Organ Involvement In Sarcoidosis Research Articles

Organ involvement in newly diagnosed sarcoidosis patients in the Netherlands: The first large European multicentre prospective study

BackgroundClinical presentation and prevalence of organ involvement is highly variable in sarcoidosis and depends on ethnic, genetic and geographical factors. These data are not extensively studied in a Dutch population. AimTo determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands. MethodsTwo large Dutch teaching hospitals participated in this prospective cohort study. All adult patients with newly diagnosed sarcoidosis were prospectively included and a standardized work-up was performed. Organ involvement was defined using the WASOG instrument. ResultsBetween 2015 and 2020, a total of 330 patients were included, 55% were male, mean age was 46 (SD 14) years. Most of them were white (76%). Pulmonary involvement including thoracic lymph node enlargement was present in 316 patients (96%). Pulmonary parenchymal disease was present in 156 patients (47%). Ten patients (3%) had radiological signs of pulmonary fibrosis. Cutaneous sarcoidosis was present in 74 patients (23%). Routine ophthalmological screening revealed uveitis in 29 patients (12%, n = 256)). Cardiac and neurosarcoidosis were diagnosed in respectively five (2%) and six patients (2%). Renal involvement was observed in 11 (3%) patients. Hypercalcaemia and hypercalciuria were observed in 29 (10%) and 48 (26%, n = 182) patients, respectively. Hepatic involvement was found in 6 patients (2%). In 30% of the patients, systemic immunosuppressive treatment was started at diagnosis. ConclusionsHigh–risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.

Sarcoidosis and frailty: recognizing factors that foster holistic resilience.

Sarcoidosis is a multiorgan system disease exerting significant impact on biophysical, social, psychological and emotional well-being. Mortality and disability correlate to accessible, timely, expert care for sarcoidosis and its related complications. Across health conditions, positive healthcare interactions and interventions can rehabilitate unfavourable factors tied to concepts of 'frailty'. Here, we set out to introduce concepts related to frailty and their impact in the context of sarcoidosis. Studies examining frailty across other multiorgan and single organ-based diseases that mirror organ involvement in sarcoidosis demonstrate findings that bear relevance in sarcoidosis. Namely, factors predisposing a person to frailty are a multifactorial phenomenon which are also reflected in the lived experience of sarcoidosis; and that early diagnosis, intervention and prevention may alter a course towards more favourable health outcomes. Factors predisposing to frailty in other health conditions may also signal a risk in sarcoidosis. In turn, proactive health preservation - regardless of age - may lead to improved biopsychosocial reserve and health-related quality of life. Fortifying holistic resilience in sarcoidosis is anticipated to reduce risk of the occurrence and prolongation of health-related complications, and facilitate swifter recovery from biophysical complications as well as from psychosocial and emotional stressors.

Rare organ manifestations of sarcoidosis

PurposeWe retrospectively analyzed the frequency and clinical characteristics of organs rarely involved with sarcoidosis in a cohort of 1158 sarcoidosis patients cared for over nearly 11 years in a university outpatient sarcoidosis clinic. MethodsData were analyzed from an institution-approved sarcoidosis clinical database containing demographic and clinical characteristics of sarcoidosis outpatients cared for between May 2011 and March 2021 at a university medical center sarcoidosis clinic. The diagnosis of sarcoidosis was established by standard international criteria. Rare organ involvement was defined as an organ not individually listed in the Word Association of Sarcoidosis and Other Granulomatous Disorders Sarcoidosis Organ Assessment Instrument. ResultsTwenty-six of the 1158 patients (2.2%) had 27 instances of rare organ involvement. The most common rare organ involved was the GI tract, followed by the testicle and then the female reproductive tract. Only 1 of the 26 patients with rare sarcoidosis organ involvement required therapy for that organ involvement. In comparison with sarcoidosis patients without rare organ involvement, patients with rare organ involvement were more likely to be black, have more total organs involved with sarcoidosis, and more likely require anti-sarcoidosis therapy at some point during the course of their disease. There were no differences between these groups in terms of sex, age at diagnosis, and most recent percent predicted forced vital capacity. ConclusionsRare sarcoidosis organ involvement occurred in 2.2 percent of this cohort. Although rare organ involvement rarely required treatment, it was associated with more extensive disease that was more likely to require therapy.

