Treatment Of Sarcoidosis Research Articles

Five principles and protocols for the clinician based on the 2021 ERS and BTS statements for treating sarcoidosis.

The European Respiratory Society (ERS) and the British Thoracic Society (BTS) have recently published their statements on the treatment of sarcoidosis. There are five key questions in sarcoidosis treatment that need to be addressed: when to treat, how to initiate treatment, how long to treat, when and how to change treatment, and how to treat relapses. Herein, we describe the principles and protocols to answer these questions based on the ERS and BTS statements and other expert reviews. Pulmonary or extrapulmonary sarcoidosis should be treated with anti-inflammatory therapy if it significantly impairs the quality of life (QoL), causes significant organ dysfunction, or threatens to cause organ damage, disability, or death. If treatment is initiated for improving the QoL alone, low-dose (10 mg/day) prednisone is a good initial treatment that can be tapered and stopped over 3 months. Disease that causes significant organ dysfunction needs to be treated with medium-dose glucocorticoids (initial daily dose, 20 mg of prednisone equivalent) tapered over a minimum duration of 6 months. Worsening of disease while tapering treatment indicates that longer (9-24 months) treatment may be necessary. If a daily prednisone dose of >10 mg is required for >6 months to maintain remission, it is best to use a second-line drug such as methotrexate or azathioprine. Anti-tumor necrosis factor agents, such as infliximab or adalimumab, may be used to treat inflammatory disease that persists on combination treatment with glucocorticoids and a second-line agent.

Sarcoidosis Treatment Patterns in the United States: 2016-2022

There are limited FDA-approved medications and real-world data on sarcoidosis treatment in the U.S. and concordance of practice patterns with guideline recommendations have not been well characterized. What are the practice patterns and factors associated with treatment for patients with sarcoidosis in the year following diagnosis? We conducted a retrospective analysis of patients with sarcoidosis from 2016 - 2022 using a multicenter, all-payer, claims database (TriNetX). We ascertained treatments with corticosteroids and/or non-steroidal immunosuppressive medications (methotrexate, mycophenolate, leflunomide, hydroxychloroquine, cyclophosphamide, infliximab, adalimumab, azathioprine, rituximab, and janus kinase inhibitors) within one year of diagnosis. We summarized treatment rates, sequence of prescribed medications by mean rank, and used multivariable logistic regression analyses to identify factors associated with treatment. Out of 13,330 patients with sarcoidosis meeting inclusion, 5,671 (42.5%) received treatment within a year of diagnosis. Of those treated, 60% received steroids alone, 13% received non-steroidal immunosuppressives alone, and 27% received both. Further, 25% of treated patients received a non-steroidal immunosuppressive as their first medication. Corticosteroids had the lowest mean rank order, indicating they were, on average, the first medication initiated. Among those with pulmonary or cutaneous involvement, the second medication initiated on average was hydroxychloroquine, while in those with cardiac or neurologic involvement it was adalimumab and mycophenolate, respectively. Factors associated with higher odds of treatment were Black race, organ involvement at baseline (pulmonary, cardiac, and neurologic), and comorbid diagnoses (fatigue, hypercalcemia, and ILD). Within the first year of diagnosis, 43% of patients with sarcoidosis were started on treatment. Non-steroidal immunosuppressives were used in 40% of treated patients. While factors associated with treatment initiation aligned with guideline recommendations, practice patterns of treatment were variable, particularly in choice and sequence of non-steroidal immunosuppressive therapy, underscoring the need for future trials and comparative effectiveness studies.

Evaluating corticosteroid treatment strategies for cardiac sarcoidosis: analysis of the nationwide claims-based JROAD-DPC dataset

