confirmed to be sarcoidosis by biopsy. The mean value of sACE in sarcoidosis patients was 56.61 ± 30.80 U/L, which was significantly higher than that in nonsarcoidosis patients (28.07 ± 14.11 U/L, P = 0.001). The level of sACE in sarcoidosis patients with peripheral superficial lymph nodes and multiple system involvement was significantly higher than that in intrathoracic sarcoidosis patients ( P = 0.009); the percentage of lymphocytes in bronchoalveolar lavage fluid (BALF) of sarcoidosis patients was 45.39 ± 22.87%, which was significantly higher than that of nonsarcoidosis patients ( P < 0.001). There was no correlation between sACE and ESR (correlation coefficient = -0.167). According to ROC curve analysis, when sACE ≥ 44.0 U/L, the sensitivity of sarcoidosis diagnosis was 61.4%, the specificity was 92.9%, and the AUC was 0.819., Conclusion: sACE has a good specificity in the diagnosis of sarcoidosis. sACE values in patients with sarcoidosis with systemic involvement were higher than those with simple intrathoracic sarcoidosis., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Wenqiao Wang et al.)

Sarcoidosis is a chameleon disease of unknown etiology, characterized by the growth of non-necrotizing and non-caseating granulomas and manifesting with clinical pictures that vary on the basis of the organs that are mainly affected. Lungs and intrathoracic lymph nodes are the sites that are most often involved, but virtually no organ is spared from this disease. Histopathology is distinctive but not pathognomonic, since the findings can be found also in other granulomatous disorders. The knowledge of these findings is important because it could be helpful to differentiate sarcoidosis from the other granulomatous-related diseases. This review aims at illustrating the main clinical and histopathological findings that could help clinicians in their routine clinical practice.

Abstract: Cutaneous sarcoidosis occurs in about one-quarter of patients with systemic disease and presents with either specific or nonspecific signs. Psoriasiform sarcoidosis is an uncommon presentation. Herein, study authors report a rare case of systemic sarcoidosis that presented with psoriasiform plaques and patchy alopecia. The main patient complaint was disfigurement from skin lesions over different areas of his body, followed by scalp alopecia and uveitis. These lesions were well-defined plaques, some oozing and others scaly. Dermoscopic examination revealed yellow-orange globular structure. A biopsy was taken; the eventual diagnosis was sarcoidosis, for which the patient received treatment with systemic steroids, resulting in improvement of all of his lesions. Physicians should suspect sarcoidosis in any patient presenting with psoriasiform skin lesions not responding to traditional psoriasis treatment., (Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.)

To analyze the frequency and clinical phenotype of neurosarcoidosis (NS) in one of the largest nationwide cohorts of patients with sarcoidosis reported from southern Europe. NS was evaluated according to the Diagnostic Criteria for Central Nervous System and Peripheral Nervous System Sarcoidosis recently proposed by Stern et al. Pathologic confirmation of granulomatous disease was used to subclassify NS into definite (confirmation in neurological tissue), probable (confirmation in extraneurological tissue) and possible (no histopathological confirmation of the disease). Of the 1532 patients included in the cohort, 85 (5.5%) fulfilled the Stern criteria for NS (49 women, mean age at diagnosis of NS of 47.6 years, 91% White). These patients developed 103 neurological conditions involving the brain (38%), cranial nerves (36%), the meninges (3%), the spinal cord (10%) and the peripheral nerves (14%); no patient had concomitant central and peripheral nerve involvements. In 59 (69%) patients, neurological involvement preceded or was present at the time of diagnosis of the disease. According to the classification proposed by Stern et al., 11 (13%) were classified as a definite NS, 61 (72%) as a probable NS and the remaining 13 (15%) as a possible NS. In comparison with the systemic phenotype of patients without NS, patients with CNS involvement presented a lower frequency of thoracic involvement (82% vs 93%, q = 0.018), a higher frequency of ocular (27% vs 10%, q < 0.001) and salivary gland (15% vs 4%, q = 0.002) WASOG involvements. In contrast, patients with PNS involvement showed a higher frequency of liver involvement (36% vs 12%, p = 0.02) in comparison with patients without NS. Neurosarcoidosis was identified in 5.5% of patients. CNS involvement prevails significantly over PNS involvement, and both conditions do not overlap in any patient. The systemic phenotype associated to each involvement was clearly differentiated, and can be helpful not only in the early identification of neurological involvement, but also in the systemic evaluation of patients diagnosed with neurosarcoidosis.

Background: Sarcoidosis is a systemic granulomatous disease of unknown etiology. Clinical cohort studies of different populations are important to understand the high variability in clinical presentation and disease course of sarcoidosis. The aim of the study is to evaluate clinical characteristics, including organ involvement, pulmonary function tests, and laboratory parameters, in a sarcoidosis cohort at the University of Minnesota. We compare the organ system involvement of this cohort with other available cohorts., Methods: We conducted a retrospective data collection and analysis of 187 subjects with biopsy-proven sarcoidosis seen at a tertiary center. Organ system involvement was determined using the WASOG sarcoidosis organ assessment instrument. Clinical phenotype groups were classified using the Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis criteria., Results: Mean subject age at diagnosis was 45.8 ± 12.4, with a higher proportion of males (55.1%), and a higher proportion of blacks (17.1%) compared to the racial distribution of Minnesota residents (5.95%). The majority (71.1%) of subjects required anti-inflammatory therapy for at least 1 month. Compared to the A Case Control Etiologic Study of Sarcoidosis cohort, there was a higher frequency of extra-thoracic lymph node (34.2% vs. 15.2%), eye (20.9% vs. 11.8%), liver (17.6% vs. 11.5%), spleen (20.9% vs. 6.7%), musculoskeletal (9.6% vs. 0.5%), and cardiac (10.7% vs. 2.3%) involvement in our cohort. A multisystem disease with at least five different organs involved was identified in 13.4% of subjects. A restrictive physiological pattern was observed in 21.6% of subjects, followed by an obstructive pattern in 17.3% and mixed obstructive and restrictive pattern in 2.2%. Almost half (49.2%) were Scadding stages II/III. Commonly employed disease activity markers, including soluble interleukin-2 receptor and angiotensin-converting enzyme, did not differ between treated and untreated groups., Conclusions: This cohort features a relatively high frequency of high-risk sarcoidosis phenotypes including cardiac and multiorgan disease. Commonly-utilized serum biomarkers do not identify subpopulations that require or do better with treatment. Findings from this study further highlight the high-variability nature of sarcoidosis and the need for a more reliable biomarker to predict and measure disease severity and outcomes for better clinical management of sarcoidosis patients.