Associations between occupational and environmental exposures and organ involvement in sarcoidosis: a retrospective case-case analysis

BackgroundSarcoidosis most commonly affects lungs and intrathoracic lymph nodes, but any other organ can be involved. In epidemiological studies, many occupational and environmental exposures have been linked to sarcoidosis but their relationship with the disease phenotype has barely been studied.ObjectiveTo investigate how occupational and environmental exposures prior to diagnosis relate to organ involvement in patients with sarcoidosisMethodsWe retrospectively studied patients seen at a sarcoidosis clinic between 2017 and 2020. Patients were included if they had a clinical presentation consistent with sarcoidosis and histologically confirmed epithelioid granulomas or had Löfgren syndrome. In a case–case analysis using multivariable logistic regression we calculated odds ratios (OR) of prespecified exposure categories (based on expert ascertainment) for cases with a given organ involvement versus cases without this organ involvement.ResultsWe included 238 sarcoidosis patients. Sarcoidosis limited to pulmonary involvement was associated with exposure to inorganic dust prior to diagnosis (OR 2.11; 95% confidence interval [CI] 1.11–4.17). Patients with liver involvement had higher odds of contact with livestock (OR 3.68; 95% CI 0.91–12.7) or having jobs with close human contact (OR 4.33; 95% CI 1.57–11.3) than patients without liver involvement. Similar associations were found for splenic involvement (livestock: OR 4.94, 95% CI 1.46–16.1; close human contact: OR 3.78; 95% CI 1.47–9.46). Cardiac sarcoidosis was associated with exposure to reactive chemicals (OR 5.08; 95% CI 1.28–19.2) or livestock (OR 9.86; 95% CI 1.95–49.0). Active smokers had more ocular sarcoidosis (OR 3.26; 95% CI 1.33–7.79).ConclusionsOur study indicates that, in sarcoidosis patients, different exposures might be related to different organ involvements—hereby providing support for the hypothesis that sarcoidosis has more than one cause, each of which may promote a different disease phenotype.

Diagnostic utility of 68Ga-citrate and 18FDG PET/CT in sarcoidosis patients.

Sarcoidosis is a chronic granulomatous disease of unknown etiology. The disease most commonly involves the lungs and the mediastinal lymph nodes while extrapulmonary organs such as the skin, eye, liver or spleen may also be comprised. Many imaging modalities have been used for the clinical evaluation of sarcoidosis patients but all have been found to have certain drawbacks for a reliable identification assessment due to the equivocal diagnostic results. This case series was designed to determine the clinical trenchancy of simultaneous 68Ga citrate PET/CT [Positron emission tomography with 68Ga citrate (68Ga citrate PET/CT)] and 18F-FDG PET/CT [Positron emission tomography with 2-deoxy-2-[fluorine-18] fluoro-D-glucose integrated with computed tomography (18F-FDG PET/CT)] imaging in sarcoidosis patients. The main goal of the study was to evaluate sarcoidosis with respect to disease activity and organ involvement. A total of eight sarcoidosis patients with a comorbid disease suspicion were included in the study. Conventional clinical parameters used for the diagnosis and the activity of sarcoidosis including CT [Computed tomography (CT)] were compared with the 68Ga-citrate PET/CT findings. Concurrent 18F-FDG PET/CT was performed to verify the granulomatous inflammation of sarcoidosis and to determine coexisting malignant or other inflammatory diseases. Our study results revealed that 68Ga citrate PET/CT imaging appears to be highly useful for the diagnosis, activity assessment and extrapulmonary organ involvement in sarcoidosis. Another crucial finding was the detection of extrapulmonary organ disease that are exceptionally involved, almost inaccessible by biopsy and that could not be otherwise displayed by other conventional imaging modalities. The third hallmark was the identification of a clinically asymptomatic and occult malignancy accompanying sarcoidosis that would not be revealed in any way if synchronous 18FDG PET/CT had not been performed. Simultaneous application of 68Ga citrate and 18FDG PET/CT may provide extremely useful data for the clinical evaluation of sarcoidosis patients in terms of the primary disease diagnosis, activity state, extrapulmonary organ involvement unachievable for biopsy and the clinically occult malignant disorders.

