Hepatic Sarcoidosis Found Incidentally in a Patient Presenting With Recurrent Clostridium difficile Infections.

A 50-year-old female who presented to our hospital for recurrent diarrhea was found to have worsening aminotransferase and alkaline phosphatase levels. Workup revealed lymphadenopathy and hepatomegaly prompting a biopsy of the liver and axillary lymph node, confirming a diagnosis of hepatic sarcoidosis. Our patient later developed cutaneous sarcoidosis. She is currently asymptomatic and is followed by gastroenterology, pulmonary, and dermatology. Recognition of extrapulmonary manifestations of sarcoidosis is important for proper management of patients. Treatment often requires a multidisciplinary approach when more than one organ system is involved.

A Case of Cardiomyopathy Associated with CD36 Deficiency: Role of 18F-Fluorodeoxyglucose Positron Emission Tomography in the Diagnosis.

We herein report a patient with type I CD36 deficiency. The patient was initially suspected of having isolated cardiac sarcoidosis based on the presence of non-sustained ventricular tachycardia, delayed myocardial enhancement on magnetic resonance imaging (MRI), and diffuse accumulation of 18F-fluorodeoxyglucose (18F-FDG) on cardiac positron emission tomography (PET). Our findings suggest that the diagnosis of cardiomyopathy associated with CD36 deficiency is often missed, highlighting the importance of a differential diagnosis of isolated cardiac sarcoidosis.

CHARACTERISTICS AND OUTCOMES OF HOSPITALISED PATIENTS WITH HEART FAILURE AND SARCOIDOSIS: A PROPENISTY-MATCHED ANALYSIS OF THE NATIONWIDE READMISSIONS DATABASE 2010-2019.

BACKGROUND: Sarcoidosis is associated with a poor prognosis. There is a lack of data examining the outcomes and readmission rates of sarcoidosis patients with heart failure (SwHF) and without heart failure (SwoHF). We aimed to compare the impact of non-ischemic heart failure on outcomes and readmissions in these two groups. METHODS: The US Nationwide Readmission Database was queried from 2010-2019 for SwHF and SwoHF patients identified using the International Classification of Diseases, Ninth and Tenth Editions. Those with ischemic heart disease were excluded, and both cohorts were propensity matched for age, gender, and Charlson Comorbidity Index (CCI). Clinical characteristics, length of stay, adjusted healthcare-associated costs, 90-day readmission and mortality were analyzed. RESULTS: We identified 97,961 hospitalized patients (median age 63 years, 37.9% male) with a diagnosis of sarcoidosis (35.9% SwHF vs. 64.1% SwoHF). On index admission, heart failure patients had higher prevalences of atrioventricular block (3.3% vs. 1.4%, p<0.0001), ventricular tachycardia (6.5% vs. 1.3%, p<0.0001), ventricular fibrillation (0.4% vs. 0.1%, p<0.0001) and atrial fibrillation (22.1% vs. 7.5%, p<0.0001). SwHF patients were more likely to be readmitted (hazard ratio 1.28, p<0.0001), had higher length of hospital stay (5 vs. 4 days, p<0.0001), adjusted healthcare-associated costs ($9,667.0 vs. $9,087.1, p<0.0001) and mortality rates on readmission (5.1% vs. 3.8%, p<0.0001). Predictors of mortality included heart failure, increasing age, male sex, higher CCI and liver disease. CONCLUSION: SwHF is associated with higher rates of arrhythmia at index admission, as well as greater hospital cost, readmission and mortality rates compared to those without heart failure.

Arrhythmic Manifestations and Outcomes of Definite and Probable Cardiac Sarcoidosis.