Objectives : In sarcoidosis, the definition of organ involvement with traditional means appears laborious and somewhat controversial, and phenotyping by the above overlapping. 18 F-FDG PET/CT defines disease extent by activity more precisely, and may result in a better understanding of sarcoidosis disease behavior and phenotypes expression. We hypothesized that 18 F-FDG PET/CT could add in the phenotyping of sarcoidosis patients by unveiling in detail sites of involvement even in clinically and physiologically silent disease. Methods : This study was designed to investigate the role of 18 F-FDG PET/CT in phenotyping sarcoidosis using cluster analysis by adding this new means in the routine work-up of 195 s arcoidosis patients of a single academic center. Results : 18 F-FDG PET/CT succeeded to identify despite the random distribution of the disease, an ordered stratification into 4 phenotypes: I) thoracic nodal hilar-mediastinal, II) thoracic nodal hilar-mediastinal and lungs, III) an extended thoracic and extra-thoracic only nodal phenotype including inguinal-abdominal-supraclavicular stations, and IV) all the above plus systemic organs and tissues such as muscles-bones-spleen and skin. Conclusion : Though further studies are necessary to confirm findings as patterns of disease behavior; the proposed phenotypes may prove useful in the design of future studies with homogeneous cohorts facilitating in sarcoidosis patients a personalized medicine approach.

Aims: The aim of this study was to determine whether deep convolutional neural network (DCNN)-based features can represent the difference between cardiac sarcoidosis (CS) and non-CS using polar maps., Methods: A total of 85 patients (33 CS patients and 52 non-CS patients) were analyzed as our study subjects. One radiologist reviewed PET/CT images and defined the left ventricle region for the construction of polar maps. We extracted high-level features from the polar maps through the Inception-v3 network and evaluated their effectiveness by applying them to a CS classification task. Then we introduced the ReliefF algorithm in our method. The standardized uptake value (SUV)-based classification method and the coefficient of variance (CoV)-based classification method were used as comparative methods., Results: Sensitivity, specificity and the harmonic mean of sensitivity and specificity of our method with the ReliefF algorithm were 0.839, 0.870 and 0.854, respectively. Those of the SUVmax-based classification method were 0.468, 0.710 and 0.564, respectively, and those of the CoV-based classification method were 0.655, 0.750 and 0.699, respectively., Conclusion: The DCNN-based high-level features may be more effective than low-level features used in conventional quantitative analysis methods for CS classification., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

This original research is a directional study that determined the habits of individuals using four analyses to find statistical significance in the data collected from the surveys of 801 qualified of 1,340 individuals who agreed to participate. Results from the self-reported diagnosis of individuals affected by sarcoidosis produced seven statistically significant indicators of future research needed. The demographics revealed a significantly greater number of women and African-Americans participants than other minorities in the United States and suggested a sense of urgency to find a cure. Most important are the seven statistically significant findings that also gave credence to the researchers' four subdiagnostic classifications. They are acute sarcoidosis (AS) and chronic sarcoidosis with limited dissemination (CSLD), while more severe cases include those with chronic sarcoidosis with full dissemination including cutaneous involvement (CSFDIC) and chronic sarcoidosis with neurosarcoidosis (CSN). The most severe sarcoidosis cases (CSN) were on the "most likely" side of every statistically significant category except drinking alcohol, and the "least likely" to participate in physical activities. Conversely, the least severe case of sarcoidosis (AS) was the opposite. The complete list of statistically significant areas was related to alcohol use, tobacco use, ciprofloxacin use, environmental exposure to metals (copper, iron), infectious diseases (candidiasis), genetics, and physical exercise. Statistically, the most crucial study needed; emerged from the Rh blood grouping of the participants., (Copyright: © 2020.)

Background: Flexible bronchoscopy with endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA) is increasingly being used to obtain pathology specimens for diagnosis of sarcoidosis. There is wide variation in reported diagnostic yield in literature. New TBNA needles are available in the market but data are lacking about their diagnostic yield especially for sarcoidosis. This study reports the diagnostic yield of bronchoscopy with EBUS-TBNA using ViziShot FLEX 19-G needle in a series of patients with suspected sarcoidosis., Methods: This is a retrospective chart review for diagnostic yield of the 19-G EBUS-TBNA needle for suspected sarcoidosis., Results: Eighty-six EBUS bronchoscopies were performed, 15 were done with clinical suspicion of sarcoidosis. The 19-G needle was used for all cases of suspected sarcoidosis. The procedure was diagnostic of sarcoidosis in 14 (93.3%) patients by TBNA with 1 nondiagnostic bronchoscopy. Procedural diagnostic yield was 93.3%. Eighty-five percent (28/33) of sampled lymph nodes were positive for noncaseating granulomas. The yield of transbronchial lung biopsy (TBLB) and endobronchial lung biopsy was 38% (5/13) and 43% (6/14), respectively. TBLB and endobronchial lung biopsy did not add to the diagnostic yield of the procedure. No significant adverse events were noted., Conclusion: This series reports a higher diagnostic yield than most other published studies and opens platform for direct comparison of each available needle. It also adds to the safety data for this larger needle. In addition, it raises doubt into utility of TBLB for diagnosis of sarcoidosis, which can increase the procedural complications.