Association of Medication Adherence and Clinical Outcomes in Sarcoidosis

Sarcoidosis, one of the most common interstitial lung diseases, has significant health disparities. Approximately 50%of individuals affected with sarcoidosis will undergo spontaneous remission, but those who do not undergo remission often require long-term or lifelong treatment to prevent disease progression. We sought to assess the association between medication adherence and clinical outcomes in sarcoidosis. Adult patients in the Johns Hopkins Sarcoidosis Clinic diagnosed with pulmonary sarcoidosis on treatment were eligible for enrollment. Questionnaires were administered to assess medication adherence, health-related quality of life (HRQoL), health-care utilization, and sociodemographic information. Clinical information was abstracted from medical charts including lung function, disease duration, comorbidities, and sarcoidosis organ involvement. A total of 117 participants were enrolled (57%women; 55%black; median age, 57 years). Within the cohort, 66%of individuals reported at least one nonadherent behavior. Higher medication adherence was associated with better HRQoL (P<.05). There was no association between medication adherence and the odds of health-care utilization, FVC %predicted, FEV1 %predicted, or diffusion capacity of the lungs for carbon monoxide %predicted. Black participants reported lower medication adherence than white participants (P< .05). This is the first observational study of medication adherence in sarcoidosis. We found that higher medication adherence was associated with better HRQoL, with blacks more likely to report nonadherence. Medication adherence may be an important target to improve patient-reported outcomes and health disparities in sarcoidosis.

Phenotypes of organ involvement in sarcoidosis.

Sarcoidosis is a highly variable, systemic granulomatous disease of hitherto unknown aetiology. The GenPhenReSa (Genotype-Phenotype Relationship in Sarcoidosis) project represents a European multicentre study to investigate the influence of genotype on disease phenotypes in sarcoidosis.The baseline phenotype module of GenPhenReSa comprised 2163 Caucasian patients with sarcoidosis who were phenotyped at 31 study centres according to a standardised protocol.From this module, we found that patients with acute onset were mainly female, young and of Scadding type I or II. Female patients showed a significantly higher frequency of eye and skin involvement, and complained more of fatigue. Based on multidimensional correspondence analysis and subsequent cluster analysis, patients could be clearly stratified into five distinct, yet undescribed, subgroups according to predominant organ involvement: 1) abdominal organ involvement, 2) ocular-cardiac-cutaneous-central nervous system disease involvement, 3) musculoskeletal-cutaneous involvement, 4) pulmonary and intrathoracic lymph node involvement, and 5) extrapulmonary involvement.These five new clinical phenotypes will be useful to recruit homogenous cohorts in future biomedical studies.

Age-related and historical changes in the clinical characteristics of sarcoidosis in Japan

National surveys conducted in Japan between 1960 and 2004 suggest a gradually increasing incidence of sarcoidosis in women >50 years old with increased involvement of the eye, skin, and heart. However, whether this involvement is due to the increased age at diagnosis is still unclear. We aimed here to identify the age-related differences in organ involvement in sarcoidosis in Japan, as well as the historical changes in clinical characteristics and the age-specific distribution of cases at diagnosis. We reviewed 588 consecutive Japanese patients newly diagnosed with sarcoidosis between 1974 and 2012 at Jichi Medical University Hospital. We compared organ involvement between subgroups differentiated by sex and age (<45 years; n=275; ≥45 years; n=313) at diagnosis and identified historical changes in the age-specific distribution in 10-year intervals. Younger patients had more common involvement of extrathoracic lymph nodes, parotid/salivary gland, and liver, while older patients had more common involvement of non-lymphatic extrathoracic organs such as the eye, heart, muscle, and kidney. The age at diagnosis has consistently increased over the past four decades. The monophasic distribution in men has tended to become biphasic, and the biphasic distribution in women monophasic. Increasing trends were apparent for hypercalcemia and involvement of the gastrointestinal tract, skin, nervous system, muscle, and kidney. Elderly patients at diagnosis had various extrathoracic involvement including eye, skin, and cardiac lesions. Moreover, the age at diagnosis of sarcoidosis has continued to increase in both sexes, influencing the recent trends in clinical characteristics.

The Clinical Features of Sarcoidosis: A Comprehensive Review.