Abstract Background Corticosteroid-based immunosuppressive therapy is the cornerstone of treatment for cardiac sarcoidosis (CS), aimed at preventing severe adverse events including death, heart failure and lethal arrhythmic events. Nevertheless, data on the optimal initial dosing, appropriate tapering schedules, suitable maintenance dosages, and the recurrence rates among patients are insufficient. Purpose This study sought to scrutinize real-world data on corticosteroid therapy regimen for CS and to reassess optimal treatment protocols. Methods From the Japanese Diagnosis Procedure Combination database, 6,282 patients with hospitalized CS were identified between 2012 and 2022. Among them, 3,067 CS patients who were initiated on corticosteroid therapy during hospitalization were analyzed. We examined the baseline patient characteristics and treatment strategies for corticosteroid therapy, including starting dose, tapering period, maintenance dose, and their correlation with the onset of adverse events. Results The cohort had a mean age was 63±11 years, and 1,256 patients (41.0 %) were female. The starting dose of corticosteroids was 30.3±6.9 mg, with 88.6% of patients receiving a dose of ≧30 mg/day. The doses of corticosteroids at 30, 60, 90, 120, 150 and 180 days post-discharge were 21.4±9.8, 15.7±6.9, 12.2±5.7, 10.4±5.0, 9.3±4.5 and 9.0±4.6 mg, respectively. By day 180, 83.7% of the patients were maintained on ≦10 mg/day. However, 17.1 % of patients required an increase in corticosteroid dosage during the tapering course, primarily due to exacerbation of sarcoidosis. When analyzing only the group without corticosteroid escalation up to 180 days post-discharge, the average corticosteroid dose was 8.7±3.8 mg, with 95.3% of patients on ≦10 mg/day. We observed 965 re-hospitalization (31.5 %) during follow-up, with 58.8% of these patients having corticosteroid escalation to ≧30 mg, and 12.8% of patients received second-line immunosuppressive therapy, such as methotrexate. Conclusion The majority of CS patients were initiated on a corticosteroid regimen of 30 mg/day, which was subsequently tapered to below 10 mg/day by day 180. However, non-negligible number of patients experienced clinical events or relapse, underscoring the necessity for vigilant follow-up during corticosteroid therapy.Figure

The Management of Patients with Extrapulmonary Sarcoidosis in Rheumatology Clinic

Abstract Background This study aimed to evaluate patients with extrapulmonary and refractory sarcoidosis who were followed up on in our rheumatology clinic for a long follow-up period and to summarise the applications in rheumatology practice. Materials and Methods The study included patients diagnosed with sarcoidosis at our institution between 2010 and 2022. Patientsʼ age, sarcoidosis diagnosis dates, inflammatory rheumatic disease (iRMD) diagnoses, autoimmune markers, and imaging findings were all evaluated. Estimates were made for cases of glucocorticoid (GC) use and cumulative and mean daily GC exposures. Results 90 patients with sarcoidosis, 79 (87.8) female and 11 (12.2) male, whose mean age was 56.4±12.4 years, were included. Since 48 (53.3%) of the patients required at least one additional treatment in addition to CS, they were classified as having refractory sarcoidosis and followed up accordingly. While 43 (89%) of the patients received second-line sarcoidosis treatment, it was found that 5 patients were switched to third-line sarcoidosis treatment (p<0.001). Comorbidity distributions of refractory and nonrefractory patients were similar. It was determined that 9 (10%) patients had a history of osteoporotic fracture. Conclusions In conclusion, it appears critical to develop a detailed patient management plan and a multidisciplinary approach in the early stages of extrapulmonary sarcoidosis management. There is currently no detailed algorithm covering refractory disease definition and treatment practice differences.

Adalimumab for the Treatment of CNS Sarcoidosis

Adalimumab for the Treatment of CNS Sarcoidosis

Position paper of the Austrian Society for Rheumatology and the Austrian Society for Pneumology on the diagnosis and treatment of sarcoidosis 2024

In many cases sarcoidosis is a multisystemic disease that requires interdisciplinary medical cooperation in the diagnostics, treatment and medical care during follow-up. Due to the often chronic course, it is of utmost importance to include patients with their priorities and wishes at an early stage and extensively in disease management and to establish a shared decision making whenever possible. In the process of writing this joint position paper, the expert group on interstitial and orphan lung diseases of the Austrian Society for Pulmonology and the working group on rheumatological lung disorders of the Austrian Society for Rheumatology and Rehabilitation sought to include patient advocacy groups as well as experts for rare organ manifestations of sarcoidosis. This position paper is not only meant to reflect current scientific and clinical standards but should also focus the national expertise and by networking and exchange to be a first step to strengthen cooperation between stakeholders to ultimately improve care for patients with sarcoidosis.

Inhaled budesonide and pulmonary sarcoidosis revisited.

