Sarcoidosis Organ Research Articles

Pulmonary sarcoidosis: differences in lung function change over time

IntroductionGiven the heterogeneity of sarcoidosis, predicting disease course of patients remains a challenge. Our aim was to determine whether the 3-year change in pulmonary function differed between pulmonary function phenotypes...

From Karl Wurm and Guy Scadding's staging to 18F-FDG PET/CT scan phenotyping and far beyond: perspective in the evading history of phenotyping in sarcoidosis.

Sarcoidosis is an inflammatory granulomatous disease of unknown etiology involving any organ or tissue along with any combination of active sites, even the most silent ones clinically. The unpredictable nature of the sites involved in sarcoidosis dictates the highly variable natural history of the disease and the necessity to cluster cases at diagnosis based on clinical and/or imaging common characteristics in an attempt to classify patients based on their more homogeneous phenotypes, possibly with similar clinical behavior, prognosis, outcome, and therefore with therapeutic requirements. In the course of the disease's history, this attempt relates to the availability of a means of detection of the sites involved, from the Karl Wurm and Guy Scadding's chest x-ray staging through the ACCESS, the WASOG Sarcoidosis Organ Assessment Instruments, and the GenPhenReSa study to the 18F-FDG PET/CT scan phenotyping and far beyond to new technologies and/or the current "omics." The hybrid molecular imaging of the 18F-FDG PET/CT scan, by unveiling the glucose metabolism of inflammatory cells, can identify high sensitivity inflammatory active granulomas, the hallmark of sarcoidosis-even in clinically and physiologically silent sites-and, as recently shown, is successful in identifying an unexpected ordered stratification into four phenotypes: (I) hilar-mediastinal nodal, (II) lungs and hilar-mediastinal nodal, (III) an extended nodal supraclavicular, thoracic, abdominal, inguinal, and (IV) all the above in addition to systemic organs and tissues, which is therefore the ideal phenotyping instrument. During the "omics era," studies could provide significant, distinct, and exclusive insights into sarcoidosis phenotypes linking clinical, laboratory, imaging, and histologic characteristics with molecular signatures. In this context, the personalization of treatment for sarcoidosis patients might have reached its goal.

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.

Cardiac sarcoidosis outcome differences: A comparison of patients with de novo cardiac versus known extracardiac sarcoidosis at presentation

BackgroundSarcoidosis is a systemic disease characterized by granulomatous inflammation. Cardiac involvement is associated with increased morbidity. However, differences in clinical characteristics and outcomes based on initial sarcoidosis organ manifestation in patients with cardiac sarcoidosis (CS) have not been described. MethodsA retrospective cohort of 252 patients with CS at an urban, quaternary medical center was studied. Presentation, treatment and outcomes of de novo CS and prior ECS groups were compared. Survival free of primary composite outcome (left ventricular assist device implantation, orthotopic heart transplantation (OHT), or death) was assessed. ResultsThere were 124 de novo CS patients and 128 with prior ECS at time of CS diagnosis. De novo CS patients were younger at CS diagnosis (p = 0.020). De novo CS patients had a more advanced cardiac presentation: lower left ventricular ejection fraction (LVEF) (p < 0.001), more frequent sustained ventricular arrhythmias (VA) (p = 0.001), and complete heart block (p = 0.001). During follow-up, new VA (p < 0.001), ventricular tachycardia ablation (p < 0.001), and OHT (p = 0.003) were more common in the de novo CS group. Outcome free survival was significantly shorter for de novo CS patients (p = 0.005), with increased hazard of primary composite outcome (p = 0.034) and development of new VA (p = 0.027) when compared to ECS patients. Overall mortality was similar between groups. ConclusionPatients presenting with CS as their first recognized organ manifestation of sarcoidosis have an increased risk of adverse cardiac outcomes as compared to those with a prior history of ECS. Improved awareness and diagnosis of CS is warranted for earlier recognition.

Utility of electrophysiologic testing for sudden death risk stratification in cardiac sarcoidosis patients with mildly impaired left ventricular function

BackgroundVentricular arrhythmias (VA) account for at least 25% of deaths caused by cardiac sarcoidosis (CS) and may arise in patients with mildly impaired LVEF (>35%). ObjectiveIn the current study, we examine whether EP study may be used for sudden death risk stratification in CS patients who have mildly impaired LVEF and a diagnosis of highly probable or probable CS according to the World Association of Sarcoidosis and Other Granulomatous Diseases Sarcoidosis Organ Assessment Instrument (WASOGI). MethodsAll patients: (1) exhibited a diagnosis of highly probable or probable CS according to the WASOGI, (2) exhibited cardiac MRI findings consistent with CS, (3) exhibited LVEF >45% and (4) underwent EP study. Device interrogations, transmissions and medical records were reviewed for all patients. ResultsWe identified 46 CS patients with mildly impaired LVEF. VA were induced in 11 patients and 10/11 patients underwent ICD placement. Thirty-five patients had no VA and 24/35 patients underwent placement of an ILR. During the follow-up period, the VA event rate was 6.5%. The negative and positive predictive values of the EP study for the development of VA were 100% and 27.2%, respectively. ConclusionsIn CS patients with mildly impaired LVEF and a diagnosis of highly probable or probable CS, a negative EP study was highly predictive of the absence of VA. The successful execution of future prospective studies is contingent upon enrollment of phenotypically homogenous cardiac sarcoidosis patients.