Sarcoidosis has innumerable clinical manifestations, as the disease may affect every body organ. Furthermore, the severity of sarcoidosis involvement may range from an asymptomatic state to a life-threatening condition. This manuscript reviews a wide variety of common and less common clinical characteristics of sarcoidosis. These manifestations are presented organ by organ, although additional sections describe systemic and multiorgan presentations of sarcoidosis. The lung is the organ most commonly involved with sarcoidosis with at least 90 % of sarcoidosis patients demonstrating lung involvement in most series. The skin, eye, liver, and peripheral lymph node are the next most commonly clinically involved organs in most series, with the frequency of involvement ranging from 10 to 30 %. The actual frequency of sarcoidosis organ involvement is probably much higher as it is frequently asymptomatic and may avoid detection. This is particularly common with lung, liver, cardiac, and bone involvement. Cardiac sarcoidosis is present in 25 % of all sarcoidosis but only causes clinical problems in 5 % of them. Nevertheless, unlike sarcoidosis involvement of most other organs, it may be suddenly fatal. Therefore, it is important to screen for cardiac sarcoidosis in all sarcoidosis patients. All sarcoidosis patients should also be screened for eye involvement as asymptomatic patients may have eye involvement that may cause permanent vision impairment. Pulmonary fibrosis from sarcoidosis is usually slowly progressive but may be life-threatening because of the development of respiratory failure, pulmonary hypertension, or hemoptysis related to a mycetoma or bronchiectasis. Some manifestations of sarcoidosis are not organ-specific and probably are the result of a release of mediators from the sarcoid granuloma. Two such manifestations include small fiber neuropathy and fatigue syndromes, and they are observed in a large percentage of patients.

Utility of FDG-PET-CT scanning in assessing the extent of disease activity and response to treatment in sarcoidosis.

Background:Radionuclide imaging modalities have increasingly been evaluated in the assessment of organ involvement in sarcoidosis. Fluoro-deoxyglucose positron emission tomography–computed tomography (FDG–PET–CT) scanning has received increasing attention in the recent years. The aim of our study was to evaluate the utility of FDG–PET–CT in determining the extent of organ involvement and disease activity in patients of sarcoidosis and to assess its utility in the evaluation of response to therapy. The secondary objective was to compare the agreement between clinical, radiological (HRCT) and metabolic indices (FDG–PET–CT) of disease activity.Materials and Methods:This was a prospective observational study conducted between March 2007 and December 2008 at a tertiary care referral center in north India. Twenty-five symptomatic and histopathologically proven cases of sarcoidosis underwent FDG–PET–CT scanning at baseline and a follow-up scan in 21 patients at 6-9 months post-treatment with glucocorticoids.Results:FDG–PET–CT scan detected metabolic disease activity in 24 of the 25 patients with clinically active sarcoidosis. It also demonstrated many clinically inapparent sites of disease activity. Complete or partial metabolic response was seen in 17 of the 21 patients in whom a follow-up scan was available. Substantial degree of agreement was found between the metabolic response and the radiological response, whereas moderate agreement was found between clinical and metabolic responses.Conclusions:FDG–PET–CT scanning is a useful imaging modality to assess disease activity, extent of disease involvement and response to treatment in clinically active sarcoidosis. There is substantial agreement between the HRCT and metabolic parameters of disease activity. Further, large sample size studies are proposed in order to identify the subset of patients who are likely to benefit the most from this sensitive modality of imaging, especially in developing countries where the cost of the procedure is an important concern.