Results of a few controlled clinical studies have been reported with inhaled corticosteroids (ICS) in patients with pulmonary sarcoidosis. Some evidence of efficacy has been observed, but mainly with the ICS budesonide (BUD). These clinically important and statistically significant results are restricted to maintenance therapy with BUD after induction of treatment with systemic corticosteroids for a few weeks or months. Positive results have also been described in patients with relapses after earlier treatment with oral corticosteroids. A possible explanation for BUD's efficacy in patients with parenchymal lesions could be that inhaled BUD is rapidly absorbed into systemic circulation, creating plasma peaks which result in systemic anti-inflammatory activity in both peripheral airways and lung tissue. At airway level this steroid activity is furthermore prolonged because a BUD fraction is intracellularly, reversibly transformed into lipophilic BUD-oleate. These mechanisms have been proposed to explain the theoretically unexpected similar efficacy of BUD compared with more lipophilic ICSs in patients with asthma and COPD. In this review we summarize the results of clinical studies with ICSs in patients with pulmonary sarcoidosis. It is obvious that current ICSs, including BUD, cannot generally be recommended as such for treatment of sarcoidosis. However, using BUD as a model substance further pharmacologic and kinetic studies could possibly define a kinetic profile giving optimal partitioning between airway and systemic activity with less adverse systemic risks. Such a substance could replace or reduce oral corticosteroids in the treatment of airway and pulmonary parenchymal diseases.

Effects of Azithromycin on Blood Inflammatory Gene Expression and Cytokine Production in Sarcoidosis

IntroductionIn sarcoidosis granulomas, monocyte-derived macrophages are activated by pro-inflammatory cytokines including TNF and IL-6. Current drug treatment for sarcoidosis aims to suppress inflammation but disabling side effects can ensue. The macrolide azithromycin may be anti-inflammatory. We aimed to determine whether treatment with azithromycin affects blood inflammatory gene expression and monocyte functions in sarcoidosis.MethodsBlood samples were collected from patients with chronic pulmonary sarcoidosis enrolled in a single arm, open label clinical trial who received oral azithromycin 250 mg once daily for 3 months. Whole blood inflammatory gene expression with or without LPS stimulation was measured using a 770-mRNA panel. Phenotypic analysis and cytokine production were conducted by flow cytometry and ELISA after 24h stimulation with growth factors and TLR ligands. mTOR activity was assessed by measuring phosphorylated S6RP.ResultsDifferential gene expression analysis indicated a state of heightened myeloid cell activation in sarcoidosis. Compared with controls, sarcoidosis patients showed increased LPS responses for several cytokines and chemokines. Treatment with azithromycin had minimal effect on blood gene expression overall, but supervised clustering analysis identified several chemokine genes that were upregulated. At the protein level, azithromycin treatment increased LPS-stimulated TNF and unstimulated IL-8 production. No other cytokines showed significant changes following azithromycin. Blood neutrophil counts fell during azithromycin treatment whereas mononuclear cells remained stable. Azithromycin had no detectable effects on mTOR activity or activation markers.ConclusionBlood myeloid cells are activated in sarcoidosis, but azithromycin therapy did not suppress inflammatory gene expression or cytokine production in blood.Trial registration: EudraCT 2019-000580-24 (17 May 2019)

Clinical trials in pulmonary sarcoidosis; what is needed, what is happening and what is next?

There is a clinical unmet need to improve treatment for patients with pulmonary sarcoidosis. Both retrospective and prospective drug trials are hampered by the fact that patients with sarcoidosis are characterized by a heterogeneous presentation and disease course. In this review, an overview is given of different drug trials in pulmonary sarcoidosis with an emphasis on different primary endpoints and the problems related to them. In recent years, using significant input from patients with sarcoidosis, different task-forces/studies tried to develop a core set of most important outcomes to measure in future studies on treatment of sarcoidosis. Furthermore, at present, three major clinical trials are being conducted on new drugs for treatment of pulmonary sarcoidosis. Progress has been made to develop a core set of outcomes measures that can be used in making a combined primary endpoint in future drug trials in sarcoidosis.

Can FDG-PET Imaging Identify Cardiac Sarcoidosis Disease Phenotypes?

Despite the scarcity of data, most guidelines have advocated for the treatment of cardiac sarcoidosis with corticosteroids. However, there is heterogeneity in disease presentation and response to treatment, which can make treatment challenging. The ability to identify disease phenotypes to allow for tailored therapy is therefore highly desirable. This review will seek to outline the disease phenotypes of cardiac sarcoidosis and the role that FDG-PET imaging can play in identifying these phenotypes to optimize disease diagnosis and treatment management. FDG PET can identify cardiac sarcoidosis and is being increasingly used to monitor therapeutic response to immunosuppressive therapy, to follow treatment response after discontinuation of corticosteroid therapy, and to evaluate for disease relapse. Modern quantitative techniques using FDG PET imaging may allow for even better phenotypic disease characterization and the ability to track the response to immunosuppression more accurately. FDG PET currently plays an important role in cardiac sarcoidosis diagnosis. However, it also affords us the opportunity to offer insights into cardiac sarcoidosis disease phenotypes to better understand the underlying disease process and in the future may allows us to tailor therapies accordingly.