BACKGROUND: The 2014 HRS consensus statement defines histological (definite) and clinical (probable) diagnostic categories of cardiac sarcoidosis (CS), but few studies have compared their arrhythmic phenotypes and outcomes. OBJECTIVE: Evaluate the electrophysiologic/arrhythmic phenotype and outcomes of patients with definite and probable CS. METHODS: We analyzed the arrhythmic/electrophysiologic phenotype in a single-center North American cohort of 388 patients (median age 56 years, 39% female) diagnosed with definite (n=58) or probable (n=330) CS (2000-2022). The primary composite outcome was survival to first ventricular tachycardia/fibrillation (VT/VF) or sudden cardiac death (SCD). Key secondary outcomes were also assessed. RESULTS: At index evaluation, in situ cardiac implantable electronic devices and antiarrhythmic drug use were more common in definite CS. At median follow-up 3.1 years, the primary outcome occurred in 22 (38%) definite and 127 (38%) probable CS patients (log-rank p=0.55). In multivariable analysis, only higher 18F-FDG SUVmax myocardium:SUVmax blood pool ratio (HR 1.09 [95% CI 1.03, 1.15], p=0.003, per 1 unit increase) was associated with the primary outcome. During follow-up, definite CS patients had higher burden of device-treated VT/VF events (mean 2.86 vs 1.56 per patient-year) and higher rate of progression to heart transplant/left ventricular assist device implantation, but no difference in all-cause mortality compared to probable CS patients. CONCLUSION: Definite and probable CS patients had similarly high risks of first sustained VT/VF/SCD and all-cause death though definite CS patients had a higher overall arrhythmic burden. Both CS diagnostic groups as defined by the 2014 HRS criteria require an aggressive approach to prevent arrhythmic complications.

Impact of Sarcoidosis on In-hospital Outcomes Among Patients with Atrial Fibrillation: A Nationwide Readmissions Database Analysis.

Sarcoidosis is a disease that involves multiple organs, including the cardiovascular system. While cardiac sarcoidosis has been increasingly recognized, the impact of sarcoidosis on atrial fibrillation (AF) is not well established. This study aimed to analyze the impact of sarcoidosis on in-hospital outcomes among patients who were admitted for a primary diagnosis of AF. Using the all-payer, nationally representative Nationwide Readmissions Database, our study included patients aged ≥18 years who were admitted for AF between 2017-2020. We stratified the cohort into two groups depending on the presence of sarcoidosis diagnosis. The in-hospital outcomes were assessed between the two groups via propensity score analysis. A total of 1031 (0.27%) AF patients with sarcoidosis and 387,380 (99.73%) AF patients without sarcoidosis were identified in our analysis. Our propensity score analysis of 1031 (50%) patients with AF and sarcoidosis and 1031 (50%) patients with AF but without sarcoidosis revealed comparable outcomes in early mortality (1.55% vs. 1.55%, P = 1.000), prolonged hospital stay (9.51% vs. 9.70%, P = .874), non-home discharge (7.95% vs. 9.89%, P = .108), and 30-day readmission (13.29% vs. 13.69%, P = .797) between the two groups. The cumulative cost of hospitalization was also similar in both groups ($12,632.25 vs. $12,532.63, P = .839). The in-hospital adverse event rates were comparable in both groups. Sarcoidosis is not a risk factor for poorer in-hospital outcomes following AF admission. These findings provide valuable insights into the effectiveness of the current guideline for AF management in patients with concomitant sarcoidosis and AF.

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

BACKGROUND: Clinical 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. AIM: To determine the prevalence of organ involvement and the indication for systemic immunosuppressive therapy in newly diagnosed sarcoidosis patients in the Netherlands. METHODS: Two 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. RESULTS: Between 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. CONCLUSIONS: High-risk organ involvement in sarcoidosis is uncommon at diagnosis. Indication for systemic immunosuppressive therapy was present in a minority of patients.

Sarcoidosis-Associated Pulmonary Hypertension.

Sarcoidosis-associated pulmonary hypertension (SAPH) is a very severe complication of the disease, largely impacting its morbidity and being one of its strongest predictors of mortality. With the recent modifications of the hemodynamic definition of pulmonary hypertension (mean arterial pulmonary pressure >20 instead of <25 mmHg,) its prevalence is presently not precisely known, but it affects from 3 to 20% of sarcoid patients; mostly, although not exclusively, those with an advanced, fibrotic pulmonary disease. Its gold-standard diagnostic tool remains right heart catheterization (RHC). The decision to perform it relies on an expert decision after a non-invasive work-up, in which echocardiography remains the screening tool of choice. The mechanisms underlying SAPH, very often entangled, are crucial to define, as appropriate and personalized therapeutic strategies will aim at targeting the most significant ones. There are no recommendations so far as to the indications and modalities of the medical treatment of SAPH, which is based upon the opinion of a multidisciplinary team of sarcoidosis, pulmonary hypertension and sometimes lung transplant experts.

Phenotypes and Serum Biomarkers in Sarcoidosis.