Clinical characteristics and organ system involvement in sarcoidosis: comparison of the University of Minnesota Cohort with other cohorts

BackgroundSarcoidosis 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.MethodsWe 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.ResultsMean 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.ConclusionsThis 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.

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.

Comparing and Contrasting Guidelines for the Management of Cardiac Sarcoidosis.

Introduction: The Japanese Circulation Society (JCS) recently published new guidelines for the diagnosis and treatment of Cardiac Sarcoidosis (CS). There are two other guideline documents, the World Association of Sarcoidosis and Other Granulomatous Disorders Sarcoidosis Organ (WASOG) Assessment Instrument created in 1999 and updated in 2014. Also, in 2014, the Heart Rhythm Society (HRS) published their international guideline document. As co-chair of the HRS document I have been invited to compare and contrast the management aspects of the HRS guidelines with the new JCS document. Comments: (i) The HRS document recommended a stepwise approach to VT management and the JCS document is somewhat similar; but with some key differences. (ii) The HRS statement suggested that an ICD for CS patients with an indication for a pacemaker "can be useful". The JCS document take a similar position although with some additional criteria related to National Health Institute Coverage guidelines. (iii) Both HRS and the JCS documents agree that ICDs are recommended in patients with general guideline indications for primary prevention (i.e. LVEF less than 35%). However which additional patients should be considered for ICDs is controversial. The 2016 JCS document is broadly similar, with the major exception that it is recommended that all patients with LVEF 35-50% should have an EP study. Conclusion: The Japanese have been leaders in many aspects of CS including in guideline development. It is clear that the future of CS management is bright, with increasing international collaborations and also multiple efforts underway to obtain higher quality data to inform future guidelines.

Sarcoidosis Developing During Secukinumab Therapy: Case Report

Introduction: Sarcoidosis is a systemic granulomatous inflammatory disease with an unknown etiology and complex pathogenesis. Existing literature supports the relationship of new-onset sarcoidosis with the use of a several biologic agents. Since the skin is the second most commonly involved organ in sarcoidosis and often precedes systemic involvement, dermatologists must be able to recognize its non-specific clinical presentation.Case Report: We present a 45 year old female with psoriatic arthritis who developed biopsy proven cutaneous sarcoidal granulomas with pulmonary involvement shortly after initiating secukinumab for treatment of psoriatic arthritis. Despite discontinuation of secukinumab, the sarcoidosis has persisted.Discussion: This is the first case report of secukinumab, or any IL-17 inhibitor related sarcoidosis that we are aware of in the literature. Dermatologists should be aware of this as a possible side effect of secukinumab use. As the research on the role of IL-17 in the pathogenesis of sarcoidosis continues to develop, the implications of this side effect of IL-17 inhibition may have important future implications.

Sarcoidosis Developing During Secukinumab Therapy: Case Report

Introduction: Sarcoidosis is a systemic granulomatous inflammatory disease with an unknown etiology and complex pathogenesis. Existing literature supports the relationship of new-onset sarcoidosis with the use of a several biologic agents. Since the skin is the second most commonly involved organ in sarcoidosis and often precedes systemic involvement, dermatologists must be able to recognize its non-specific clinical presentation.Case Report: We present a 45 year old female with psoriatic arthritis who developed biopsy proven cutaneous sarcoidal granulomas with pulmonary involvement shortly after initiating secukinumab for treatment of psoriatic arthritis. Despite discontinuation of secukinumab, the sarcoidosis has persisted.Discussion: This is the first case report of secukinumab, or any IL-17 inhibitor related sarcoidosis that we are aware of in the literature. Dermatologists should be aware of this as a possible side effect of secukinumab use. As the research on the role of IL-17 in the pathogenesis of sarcoidosis continues to develop, the implications of this side effect of IL-17 inhibition may have important future implications.

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.

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.

Diagnosis and treatment of hepatic sarcoidosis

The presence of granulomas in the liver raises consideration of a wide differential diagnosis, but in most Western series, sarcoidosis accounts for a majority of cases. This review will focus specifically on the diagnosis of and therapy for hepatic sarcoidosis. Sarcoidosis is a systemic granulomatous disease of unknown etiology. Hepatic involvement of sarcoidosis was described in 11.5% of 736 patients enrolled in the ACCESS study. However, presence alone of granulomas in an organ in sarcoidosis does not dictate treatment. The decision to treat should be based on symptoms and severity of disease. Although hepatic involvement usually is asymptomatic, a minority of patients progress to chronic cholestatic disease, portal hypertension, and cirrhosis that may require liver transplantation. Treatment of hepatic sarcoidosis should be reserved for patients who manifest this spectrum of disease. Glucocorticoid treatment is first-line therapy for hepatic sarcoidosis, improving symptoms and abnormal laboratory values but generally having no effect on progression of disease. In addition to glucocorticoids, immunomodulators such as azathioprine, methotrexate, hydroxychloroquine, and infliximab have been used with some positive effects on symptoms, liver enzyme abnormalities, and hepatomegaly, but none has been shown to prevent progression of disease. Ultimately, in cases of overt liver failure, liver transplantation is the definitive treatment. Overall, treatment for hepatic sarcoidosis is targeted toward alleviation of symptoms but has no curative potential at this time. Focus should be on discovering the etiology of the disease to target therapy at prevention, not cure.

Pulmonary sarcoidosis: Radiographic features

Lungs are the most commonly affected organ in sarcoidosis. More than 90% of the patients have an abnormal chest roentgenogram at some stage of their illness. Radiologic abnormalities often are the first to suggest the diagnosis of sarcoidosis.