Isolated Neurosarcoidosis

Neurosarcoidosis occurs in the central or peripheral nervous system and is usually associated with other sarcoidosis organ involvement. However, when sarcoidosis develops exclusively in the nervous system, its diagnosis is problematic. Retrospective analysis of patients who were histologically diagnosed with neurosarcoidosis without other organ involvement (isolated neurosarcoidosis) at Medical University of South Carolina and Allegheny General Hospital. For comparison, we also collected data from neurosarcoidosis patients with histologic evidence in an extraneural organ (systemic neurosarcoidosis). Ninety-one cases of neurosarcoidosis were identified with 10 patients having isolated neurosarcoidosis. Common clinical manifestations of the isolated neurosarcoidosis patients were headache (9), paresthesia (5), and cranial neuropathies (4). All isolated neurosarcoidosis patients underwent a biopsy from the central nervous system. The prebiopsy impression included lymphoma (4), tumor (2), and sarcoidosis (2). In all patients, no extranueral sarcoidosis developed during a relatively long follow-up period (mean 58 mo). Compared with the systemic neurosarcoidosis cohort (60), isolated neurosarcoidosis patients had similar demographics and neurological manifestations with a few exceptions including a more common frequency of headache, hemiparesis, and radiculopathy, leptomeningeal involvement on brain MRI, increased cell count in cerebrospinal fluid, and a more favorable clinical outcome (P<0.05). The duration of follow-up and the number of studies performed to evaluate patients for extraneural sarcoidosis were similar in the 2 cohorts. The clinical and radiologic features of isolated neurosarcoidosis are similar to those of systemic neurosarcoidosis with a few exceptions. The diagnosis of isolated neurosarcoidosis is problematic and often not considered before biopsy of neural tissue.

Imaging the inflammatory activity of sarcoidosis

Accurate assessment of pulmonary and extrapulmonary organ involvement in sarcoidosis is one of the great challenges for clinicians. This assessment includes the evaluation of symptoms and of sarcoidosis activity in a specific organ and its functional consequences. In this review, radiological and nuclear techniques to image the inflammatory activity of sarcoidosis are described, in particular (18)F-FDG positron emission tomography/computed tomography. The current use of this technique in clinical practice is explained, particularly in patients with persistent symptoms, stage IV disease and cardiac sarcoidosis.

Variation in the Lymphotoxin-α/Tumor Necrosis Factor Locus Modifies Risk of Erythema Nodosum in Sarcoidosis

Sarcoidosis is a multi-system inflammatory disease with organ involvement that varies by race and sex. Family studies indicate that genes play a role in the etiology and extent of organ involvement in sarcoidosis. In this study, we evaluated whether 25 variants distributed in 19 genes with a known role in inflammation were associated with erythema nodosum status in 659 sarcoidosis patients and 658 controls from A Case-Control Etiologic Study of Sarcoidosis (ACCESS). We found no association with affectation status; however, a variant in the promoter of tumor necrosis factor (TNF) at position -308 was found to be associated with erythema nodosum in Caucasian sarcoidosis patients (study-wide P=0.027). When separated by sex, a variant in intron 1 of lymphotoxin-alpha (LTA), a gene adjacent to TNF, was associated with erythema nodosum in female Caucasian sarcoidosis patients (study-wide P=0.027). These DNA variants frequently occur together in Caucasians, and each variant has individually been associated with erythema nodosum in sarcoidosis patients. These results confirm that variation in the LTA/TNF gene cluster modifies a major skin manifestation of sarcoidosis and may explain the higher rate of erythema nodosum in females with sarcoidosis.

Transforming growth factor-beta gene polymorphism in sarcoidosis and tuberculosis patients.

Transforming growth factor-beta (TGF-beta) plays an important role in many diseases, influencing as it does such processes as immune responses, fibrosing processes, and angiogenesis. Recently, polymorphisms have been described for TGF-beta that are associated with the risk of several diseases. In this study, we investigated whether TGF-beta 1 polymorphism has an effect on sarcoidosis and tuberculosis. TGF-beta 1 Codon 10 T869C polymorphism was investigated in 110 healthy control subjects, 104 sarcoidosis patients, and 101 tuberculosis patients. The TGF-beta genotype was determined using polymerase chain reaction restriction fragment length polymorphism. We found no significant differences in TGF-beta genotypes between sarcoidosis patients and healthy controls or tuberculosis patients and controls. The long axis of the tuberculin skin test was larger in the CC type compared with the CT type. However, there was no association between the TGF-beta genotype and the roentgenographic stage, the disappearance of shadows, or organ involvement in sarcoidosis, nor any association between genotype, the extent or type of roentgenographic shadow, or detected volume of tubercle bacilli in tuberculosis. From the results, we believe that TGF-beta polymorphisms on the whole do not have a strong influence on disease onset or clinical progression in sarcoidosis and tuberculosis, although this polymorphism might have an effect on the immune response in a tuberculosis host.