Sarcoidosis is a multisystem disease, which is diagnosed on a compatible clinical presentation, non-necrotizing granulomatous inflammation in one or more tissue samples, and exclusion of alternative causes of granulomatous disease. Considering its heterogeneity, numerous aspects of the disease remain to be elucidated. In this context, the identification and integration of biomarkers may hold significance in clinical practice, aiding in appropriate selection of patients for targeted clinical trials. This work aims to discuss and analyze how validated biomarkers are currently integrated in disease category definitions. Future studies are mandatory to unravel the diverse contributions of genetics, socioeconomic status, environmental exposures, and other sociodemographic variables to disease severity and phenotypic presentation. Furthermore, the implementation of transcriptomics, multidisciplinary approaches, and consideration of patients' perspectives, reporting innovative insights, could be pivotal for a better understanding of disease pathogenesis and the optimization of clinical assistance.

Recurrence of sarcoidosis accompanied by lung cancer after drug-induced pulmonary sarcoidosis with lung injury.

Sarcoidosis is a multisystemic granulomatous disease that is frequently localized in the lungs and lymph nodes. We herein report a case of pulmonary sarcoidosis secondary to shin'iseihaito administration. During remission with 5 mg prednisolone/day of maintenance treatment, chest computed tomography revealed a mass in the left lower lobe with re-enlarged bilateral hilar/mediastinal lymph nodes. Transbronchial lung biopsy of the mass and endobronchial ultrasound-guided transbronchial needle aspiration of mediastinal lymph nodes revealed adenocarcinoma and noncaseating granulomas, respectively. Based on these findings, the patient was diagnosed with sarcoidosis recurrence associated with lung cancer without cancer metastasis. We present the case of sarcoidosis recurrence associated with lung cancer after drug-induced pulmonary sarcoidosis with lung injury. To our knowledge, this is the first report of sarcoidosis triggered by drug administration and lung cancer. Histological diagnosis of mediastinal lymphadenopathy with lung cancer is essential for differentiating metastasis from sarcoidosis.

Diagnostic delay of sarcoidosis: an integrated systematic review.

BACKGROUND: Sarcoidosis is a chronic inflammatory granulomatous disease of unknown cause. Delays in diagnosis can result in disease progression and poorer outcomes for patients. Our aim was to review the current literature to determine the overall diagnostic delay of sarcoidosis, factors associated with diagnostic delay, and the experiences of people with sarcoidosis of diagnostic delay. METHODS: Three databases (PubMed/Medline, Scopus, and ProQuest) and grey literature sources were searched. Random effects inverse variance meta-analysis was used to pool mean diagnostic delay in all types of sarcoidosis subgroup analysis. Diagnostic delay was defined as the time from reported onset of symptoms to diagnosis of sarcoidosis. RESULTS: We identified 374 titles, of which 29 studies were included in the review, with an overall sample of 1531 (694 females, 837 males). The overall mean diagnostic delay in all types of sarcoidosis was 7.93 months (95% CI 1.21 to 14.64 months). Meta-aggregation of factors related to diagnostic delay in the included studies identified three categories: (1) the complex and rare features of sarcoidosis, (2) healthcare factors and (3) patient-centred factors. Meta-aggregation of outcomes reported in case studies revealed that the three most frequent outcomes associated with diagnostic delay were: (1) incorrect diagnosis, (2) incorrect treatment and (3) development of complications/disease progression. There was no significant difference in diagnostic delay between countries with gatekeeper health systems (where consumers are referred from a primary care clinician to specialist care) and countries with non-gatekeeper systems. No qualitative studies examining people's experiences of diagnostic delay were identified. CONCLUSION: The mean diagnostic delay for sarcoidosis is almost 8 months, which has objective consequences for patient management. On the other hand, there is a paucity of evidence about the experience of diagnostic delay in sarcoidosis and factors related to this. Gaining an understanding of people's experiences while seeking a diagnosis of sarcoidosis is vital to gain insight into factors that may contribute to delays, and subsequently inform strategies, tools and training activities aimed at increasing clinician and public awareness about this rare condition. TRIAL REGISTRATION: PROSPERO Registration number: CRD42022307236.

Calcium Chaos in Sarcoidosis: A Tale of Severe Hypercalcemia's Diagnostic Challenge.