САРКОИДОЗ, ТРУДНОСТИ ДИАГНОСТИКИ

The incidence of sarcoidosis in Russia has not been studied enough. The clinical signs of sarcoidosis are diverse, and the lack of specific diagnostic tests makes noninvasive diagnosis difficult. In general therapeutic practice, in the case of an atypical course of the disease, diagnosis is complicated by the need for a differential diagnosis with many syndrome-like diseases. The etiology of sarcoidosis is still unknown. According to recent concepts, the cause of its occurrence cannot be considered a single factor, it is a combination of genetic, environmental, infectious and immunological causes. In this article, the author examines the main difficulties faced by doctors in the diagnosis of sarcoidosis. The clinical manifestations of the disease are analyzed, as well as methods of its detection, such as bronchoscopy, biopsy and laboratory tests. Possible diagnostic errors and how to avoid them are also considered. Understanding these difficulties will help improve the diagnosis and treatment of sarcoidosis, leading to more effective disease management.

Features of the current course and treatment of pulmonary sarcoidosis (case from clinical practice)

Features of the current course and treatment of pulmonary sarcoidosis (case from clinical practice)

The clinical management of hepatic sarcoidosis: A systematic review.

Hepatic sarcoidosis is an uncommon clinical condition in which clear recommendations are lacking in its treatment. We aimed to review systematically the literature on hepatic sarcoidosis treatment to guide clinicians. Using MEDLINE, PubMed, CINAHL, Cochrane Library, and Google Scholar databases, we searched original articles on clinical studies reporting the outcome of adult hepatic sarcoidosis patients following treatment with various pharmacological agents. The primary end point was focused on assessing symptomatic relief and biochemical improvement posttreatment. Out of 614 retrieved references, 34 published studies were eligible, providing data for a total of 268 patients with hepatic sarcoidosis. First-line therapy with corticosteroids alone was reported in 187 patients, whilst ursodeoxycholic acid (UDCA) was used in 40 patients. Symptomatic and biochemical responses were reported among 113(60.4%) and 80(42.8%) cases of corticosteroids respectively, whereas UDCA showed a complete response in 23(57.5%) patients. Second-line therapy was used in steroid-refractory cases, with most cases being reported for azathioprine (n = 32) and methotrexate (n = 28). Notably, 15(46.9%) and 11(39.2%) patients showed both clinical and biochemical responses respectively. Biological therapy including anti-tumor necrosis factor (anti-TNF) was used as third line therapy in twelve cases with a 72.7% symptomatic and biochemical response rate each. The quality of evidence for the treatment of hepatic sarcoidosis was poor. Nevertheless, it appears that corticosteroid or UDCA may be utilized as first-line therapy. For cases that are refractory to corticosteroids, steroid-sparing immunosuppressive agents and anti-TNF have shown some promising results, but further high-quality studies are required.

Efficacy and safety of Infliximab in systemic sarcoidosis according to GenPhenReSa organ-involvement phenotype: a retrospective study of 55 patients

BackgroundInfliximab is currently recommended as a third-line treatment for refractory sarcoidosis. Data in function of clinical phenotype are currently lacking. We evaluated patients’ characteristics and responses to infliximab according to their GenPhenReSa cluster.MethodsWe evaluated clinical and biological characteristics of patients diagnosed with sarcoidosis who received infliximab between September 2008 and April 2019 at our centre.ResultsFifty-five patients (median disease duration, 87 months) received infliximab: 48 (87%) as a second- or third-line treatment, and 7 (13%) as a first-line treatment. After a median duration of 12 months, 24 (45%) and 14 (25%) patients achieved complete and partial responses, respectively, together with a significant decrease in the number of affected organs and tapering of steroid doses. All patients with neurosarcoidosis (OR 17), 90% in group 2 (ocular-cardiac-cutaneous-CNS, OR 7.4), and approximately two-thirds of those in groups 1 (abdominal organs), 4 (pulmonary-lympho-nodal), and 5 (extrapulmonary), achieved a response, whereas patients in group 3 (musculoskeletal-cutaneous) had a treatment-failure OR of 9. Infliximab could be stopped after complete remission was achieved in 7 patients: 4 relapsed after a median of 6 months. Overall, 36% of patients experienced serious adverse events, mainly infections, which led to treatment cessation in 29% of patients and caused two deaths.ConclusionsOther than patients with musculoskeletal-cutaneous involvement (group 3), infliximab led to a good response for patients with CNS (group 2) and liver (group 1) organ-predominant sarcoidosis. However, it led to serious infections and merely suspended sarcoidosis, so further research on factors predictive of relapse is needed.