Previous studies attempted to characterize the subjects with sarcoidosis according to differences in sex, age, and the presence of specific organ involvement. However, significant interactions among these factors precluded a clear conclusion based on simple comparison. This study aimed to clarify the age- and sex-stratified prevalence of specific organ involvement and the heterogenous nature of sarcoidosis. Using the data of 9,965 patients who were newly registered into a database at the Ministry of Health, Labour and Welfare, Japan between 2002 and 2011, we evaluated the age- and sex-specific prevalence of the eye, lung, and skin involvement of sarcoidosis. We also attempted corresponding analysis considering multiple factors. As compared with several decades ago, the monophasic age distribution in men became biphasic, and the biphasic distribution in women, monophasic. The prevalence of pulmonary and cutaneous lesions was significantly associated with age, whereas the prevalence of ocular involvement showed a biphasic pattern. The prevalence of bilateral hilar lymphadenopathy was significantly higher, whereas the prevalence of diffuse lung shadow was significantly lower, in subjects with ocular involvement than those without ocular involvement. Corresponding analysis visually clarified the complex interactions among factors. Our results contribute to a better understanding of the heterogeneous features of sarcoidosis.

Background: The role of CD4 + T cells in the immunopathogenesis of pulmonary sarcoidosis is well-established, while less is known about the phenotype and function of CD8 + cytolytic T cells (CTLs)., Methods: CD8 + CTLs were explored in peripheral blood and bronchoalveolar lavage (BAL) samples obtained from up to 25 patients with sarcoidosis and 25 healthy controls. The proportion of CTLs was assessed by the expression of cytolytic effector molecules perforin, granzyme B and granulysin in CD8 + T cells, using flow cytometry. Cytolytic function in blood lymphocytes was assessed using a standard 51 Cr-release assay. Patients with Löfgren´s syndrome (LS) and an acute disease onset, were compared to non-LS patients with an insidious onset., Results: Higher proportions of peripheral CD8 + CTLs expressing perforin and granzyme B were observed in sarcoidosis compared to healthy controls. Blood CTLs from non-LS patients had significantly higher expression of perforin, granzyme B and granulysin compared to matched BAL, while LS patients maintained lower levels of effector molecules in both compartments. Mitogen-stimulated peripheral lymphocytes from sarcoidosis patients, particularly from the non-LS group, showed a higher target cell lysis compared to controls., Conclusion: These results demonstrated enhanced peripheral CD8 + CTL responses in sarcoidosis, especially in non-LS patients who have an increased risk of chronic disease. Further comprehensive clinical studies are warranted to increase our understanding of CD8 + CTL responses in sarcoidosis., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Aim: The aim of this study was to identify the frequency and prevalence of comorbidities in sarcoid patients and to assess their influence on overall mortality in the cohort of patients with sarcoidosis., Materials and Methods: A cohort of 557 patients with histologically confirmed sarcoidosis diagnosed between 2007 and 2011 and a group of non-sarcoid controls were observed. All patients were carefully observed for comorbidities and mortality., Results: 291 males (52.2%) and 266 females (47.8%) with mean age 48.4 ± 12.0 years in sarcoidosis group and a group of 100 controls with mean age (49.25 ± 10.3) were observed. The mean number of comorbidities in both groups was similar (0.9 ± 0.99 vs 0.81 ± 0.84 NS). The frequency of thyroid disease was significantly higher in sarcoidosis group comparing to controls at the time of diagnosis (OR = 3.62 P = 0.0144). During the observation period (median 58.0 months), 16 patients died (2.9%). The mean number of comorbidities was significantly higher in the groups of non-survivors as compared to survivors (2.8 ± 1.0, vs 0.8 ± 0.9), P < 0.0001., Conclusion: The comorbidity burden has strong impact on mortality in sarcoidosis. Thyroid diseases are more frequent in sarcoidosis than in non-sarcoid controls., (© 2015 John Wiley & Sons Ltd.)

Sarcoidosis is a granulomatous lung disorder of unknown cause. The majority of individuals with sarcoidosis spontaneously achieve full remission (uncomplicated sarcoidosis), however, ~20% of sarcoidosis-affected individuals experience progressive lung disease or cardiac and nervous system involvement (complicated sarcoidosis). We investigated peripheral blood mononuclear cell (PBMC) microRNA and protein-coding gene expression data from healthy controls and patients with uncomplicated or complicated sarcoidosis. We identified 46 microRNAs and 1,559 genes that were differentially expressed across a continuum of sarcoidosis severity (healthy control → uncomplicated sarcoidosis → complicated sarcoidosis). A total of 19 microRNA-mRNA regulatory pairs were identified within these deregulated microRNAs and mRNAs, which consisted of 17 unique protein-coding genes yielding a 17-gene signature. Pathway analysis of the 17-gene signature revealed Jak-STAT signaling pathway as the most significantly represented pathway. A severity score was assigned to each patient based on the expression of the 17-gene signature and a significant increasing trend in the severity score was observed from healthy control, to uncomplicated sarcoidosis, and finally to complicated sarcoidosis. In addition, this microRNA-regulated gene signature differentiates sarcoidosis patients from healthy controls in independent validation cohorts. Our study suggests that PBMC gene expression is useful in diagnosis of sarcoidosis.

Background: Sarcoidosis is a granulomatous inflammatory disease of unknown cause. Its prevalence in Germany is approximately 46 per 100 000 persons., Methods: This article is based on pertinent publications retrieved by a selective search in PubMed., Results: A presumptive diagnosis of sarcoidosis is made in any patient with a granulomatous inflammation that is not explained by any other identifiable cause, such as an infection or foreign body. Non-caseating granulomas containing epithelioid cells are its histological hallmark. Recently developed diagnostic techniques, including positron emission tomography and magnetic resonance imaging, have made it easier to detect organ involvement and to assess the activity of the disease. The pattern of organ involvement varies from patient to patient. Many patients have a systemic inflammatory reaction with subfebrile or febrile temperatures, night sweats, weight loss, diminished physical reserve, and fatigue. Sarcoidosis often resolves spontaneously. Detection of organ involvement is not necessarily an indication for treatment, but treatment is clearly needed if there is symptomatic cardiac involvement or any involvement of the central nervous system. Oral corticosteroids are the first line of treatment. Their long-term use can cause serious complications., Conclusion: The treatment of patients with sarcoidosis, particularly those with complicated disease courses, requires close collaboration of the primary care physician with a specialized interdisciplinary center.