Sarcoidosis is a systemic inflammatory condition characterized by noncaseating granulomas. Lung involvement is typical, while extrapulmonary manifestations, notably lymphadenopathy, are observed in a significant proportion of cases. The etiology involves complex interactions among immune cells and mediators, resulting in granuloma formation capable of independently producing 1,25-dihydroxyvitamin D, leading to unregulated hypercalcemia and hypercalciuria. Diagnosis can be challenging, especially when hypercalcemia is the initial symptom. The presence of noncaseating granulomas on biopsy is characteristic of sarcoidosis. We present a case of severe hypercalcemia in a 53-year-old woman, initially suggestive of primary hyperparathyroidism due to non-suppressed intact parathyroid hormone (PTH) levels and unilateral intrathyroidal tracer uptake on a technetium 99m sestamibi parathyroid scan. The patient presented with hypertension, acute kidney injury, and severe hypercalcemia. Initial assessment, including a parathyroid scan, hinted at primary hyperparathyroidism. However, further evaluation, including chest computed tomography (CT) and endobronchial biopsy, revealed sarcoidosis with noncaseating granulomas. Prednisone therapy led to normalization of serum calcium and creatinine levels. The case underscores the complexities in diagnosing sarcoidosis, especially when presenting with severe hypercalcemia. Despite non-suppressed PTH and suggestive imaging, the final diagnosis relied on endobronchial biopsy findings. The study highlights the limitations of conventional diagnostic markers, emphasizing the need for a comprehensive and individualized approach.

Decreased serpin C1 in extracellular vesicles predicts response to methotrexate treatment in patients with pulmonary sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic granulomatous disease of unknown etiology primarily affecting the lungs. Treatment is needed when disease symptoms worsen and organ function deteriorates. In pulmonary sarcoidosis, prednisone and methotrexate (MTX) are the most common anti-inflammatory therapies. However, there is large inter-patient variability in response to treatment, and predictive response markers are currently lacking. OBJECTIVE: In this study, we investigated the predictive potential of biomarkers in extracellular vesicles (EVs) isolated from biobanked serum of patients with pulmonary sarcoidosis stored prior to start of therapy. METHODS: Protein concentrations of a four-protein test panel of inflammatory proteins were measured in a discovery (n = 16) and replication (n = 129) cohort of patients with sarcoidosis and 47 healthy controls. Response to therapy was defined as an improvement of the absolute score of > 5% forced vital capacity (FVC) and/or > 10% diffusion lung of carbon monoxide (DLCO) after 24 weeks compared to baseline (before treatment). RESULTS: Serum protein levels differed between EV fractions and serum, and between sarcoidosis cases and controls. Serpin C1 concentrations in the low density lipid particle EV fraction were lower at baseline in the group of patients with a good response to MTX treatment in both the discovery cohort (p = 0.059) and in the replication cohort (p = 0.032). EV Serpin C1 showed to be a significant predictor for response to treatment with MTX (OR 0.4; p = 0.032). CONCLUSION: This study shows that proteins isolated from EVs harbor a distinct signal and have potential as new predictive therapy response biomarkers in sarcoidosis.

Clinical Pharmacology in Sarcoidosis: How to Use and Monitor Sarcoidosis Medications.

When sarcoidosis needs treatment, pharmacotherapy is usually required. Although glucocorticoids work reliably and relatively quickly for sarcoidosis, these drugs are associated with numerous significant side effects. Such side effects are common in sarcoidosis patients, as the disease frequently has a chronic course and glucocorticoid treatment courses are often prolonged. For these reasons, corticosteroid-sparing and corticosteroid-replacing therapies are often required for sarcoidosis. Unfortunately, many healthcare providers who care for sarcoidosis patients are not familiar with the use of these agents. In this manuscript, we provide a review of the pharmacotherapy of sarcoidosis. We discuss the mechanism of action, dosing, side-effect profile, approach to monitoring and patient counselling concerning glucocorticoids, and the common alternative drugs recommended for use in the recent European Respiratory Society (Lausanne, Switzerland) Sarcoidosis Treatment Guidelines. We also discuss the use of these agents in special situations including hepatic insufficiency, renal insufficiency, pregnancy, breastfeeding, vaccination, and drug-drug interactions. It is hoped that this manuscript will provide valuable practical guidance to clinicians who care for sarcoidosis patients.

Sarcoidosis in first- and second-generation immigrants: a cohort study of all adults 18 years of age and older in Sweden.