Kidney manifestations of sarcoidosis

Renal involvement is a clinically relevant organ manifestation of sarcoidosis, leading to increased morbidity and complications. Although the exact incidence remains unknown, renal disease is likely to occur in up to one third of all sarcoidosis patients. Every patient with newly diagnosed sarcoidosis should receive a renal work-up and screening for disrupted calcium metabolism.Amid various forms of glomerulonephritis, granulomatous interstitial nephritis is the most common one, but it rarely leads to renal impairment. Histologically, granulomas can be absent. Nephrocalcinosis and nephrolithiasis are frequent forms when hypercalcaemia or hypercalciuria occur. Drugs used for treatment of systemic sarcoidosis can also cause renal damage.Due to its high heterogeneity, renal sarcoidosis can be difficult to treat. Glucocorticoids and various immunosuppressive treatments have been proven to be effective based on case series, but clinical trials are lacking. A treatment guideline for renal sarcoidosis is urgently needed.In this review article, we present an overview of the different forms of renal sarcoidosis and the diagnostic steps to confirm renal involvement; in addition, we provide insights on the management and available treatments. A better understanding regarding the pathogenesis of sarcoidosis is the key for the development of more specific, targeted therapies.

Sarcoidosis of the Skin as an Interdisciplinary Problem

Sarcoidosis is a disease of unknown etiology characterized by the formation of epithelioid cell granulomas in several organs or tissues without caseous necrosis (fibrinoid necrosis may occur). With sarcoidosis, almost all organs and tissues can be affected, which determines the interdisciplinary nature of the problem. Skin sarcoidosis is one of the most common manifestations of systemic sarcoidosis. At the same time, the role of dermatologists in the diagnosis of sarcoidosis is exceptionally large, since skin lesions are often the key to the discovery of systemic sarcoidosis, which allows internists to purposefully and timely diagnose and treat lesions of internal organs. Skin rashes in patients with sarcoidosis may occur secondarily against the background of specific lesions of the lungs, intrathoracic nodes and other internal organs, however, skin sarcoidosis may also develop primarily. All forms of skin sarcoidosis may be the only manifestation of the disease, and it is impossible to distinguish clinically and histologically between skin changes in systemic sarcoidosis and skin lesions alone. Treatment of skin sarcoidosis often presents great difficulties and includes, depending on the prevalence and activity of the process, local (corticosteroids, tacrolimus) and systemic therapy (immunomodulators, immunosuppressors, TNF inhibitors).

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 and Polymethyl Methacrylate (PMMA) Granulomas following COVID-19 Vaccination (ChAdOx1): Successful Treatment with Tofacitinib.

Sarcoidosis and complications related to fillers have been reported following the COVID-19 vaccination. Additionally, cutaneous sarcoidosis has been observed around polymethyl methacrylate (PMMA) injection sites. Foreign-body reactions to PMMA can occur simultaneously with systemic sarcoidosis, suggesting a shared pathogenic mechanism between both conditions. To report a case of sarcoidosis and PMMA granulomas following COVID-19 vaccination (ChAdOx11), successfully treated with tofacitinib. We present a 59-year-old woman who developed systemic sarcoidosis and a granulomatous reaction to PMMA filler following the COVID-19 vaccination (ChAdOx11). Notably, both PMMA and the vaccine were potential triggers for sarcoidosis. Treatment with tofacitinib produced marked improvement in both the cutaneous and pulmonary involvement of sarcoidosis and the granulomatous reaction to PMMA. This successful outcome suggests tofacitinib, a pan-JAK inhibitor, an alternative treatment for cutaneous and systemic sarcoidosis, as well as a potential therapy for granulomatous complications of dermal fillers, such as PMMA.