The 1930 International Labour Office Conference on silicosis in Johannesburg identified silicosis by setting a medicolegal framework to its nosology: as with other occupational illnesses, its medical content was fixed under economic pressure. This article follows a reading of all the proceedings of this conference (debates and reports of experts) to examine their potential impact on the etiology and nosology of other diseases, specifically sarcoidosis and pulmonary alveolar proteinosis (PAP), "idiopathic" diseases in which inorganic particles may be involved. We propose renewed study of the role of inorganic particles in these diseases. To do this, we propose to mobilize detection means such as mineralogical analysis and electron microscopy and in depth interviewing that are currently seldom used in France, in order to establish diagnosis and the potential occupational and environmental origin of these diseases., (© 2015 Wiley Periodicals, Inc.)

Sarcoidosis is a systemic disease characterized by noncaseating granulomatous inflammation with tremendous clinical heterogeneity and uncertain pathobiology and lacking in clinically useful biomarkers. The Genomic Research in Alpha-1 Antitrypsin Deficiency and Sarcoidosis (GRADS) study is an observational cohort study designed to explore the role of the lung microbiome and genome in these two diseases. This article describes the design and rationale for the GRADS study sarcoidosis protocol. The study addresses the hypothesis that distinct patterns in the lung microbiome are characteristic of sarcoidosis phenotypes and are reflected in changes in systemic inflammatory responses as measured by peripheral blood changes in gene transcription. The goal is to enroll 400 participants, with a minimum of 35 in each of 9 clinical phenotype subgroups prioritized by their clinical relevance to understanding of the pathobiology and clinical heterogeneity of sarcoidosis. Participants with a confirmed diagnosis of sarcoidosis undergo a baseline visit with self-administered questionnaires, chest computed tomography, pulmonary function tests, and blood and urine testing. A research or clinical bronchoscopy with a research bronchoalveolar lavage will be performed to obtain samples for genomic and microbiome analyses. Comparisons will be made by blood genomic analysis and with clinical phenotypic variables. A 6-month follow-up visit is planned to assess each participant's clinical course. By the use of an integrative approach to the analysis of the microbiome and genome in selected clinical phenotypes, the GRADS study is powerfully positioned to inform and direct studies on the pathobiology of sarcoidosis, identify diagnostic or prognostic biomarkers, and provide novel molecular phenotypes that could lead to improved personalized approaches to therapy for sarcoidosis.

Purpose: To describe the ocular and systemic features in biopsy proven (definite) and non-biopsy proven (clinical) ocular sarcoidosis and to compare the ocular features with those proposed by the International Workshop for Ocular Sarcoidosis (IWOS)., Methods: Retrospective chart review of 83 patients who attended a tertiary referral uveitis clinic and were diagnosed with sarcoidosis. Patients were divided into two groups based on the type of diagnosis: those who had tissue biopsy confirmed diagnosis 'definite sarcoidosis' (n= 42; 50.60 %) and those who had 'clinical sarcoidosis' (n= 41; 49.40%). Ocular and systemic manifestations, including lung function tests and bronchoalveolar lavage findings were compared in the two groups. The ocular features were also compared with the categories laid down by the International Workshop on Ocular Sarcoidosis (IWOS)., Results: The mean age at presentation was 38.75 years (SD=12.33), 55.42% patients were female and mean follow-up was 24.35 months (SD=18.35). Trabecular meshwork nodules and/or tent-shaped PAS (category II of IWOS) were observed more frequently in patients with biopsy proven sarcoidosis (26.19 % v/s 9.76%; p=0.08). After logistic regression analysis, the predictor coefficient curve showed area under curve of 0.7262. Lymphocytosis (38.61% and 28.02%, p=0.93) and monocytosis (55.11% and 53.83%, p=0.56) on bronchoalveolar lavage analysis was present in both the groups, highlighting presence of granulomatous disease., Conclusion: This study suggests high reliability for the clinical diagnosis of ocular sarcoidosis in patients with signs recommended by IWOS and that our diagnostic criteria are consistent with that of the IWOS.

Background: Sarcoidosis is a systemic granulomatous multiorgan disease with the most common manifestation is in the chest, although the granulomas can also involve all other organs causing variety of symptoms mimicking different diseases., Objectives: To evaluate the incidence of comorbidity in a large group of patients with sarcoidosis diagnosed or followed in referral center for lung diseases in Poland., Patients and Methods: We performed a retrospective analysis in a group of 1779 patients discharged with the final diagnosis "sarcoidosis" (ICD-10: D86) from January 2008 to October 2011., Results: The majority (79.2%) were diagnosed as pulmonary and/or lymph node sarcoidosis (D86.0, D86.1, D86.2). Sarcoidosis of other and combined sites (D86.8) were diagnosed in 15.8% and unspecified (D86.9) in 5.0% of patients. At least one comorbid condition was noted in 54% of the patients, most frequently arterial hypertension (22.4%), thyroid disorders (5.6%), diabetes mellitus (5.0%), COPD (4.3%) and obesity (3.3%). Using linear regression models, the associations between the number of comorbidities and age and extent of the disease were found (p<0.001). Patients with multiorgan sarcoidosis were more likely to have a comorbid condition., Conclusions: More than half of patients with sarcoidosis have a comorbid condition, which is more likely in older patients and those with multiorgan involvement.