BACKGROUND: There is a lack of studies on sarcoidosis among immigrants, which is of interest as there may be genetic and environmental characteristics affecting immigrants from certain countries. We aimed to study hazard ratios (HRs) of sarcoidosis in first- and second-generation immigrants, comparing them with native Swedes in the total adult Swedish population. METHODS: We conducted a nationwide study of individuals ≥18 y of age. Sarcoidosis was defined as at least two registered diagnoses in the National Patient Register between 1 January 1998 and 31 December 2018. Cox regression analysis was used to estimate HRs with 99% confidence intervals (CIs) of first registration of sarcoidosis in first- and second-generation immigrants compared with native Swedes. The Cox regression models were stratified by sex and adjusted for age, comorbidities and sociodemographic characteristics. RESULTS: In total, 6 175 251 were included in the first-generation study, with 12 617 cases of sarcoidosis, and 4 585 529 in the second-generation study, with 12 126 cases. The overall sarcoidosis risk was lower in foreign-born men (fully adjusted HR 0.63 [99% CI 0.57 to 0.69]) but not in foreign-born women (fully adjusted HR 0.98 [99% CI 0.90 to 1.06]). The overall risk was slightly lower in second-generation immigrants (HR 0.82 [99% CI 0.78 to 0.88]). Women from Asia exhibited a higher risk (HR 1.25 [99% CI 1.02 to 1.53)], while a potential trend was observed among women from Africa (HR 1.47 [99% CI 0.99 to 2.19]). CONCLUSIONS: Sarcoidosis risk was lower in foreign-born men but not in women and also lower in second-generation immigrants.

Sarcoidosis presenting as multiple osseous lesions.

Sarcoidosis is a multisystem inflammatory condition presenting with the formation of noncaseating granulomas. These granulomas can be found in nearly every organ of the body, but in 90% of cases the lungs are involved. Osseous manifestations are seen in only 3% to 13% of cases and are typically seen alongside the more common pulmonary manifestations. These lesions can be misdiagnosed as metastatic cancer so biopsy, along with clinical correlation and exclusion of other diseases, is necessary to make the diagnosis. Most patients with primary osseous sarcoidosis remain asymptomatic but routine monitoring is necessary to identify progression to lesion growth, cardiac manifestations, and respiratory involvement.

Deep lymph node enlargement and renal failure caused by hypercalcemia­associated sarcoidosis: A case report.

Sarcoidosis is a rare disease that severely affects the lungs and superficial lymph nodes. In addition, this disease can also affect the skin, eyes and kidneys to varying degrees. The present report described a 32-year-old male patient who was admitted to Renmin Hospital of Wuhan University (Wuhan, China) due to joint pain in the extremities. He was diagnosed with uncorrectable hypercalcemia. A lymph node biopsy revealed the hypercalcemia to be associated with sarcoidosis, with the patient also demonstrating renal failure and lymph node enlargement. Administration of glucocorticoids provided benefits in terms of both primary and recurrent sarcoidosis, which also improved and preserved renal function. After being prescribed with oral prednisone treatment, blood calcium levels returned to normal, which indicated markedly improving renal function. However, the discontinuation of glucocorticoids for 2 months resulted in increased serum calcium and creatinine levels, both of which returned to abnormal levels. Overall, the present case report suggests that clinicians should actively perform sarcoidosis treatment in clinical practice to overcome any unexpected results associated with organ damage.

Vasoproliferative Tumor Secondary to Sarcoidosis-Associated Intermediate Uveitis.

We report the visual and clinical outcomes of a middle-aged woman who presented with exudative retinal detachment (ERD) secondary to a vasoproliferative tumor (VPT) in an eye with sarcoidosis-associated intermediate uveitis. A 55-year-old woman previously diagnosed with sarcoidosis presented with decreased vision in the left eye (LE). Visual acuity in the LE was counting fingers. She had active vitritis, and a peripheral retinal vascular mass was noted in the superotemporal periphery. The mass was associated with ERD involving the posterior pole. The patient was managed with systemic and intravitreal steroids, and cyclosporine was subsequently added as a steroid-sparing agent. Because of recurrence of ERD, the patient underwent pars plana vitrectomy, and cryotherapy and laser photocoagulation were applied to the VPT. Two months postoperatively, visual acuity in the LE improved to 6/10. There was marked regression of the VPT and total resolution of the ERD. In conclusion, we report a favorable visual and clinical outcome in a patient with VPT-associated ERD who responded to a combination of medical therapy and surgical intervention. VPT may lead to different remote complications, so timely diagnosis of these tumors and proper management of their complications is warranted.