Efficacy and safety of mTOR inhibition in cutaneous sarcoidosis: a single-centre trial

Sarcoidosis is an inflammatory condition that can affect various organs and tissues, causing the formation of granulomas and subsequent functional impairment. The origin of sarcoidosis remains unknown and there are few treatment options. Mechanistic target of rapamycin (mTOR) activation is commonly seen in granulomas of patients across different tissues and has been shown to induce sarcoidosis-like granulomas in a mouse model. This study aimed to examine the efficacy and safety of the mTOR inhibitor sirolimus as a treatment for cutaneous sarcoidosis. We did a single-centre, randomised study treating patients with persistent and glucocorticoid-refractory cutaneous sarcoidosis with sirolimus at the Vienna General Hospital, Medical University of Vienna (Vienna, Austria). We recruited participants who had persistent, active, and histologically proven cutaneous sarcoidosis. We used an n-of-1 crossover design in a placebo-controlled, double-blind topical treatment period and a subsequent single-arm systemic treatment phase for 4 months in the same participants. Participants initially received either 0·1% topical sirolimus in Vaseline or placebo (Vaseline alone), twice daily. After a washout period, all participants were subsequently administered a 6 mg loading dose followed by 2 mg sirolimus solution orally once daily, aiming to achieve serum concentrations of 6 ng/mL. The primary endpoint was change in the Cutaneous Sarcoidosis Activity and Morphology Index (CSAMI) after topical or systemic treatment. All participants were included in the safety analyses, and patients having completed the respective treatment period (topical treatment or systemic treatment) were included in the primary analyses. Adverse events were assessed at each study visit by clinicians and were categorised according to their correlation with the study drug, severity, seriousness, and expectedness. This study is registered with EudraCT (2017-004930-27) and is now closed. 16 participants with persistent cutaneous sarcoidosis were enrolled in the study between Sept 3, 2019, and June 15, 2021. Six (37%) of 16 participants were men, ten (63%) were women, and 15 (94%) were White. The median age of participants was 54 years (IQR 48-58). 14 participants were randomly assigned in the topical phase and 2 entered the systemic treatment phase directly. Daily topical treatment did not improve cutaneous lesions (effect estimate -1·213 [95% CI -2·505 to 0·079], p=0·066). Systemic treatment targeting trough serum concentrations of 6 ng/mL resulted in clinical and histological improvement of skin lesions in seven (70%) of ten participants (median -7·0 [95% CI -16·5 to -3·0], p=0·018). Various morphologies of cutaneous sarcoidosis, including papular, nodular, plaque, scar, and tattoo-associated sarcoidosis, responded to systemic sirolimus therapy with a long-lasting effect for more than 1 year after treatment had been stopped. There were no serious adverse events and no deaths. Short-term treatment with systemic sirolimus might be an effective and safe treatment option for patients with persistent glucocorticoid-refractory sarcoidosis with a long-lasting disease-modulating effect. The effect of sirolimus in granulomatous inflammation should be investigated further in large, multi-centre, randomised clinical trials. Vienna Science and Technology Fund, Austrian Science Fund.

Hospitalizations of patients with sarcoidosis before and during the COVID-19 pandemic in Poland.

Sarcoidosis is a multisystemic granulomatous disease that mostly affects the lungs and lymphatic system. Due to its rarity and variable clinical course, analyses of factors related to sarcoidosis should be based on large databases and long observation periods. The aim of this study was to determine the characteristics of patients with sarcoidosis hospitalized in Poland over a long period (2016-2021). We conducted a retrospective study using hospital discharge records compiled by the National Institute of Public Health NIH - National Research Institute. We analyzed the records of patients with sarcoidosis from the entire Polish population at their first hospitalization. We identified a total of 15 548 first-time hospitalizations for sarcoidosis. The mean annual disease incidence was 6.8 cases per 100 000. The mean (SD) age of the patients was 45.8 (13.6) years, and it was lower in men than in women (42.9 [12.5] vs 49.8 [14.2] years; P <0.001). There were significantly more hospitalizations among city dwellers (62.3% vs 37.3% for rural residents; P <0.001). At the beginning of the COVID‑19 pandemic in Poland there was a decrease in the number of hospitalizations for sarcoidosis, followed by an increase in the subsequent year. The all‑cause in‑hospital death rate was significantly higher during the COVID‑19 pandemic, as compared with the period before the pandemic (7.2 vs 2.3 per 1000; P <0.001). Health care changes related to the outbreak of the COVID‑19 pandemic may have increased the health debt for inpatient sarcoidosis treatment. The occurrence of sarcoidosis in Poland may be related to demographic and territorial factors.