Background: The signs and symptoms of sinonasal sarcoidosis are diverse and nonspecific. It easily mimics more common sinonasal disorders such as allergic rhinitis, bacterial sinusitis, and atrophic rhinitis. The purpose of this study was to develop a classification system of sinonasal sarcoidosis that will help serve as a guide for both diagnosis and treatment., Methods: A retrospective chart review was performed of all patients diagnosed with sinonasal sarcoidosis from 1974 to 2013. A PubMed literature review of all published case series of sinonasal sarcoidosis was also reviewed., Results: The charts of 14 patients with biopsy-proven sinonasal sarcoidosis were reviewed. Follow-up time ranged from 6 months to 28 years. Presenting signs included hypertrophic mucosa, nasal polyps, crusting, nasal enlargement, and destructive processes. Eight patients underwent medical management alone and six patients underwent endoscopic sinus surgery. Five of the six patients were successfully treated with surgery. On review of the literature, 256 cases of sinonasal sarcoidosis were found, of which 43 patients underwent surgery. Clinical outcomes of the patients who underwent surgery were not consistently reported., Conclusion: Based on critical analysis of the clinical presentation of sinonasal sarcoidosis in our case series and on review of the literature, sinonasal sarcoidosis can be classified into four subgroups: atrophic, hypertrophic, destructive, and nasal enlargement. Each subgroup responds differently to treatment and has its own differential diagnosis. Surgery is only indicated for a select group of patients and the vast majority of patients benefit from medical management alone.

Little is known regarding the exact pathogenesis of sarcoidosis, but it is widely recognized that it affects multiple organs. The presentation and imaging features can be nonspecific, and this is the reason why it is a great mimic of other diseases. Diagnosis of sarcoidosis is often prompted initially by clinical suspicion. Imaging plays a crucial role in both detection and monitoring of disease process. This review is a case-based systemic approach looking at various systemic manifestation of the disease presenting real clinical encounters using various imaging modalities., (Copyright © 2014 Elsevier Inc. All rights reserved.)

In this review, representative types of granulomatous lymphadenitis (GLA) are described. GLA can be classified as noninfectious GLA and infectious GLA. Noninfectious GLA includes sarcoidosis and sarcoid-like reaction. The cause of sarcoidosis remains unknown, but it has good prognosis. Sarcoid-like reaction, which is considered to be a biological defense mechanism, is observed in regional lymph nodes with many underlying diseases. Infectious GLA can be classified as suppurative lymphadenitis (LA) and nonsuppurative LA. Suppurative LA generally shows follicular hyperplasia and sinus histiocytosis in the early phase. In tularemia and cat scratch disease, monocytoid B lymphocytes (MBLs) with T cells and macrophages contribute to the formation of granuloma. However, none of the epithelioid cell granulomas of Yersinia LA contains MBLs like in cat scratch disease. In addition, almost all have a central abscess in granulomas induced by Gram-negative bacteria. In terms of the lymph nodes, tularemia and cat scratch disease are apt to affect the axillary and cervical regions while Yersinia LA affects the mesenteric lymph node. Nonsuppurative LA includes tuberculosis and BCG-histiocytosis. These are induced by delayed allergic reaction of M. tuberculosis. Tuberculosis LA mainly appears in the cervical lymph node. Organisms are histologically detected by Ziehl-Neelsen staining in the necrotic area. Toxoplasmosis is also a nonsuppurative protozoan infection (Toxoplasma gondii). In toxoplasma LA, MBLs can also be seen, but round and organized, well-formed granulomas are not found in this disease. Furthermore, necrosis is not induced and there are no accompanying neutrophils, eosinophils and fibrosis. GLA described above is associated with characteristic histological findings. An accurate pathological diagnosis using the above findings can lead to precise treatment.

In this article the authors discuss the issues related to assessment of activity and severity of sarcoidosis, course and radiographic manifestations of this disease. Problems in defining of different forms of sarcoidosis resulted in suggestion of new version of classification.

Background: Both type I interferon (IFN), also known as IFN-α and tumor necrosis factor alpha (TNF-α) have been implicated in the pathogenesis of sarcoidosis. We investigated serum levels of these cytokines in a large multi-ancestral sarcoidosis population to determine correlations between cytokine levels and disease phenotypes., Methods: We studied serum samples from 98 patients with sarcoidosis, including 71 patients of African-American ancestry and 27 patients of European-American ancestry. Serum type I IFN was measured using a sensitive reporter cell assay and serum TNF-α was measured using a commercial ELISA kit. Clinical data including presence or absence of neurologic, cardiac, and severe pulmonary manifestations of sarcoidosis were abstracted from medical records. Twenty age-matched non-autoimmune controls were also studied from each ancestral background. Differences in cytokine levels between groups were analyzed with Mann-Whitney U test, and correlations were assessed using Spearman's rho. Multivariate logistic regression models were used to detect associations between cytokines and clinical manifestations., Results: Significant differences in cytokine levels were observed between African- and European-American patients with sarcoidosis. In African-Americans, serum TNF-α levels were significantly higher relative to matched controls (P = 0.039), and patients with neurologic disease had significantly higher TNF-α than patients lacking this manifestation (P = 0.022). In European-Americans, serum type I IFN activity was higher in sarcoidosis cases as compared to matched controls, and patients with extra-pulmonary disease represented a high serum IFN subgroup (P = 0.0032). None of the associations observed were shared between the two ancestral groups., Conclusions: Our data indicate that significant associations between serum levels of TNF-α and type I IFN and clinical manifestations exist in a sarcoidosis cohort that differ significantly by self-reported ancestry. In each ancestral background, the cytokine elevated in patients with sarcoidosis was also associated with a particular disease phenotype. These findings may relate to ancestral differences in the molecular pathogenesis of this heterogeneous disease.

Purpose: To validate the international criteria for the diagnosis of ocular sarcoidosis as proposed by the First International Workshop on Ocular Sarcoidosis (FIWOS)., Methods: A retrospective case-control study examined 370 consecutive uveitis patients at Tokyo Medical and Dental University Hospital. The study group consisted of 50 patients with biopsy-proven sarcoidosis and 320 control patients with other uveitis entities. Predictive values [sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV)] were calculated for seven clinical signs, five laboratory tests, and the diagnostic criteria., Results: With the exception of the liver enzyme tests, there was a significantly higher incidence of positive results for all clinical signs and laboratory tests in the biopsy-proven sarcoidosis patients than in the control uveitis patients. Although variability was noted in the predictive values of the seven clinical signs and five laboratory tests, the sensitivity, specificity, PPV, and NPV of the FIWOS criteria, which were based on the combined results of the clinical signs and laboratory tests, were 1.000, 0.956, 0.781, and 1.000, respectively., Conclusions: The FIWOS criteria have high predictive values for diagnosing ocular sarcoidosis. To further confirm these findings, an international prospective multicenter study should be undertaken in the future.

The major histocompatibility complex (MHC) class II transactivator (MHC2TA) is known as a master regulator for expression of MHC class II molecules. In the present study, we investigated the influence on the risk for sarcoidosis of two variants of the MHC2TA gene, selected from previous association studies of inflammatory diseases. Seven hundred and twenty-eight sarcoidosis patients and 873 controls matched by ethnicity were included in the study. Patients were classified as with Löfgren's syndrome (or not) as subphenotypes. Individuals were genotyped for two single nucleotide polymorphisms (SNPs) of the MHC2TA gene, rs3087456 A/G and rs11074932 C/T, and were human leukocyte antigen (HLA)-DRB1-typed. After correction for multiple testing, our data showed a significant association with Löfgren's syndrome in allelic model for the rs3087456 SNP, which was not detected in non-Löfgren's patients. A similar trend was noted for the rs11074932 SNP. These risk factors were independent of HLA-DRB1*03, which is known to be associated with Löfgren's syndrome. The finding of a new genetic association between Löfgren's syndrome and MHC2TA gene polymorphisms, which seems independent of HLA-DRB1*03 and relates to the expression of MHC class II molecules, strongly supports the idea that Löfgren's syndrome is a separate disease entity.

Sarcoidosis is a multisystemic disorder of unknown etiology, affecting primarily the lung and characterized by epithelioid granulomas. Disease association studies showed human leukocyte antigen (HLA) class II to be related to sarcoidosis. Initially, we studied the association of sarcoidosis with DQB1, and in the present study, we evaluated all amino acid variants of the HLA-DPB1, -DQB1, -DRB1, -DRB3, -DRB4 and -DRB5 genes to identify possible polymorphisms associated with the disease. Patients and controls were typed for class II genes to the allele level by sequence-based typing. Multiple logistic regression models showed DRAla71 and DQPhe9 to be independently associated with the disease. Subdivision of patients according to their radiographic stage resulted in identification of DRArg74 as independent associated residue in the RS I group, whereas DRAla71 and DQTyr30 were associated with RS II-IV groups. Polymorphic residues specifically associated with sarcoidosis shed new light on the characteristics of sarcoidosis-triggered peptides. Overall, pocket 9 of DQ and pocket 4 of DR seem to be the most important areas involved in the association with sarcoidosis.

Sarcoidosis is an immune system disorder characterised by non-necrotising granulomas. Pulmonary involvement is the most common presentation of sarcoidosis, but it can manifest in any organ. Other commonly involved organ systems include the lymph nodes (especially the intrathoracic nodes); the skin; the eyes; the liver; the heart; and the nervous, musculoskeletal, renal, and endocrine systems. The typical and atypical imaging features of multisystemic involvement of sarcoidosis have been discussed with review of the gamut of radiological manifestations of thoracic, cardiac, CNS, abdominal and musculoskeletal sarcoidosis.

The clinical assessment of sarcoidosis has been confounded by its inexact diagnostic criteria, multiorgan involvement, and effects of therapy. In this manuscript an instrument, the Sarcoidosis Three-Dimensional Assessment Instrument (STAI), is proposed to assess the clinical state of sarcoidosis. The instrument examines each organ involved with sarcoidosis separately. For each organ, the instrument contains three axes: involvement, severity, and activity. Involvement is based upon a previously described instrument that has been updated to capture involvement of more organs and to account for advances in diagnostic testing for sarcoidosis. Severity is based both on the decline from normal capacity as well as physical and psychosocial limitation. Disease activity takes into account changes in organ function as well as changes in therapy. Although this instrument is presently not validated, it is hoped that it will undergo study as it rationally accounts for several problems of previous assessment instruments.

Background: Skin is involved in 25% of cases of sarcoidosis. The lesions are specific and nonspecific depending on the presence or absence of granulomas, respectively. Specific lesions are not thought to have prognostic significance and are not associated with systemic disease., Objective: We sought to evaluate for the presence or absence of systemic disease in patients with subcutaneous sarcoidosis., Methods: With diagnostic criteria of subcutaneous sarcoidosis, 33 cases were identified in the literature and 21 cases in our institutional database. A retrospective clinical and pathologic review of these cases was conducted., Results: Subcutaneous sarcoidosis is characterized by a peak incidence during the fourth decade; female predisposition; asymptomatic to slightly tender lesions typically involving the upper extremities; cutaneous lesional clustering and multiplicity; autoimmune disease associations at time of diagnosis in a subset of cases; systemic disease associations at diagnosis in most patients, typically consisting of bilateral hilar adenopathy; and a favorable response to oral corticosteroid therapy., Limitations: Retrospective analysis with inadequate documentation of therapeutic regimens and their responses in some cases is a limitation of this study., Conclusions: The confirmatory diagnosis of subcutaneous sarcoidosis depends on identifying pannicular noninfectious sarcoidal or epithelioid granulomas with minimal lymphocytic inflammation. Subcutaneous sarcoidosis is the only specific subset of cutaneous sarcoidosis frequently associated with systemic disease.

Aim: This investigation was undertaken to clarify the current status of steroid therapy for cardiac sarcoidosis in Japan., Methods: A questionnaire survey was conducted throughout Japan concerning cases in which steroid therapy had been administered. Replies describing 52 cases (15 men, 37 women; mean age +/- SD, 59.8 +/- 14.5 years) were analyzed., Results: Of the 49 patients whose New York Heart Association (NYHA) functional classification was reported, 29 (55.8%) were in class I; 13 (25.0%) class II; 4 (7.7%) class III and 3 (5.8%) class IV. The most common initial steroid dose (used in 35 cases, or 67.3%) was 30 mg/day or 60 mg on alternate days. In most cases (85.4%), this dose was continued for 1 month followed by tapering by 5 mg every 2 to 4 weeks until reaching the maintenance dose of 5 to 10 mg/day. Steroid therapy was reported to result in improvement in 54%, no change in 40%, and deterioration in 6%., Conclusion: This nationwide questionnaire survey indicated fairly uniform patterns of steroid therapy for cardiac sarcoidosis in Japan, with clinical improvement in over one-half of cases and possible stabilization in most others.

Sarcoidosis is a multisystem disorder of unknown aetiology. Pathologically it is characterized by the presence of non-caseating epithelioid-cell granulomas in the lungs, intrathoracic lymph nodes and other affected organs. The clinical course of sarcoidosis is widely variable, ranging from asymptomatic but abnormal findings in chest radiography to progressive multiorgan disease, which leads to fibrosis with organ failure and functional impairment. The aim of this article is to familiarize physicians with clinical features and treatment of this disease.

Sarcoidosis is a multisystem granulomatous disease of unknown etiology. Almost any organs of the body, but mostly the lungs, are involved. Bone mineral density (BMD) can be affected directly or indirectly in chronic granulomatous systemic diseases such as sarcoidosis. The aim of our study was to evaluate BMD in premenopausal and postmenopausal sarcoidosis patients with or without prednisone treatment and to compare their BMD values with those of a control group having the same menopausal status. Thirty-five premenopausal women (18 untreated, 8 treated, and 9 controls) and 21 postmenopausal women (5 untreated, 5 treated, and 11 controls) were included in the study. All of the patients had a histologically proven diagnosis and were being followed-up at the Sarcoidosis Outpatient Clinic of our unit. BMD of the lumbar (L) spine and femoral neck was measured by dual-energy absorptiometry (DEXA). The subgroups of premenopausals and postmenopausals were compared separately. Comparison among the groups was performed by using analysis of variance. Age, duration of the disease, and body mass index were comparable in treated, untreated, and control subgroups of the pre- and postmenopausal groups, and the subgroups of postmenopausals had comparable durations since menopause. For premenopausals, BMD values at L1-4 were not significantly different among the subgroups (0.920 +/- 0.08 g/cm(2), 0.801 +/- 0.09 g/cm(2), and 0.910 +/- 0.05 g/cm(2), for untreated, treated, and controls, respectively). However, the BMD value at the femoral neck in treated patients (0.921 +/- 0.1 g/cm(2)) was significantly lower than the values in untreated patients (1.080 +/- 0.2 g/cm(2); P < 0.01) and in controls (1.028 +/- 0.17 g/cm(2); P < 0.05). For postmenopausals, the BMD value at L1-4 in controls (1.019 +/- 0.07 g/cm(2)) was significantly higher than the values in untreated patients (0.783 +/- 0.01 g/cm(2)) and in treated patients (0.751 +/- 0.08 g/cm(2); P < 0.001 for both). The BMD value at the femoral neck in controls (0.890 +/- 0.1 g/cm(2)) was higher than the values in untreated patients (0.745 +/- 0.08 g/cm(2)) and treated patients (0.747 +/- 0.1 g/cm(2)), but the difference was not statistically significant (P = 0.06). We concluded that sarcoidosis patients, especially postmenopausal patients with corticosteroid treatment, may have an increased risk of bone mineral loss. Large-scale studies are warranted in order to delineate the exact roles of the disease itself, menopausal status, and corticosteroid treatment in this bone mineral loss.

The frequency of skin involvement of sarcoidosis is 10-30% of all cases, but the prevalence of a particular type of cutaneous lesion varies among races as well as individual cases. Cutaneous involvement is divided into specific and nonspecific categories. Specific lesions include nodules, plaques, lupus pernio, subcutaneous nodules, and other rare manifestations as well as scar infiltrates. Despite the clinical importance of scar infiltrates in the diagnosis of sarcoidosis, it is often overlooked because the lesions are usually small and asymptomatic. There is some clinical importance of cutaneous sarcoidosis; the ease in obtaining lesional samples which enables a histological diagnosis of sarcoidosis, and the association of a particular type of cutaneous lesion with other organ involvement.

Sarcoidosis may be affected by sex, race, and age. A Case Control Etiologic Study of Sarcoidosis (ACCESS) enrolled 736 patients with sarcoidosis within 6 mo of diagnosis from 10 clinical centers in the United States. Using the ACCESS sarcoidosis assessment system, we determined organ involvement for the whole group and for subgroups differentiated by sex, race, and age (less than 40 yr or 40 yr and older). The study population was heterogeneous in terms of race (53% white, 44% black), sex (64% female, 36% male), and age (46% < 40 yr old, 54% > or = 40 yr old). Women were more likely to have eye and neurologic involvement (chi(2) = 4.74, p < 0.05 and chi(2) = 4.60, p < 0.05 respectively), have erythema nodosum (chi(2) = 7.28, p < 0.01), and to be age 40 yr or over (chi(2) = 6.07, p < 0.02) whereas men were more likely to be hypercalcemic (chi(2) = 7.38, p < 0.01). Black subjects were more likely to have skin involvement other than erythema nodosum (chi(2) = 5.47, p < 0.05), and eye (chi(2) = 13.8, p < 0.0001), liver (chi(2) = 23.3, p < 0.0001), bone marrow (chi(2) = 18.8, p < 0.001), and extrathoracic lymph node involvement (chi(2) = 7.21, p < 0.01). We conclude that the initial presentation of sarcoidosis is related to sex, race, and age.

There are four types of muscular sarcoidosis: nodular, chronic myopathy, acute myositis, and asymptomatic. The nodular type is important because it may be confused with a soft tissue tumor. Magnetic resonance (MR) imaging provides specific findings. A star-shaped central structure of decreased signal intensity, a "dark star" sign, is seen on the axial images. A long nodule with an inner stripe of decreased signal intensity and outer stripes of increased signal intensity, a "three stripes" sign, is seen on the coronal and sagittal images. In the chronic myopathy type, the role of MR imaging is limited. Gallium scintigraphy, which reflects activity of inflammation, may show increased uptake. In the acute myositis type, MR imaging shows increased signal intensity, and gallium scintigraphy shows increased uptake; however, these findings are nonspecific.

Sarcoidosis is a systemic granulomatous condition of unknown origin. It is defined by histological features of epithelioid and giant-cell granuloma without caseous necrosis. Skin manifestations are observed in 25% of the cases of sarcoidosis, sometimes appearing as the inaugural symptom. Although these skin disorders are not life threatening, they do have a major functional and/or esthetic impact and may require specific therapy using aggressive treatments. Recent progress in immunology and molecular biology is helpful in understanding interactions between monocyte-macrophages and T lymphocytes and the cytokine pattern implicated in the granulomatous reaction. Research concerning the agent(s) causing the focus of the immune response on the TH1 pathway may be helpful in developing promising immunomodulation therapies. The very unpredictable course of the disease explains the difficulties encountered in assessing therapeutic efficacy and the small number of controlled trials. General corticosteroid therapy remains the mainstay treatment for severe skin disorders in sarcoidosis. APS and local corticoid therapy can be useful when systemic corticosteroids are not needed or to achieve a steroid-sparing effect. Indications for methotrexate and new compounds such as thalidomide or certain antibiotics with an immunomodulator effect remain to be evaluated.

Imaging plays an important role in identifying thoracic, abdominal and neurological localizations of sarcoidosis as well as ENT and bone localizations. It contributes to disease detection and is helpful for diagnostic, prognostic and therapeutic decision making and useful for therapeutic monitoring. The chest x-ray is particularly important in the initial work-up and to follow well-tolerated disease. Other investigations, depending on the localization, are helpful to follow the course of severe or chronic sarcoidosis.

Many atypical forms of sarcoidosis have been described. mediastinum-lung involvement, observed in 90% of the cases, may cause atypical manifestations: hemoptysis, chest pain, predominant pleural or proximal bronchial involvement. Diffuse "unpolished glass" images or air cavities may be observed on the chest x-ray. A rigorous diagnostic work-up is necessary for these atypical forms. Pathological confirmation is mandatory: non-caseous tuberculoid granuloma. A very wide range of extra-thoracic localizations have been described with variable clinical manifestations. In cases with no mediastinum-lung involvement, pathology data must be confronted with the notion of multiple organ dissemination to reach diagnosis.

Purpose: To document the changes observed at sequential magnetic resonance (MR) imaging of sarcoidosis lesions of the central nervous system (CNS) during treatment with corticosteroids., Materials and Methods: The abnormalities detected in 24 patients (mean follow-up, 36 months) were compared before and after therapeutic periods (n = 75) that were divided into attack (high-dose), upkeep (decreased-dose), and minimal (low-dose) periods. Parenchymal lesions were classified as type 1 (enhanced with gadolinium), type 2 (demyelinating), or type 3 (lacunar) and were assessed as regressing, stable, or progressing., Results: Seven of the 24 patients had several types of lesions. Isolated type 3 lesions (six patients) were the only lesions not associated with neurologic deficit. Type 1 lesions (13 patients) regressed in 22 of 22 attack periods and progressed in nine of 27 upkeep and minimal periods. MR imaging depicted relapses in patients with multifocal CNS involvement or long-standing CNS impairment or in those who had previously received steroid therapy. Type 2 (seven patients) and type 3 (13 patients) lesions remained stable in 68 of 68 therapeutic periods. Type 1 lesions appeared in three patients with type 2 and type 3 lesions during two upkeep and three minimal periods. Findings at follow-up MR imaging contributed to the reintroduction of high-dose corticosteroid therapy in eight patients., Conclusion: MR imaging can be used to differentiate between reversible and irreversible lesions in CNS sarcoidosis. MR imaging can be a useful tool for adjusting treatment to prevent irreversible CNS damage.

The aim of this study was to analyze the association between HLA class I and class II DR frequency in the different stages of sarcoidosis in Polish population. 88 patients and 30 healthy controls have been typed. Patients were divided into three groups depending on radiological findings. In the first group were 28 cases presenting the regression of the disease. In the second were 33 patients in stable stage II or III and in the third group 27 patients with pulmonary fibrosis (stage IV). The typing was performed by NIH method using commercial sera. There were no statistically significant differences between studied group in HLA-A class I. The frequency of HLA B-18 was statistically more frequent in patients with sarcoidosis compared to healthy controls. HLA-DR1 was not present in third group of patients and the difference was significant compared to healthy controls.

Background: Sarcoidosis is a multiorgan granulomatous disease of unknown cause. Lack of an objective system for assessment of sarcoidosis to evaluate disease course and effectiveness of therapy is a major problem., Methods: The sarcoidosis assessment instrument was developed by the Steering Committee of A Case Control Etiologic Study of Sarcoidosis (ACCESS) which included investigators at the ten ACCESS Clinical Centers, the Clinical Coordinating Center, and representatives of the National Heart, Blood, and Lung Institute. This system was developed to assess sarcoidosis organ involvement in ACCESS patients who would be followed over a two-year period. The system represents a consensus of opinions of members of the Steering Committee based on review of their experience and the medical literature., Results: Criteria for involvement in patients with biopsy-confirmed sarcoidosis are presented for organs and systems that are commonly involved (lung, skin, eyes, liver, calcium metabolism), unusual but clinically important (nervous system, kidney, heart) and other sites (non-thoracic lymph nodes, bone marrow, spleen, bone/joint, ear/nose/throat, parotid/salivary glands, muscles)., Conclusion: The proposed instrument is partially subjective in that it depends upon the clinician's diligence in pursuing evidence for sarcoidosis involvement of various organs. It is hoped that this instrument will lead to increased standardization in the definition of sarcoidosis organ involvement to help clinicians and researchers better characterize patients with sarcoidosis.