Fibrotic Pulmonary Sarcoidosis.

Fibrotic pulmonary sarcoidosis (fPS) affects about 20% of patients. fPS carries a significant morbidity and mortality. However, its prognosis is highly variable, depending mainly on fibrosis extent, functional impairment severity, and the development of pulmonary hypertension. Moreover, fPS outcomes are also influenced by several other complications, including acute exacerbations, and infections. fPS natural history is unknown, in particular regarding the risk of progressive self-sustaining fibrosis. The management of fPS is challenging, including anti-inflammatory treatment if granulomatous activity persists, rehabilitation, and in highly selected patients antifibrotic treatment and lung transplantation.

Living with sarcoidosis: Virtual roundtable dialogue with patients and healthcare professionals.

BACKGROUND: Sarcoidosis is a multisystem disease, characterised by the infiltration of various organs by non-necrotising granulomas. The disease's heterogeneity complicates the study of patients' experiences. OBJECTIVE: To gather insight into life experiences, unmet needs and views on hypothetically emerging treatment options among patients living with sarcoidosis. METHODS: Multinational, virtual, interactive, moderated discussion of specific questions between people with sarcoidosis, with experienced clinicians participating. RESULTS: Nine patients with sarcoidosis from Australia, Denmark, Germany, Italy, Japan and the US, and three clinicians took part. All patients had pulmonary sarcoidosis, self-assessed as mild by five patients. The path to diagnosis was convoluted, with up to four physicians and a large number of tests involved. There was agreement that the process would be improved by earlier referral to specialists. The patients made a clear distinction between 'living with a condition' (adapting to the disease) and 'being ill'. The concept of remission was viewed sceptically as disease might develop in multiple organs. Panellists had a pragmatic attitude to therapies: side effects during a treatment course were accepted if overall symptoms improved. When considering hypothetical new therapies, improved quality of life (QoL) was the most important need; improved tolerability had lower priority. New therapies should be targeted on reducing disease progression and improving symptoms and QoL rather than corticosteroid withdrawal. CONCLUSIONS: The interactive exchange provided insights into the need for earlier specialist referrals, distrust of the concept of remission in sarcoidosis, and the need for therapies targeted on reducing disease progression and improving symptoms and QoL.

WASOG statement on the diagnosis and management of sarcoidosis-associated pulmonary hypertension.

Sarcoidosis-associated pulmonary hypertension (SAPH) is an important complication of advanced sarcoidosis. Over the past few years, there have been several studies dealing with screening, diagnosis and treatment of SAPH. This includes the results of two large SAPH-specific registries. A task force was established by the World Association of Sarcoidosis and Other Granulomatous disease (WASOG) to summarise the current level of knowledge in the area and provide guidance for the management of patients. A group of sarcoidosis and pulmonary hypertension experts participated in this task force. The committee developed a consensus regarding initial screening including who should undergo more specific testing with echocardiogram. Based on the results, the committee agreed upon who should undergo right-heart catheterisation and how to interpret the results. The committee felt there was no specific phenotype of a SAPH patient in whom pulmonary hypertension-specific therapy could be definitively recommended. They recommended that treatment decisions be made jointly with a sarcoidosis and pulmonary hypertension expert. The committee recognised that there were significant defects in the current knowledge regarding SAPH, but felt the statement would be useful in directing future studies.

[Pulmonary and Cardiac Sarcoidosis - Diagnosis and Therapy]. / Diagnostik und Therapie der pulmonalen und kardialen Sarkoidose.

Sarcoidosis occurs predominantly in younger adults and may involve multiple organ systems. Although classical features such as bihilar lymphadenopathy, low grade fever, fatigue, pulmonary opacities, ocular lesions and arthritis occur frequently it must be kept in mind that sarcoidosis is able to mimic virtually any other disease. A thorough and systematic diagnostic strategy is warranted since even the histological hallmark of non-caseating granulomas occurs in a variety of other granulomatous diseases and even malignancies. A firm diagnosis is based on a match of clinical features, imaging results and histopathological findings. The Scadding classification describes four different types, not stages, of thoracic sarcoidosis based on mediastinal lymph node and lung parenchyma involvement. Medical treatment of pulmonary sarcoidosis is indicated only in patients exhibiting progressive disease and/or organ function impairment. Cardiac sarcoidosis manifests itself by clinical signs of heart failure, impaired cardiac function and arrhythmias including ventricular tachycardia, ventricular fibrillation and AV-conduction abnormalities. Patients with symptomatic or suspected cardiac sarcoidosis require rapid and elaborate diagnostic testing including cardiac MRI and PET imaging. Referral to a specialized center should be considered to establish a firm diagnosis and to initiate medical treatment and eventual device implantation. Oral corticosteroids, as the initial medical treatment of choice, carry side effects that must be weighed carefully against clinical benefits. Immunosuppressive therapy with methotrexate, azathioprine or TNF-blockers is usually reserved for patients that are either not responsive or intolerant to systemic steroids or that require steroid maintenance therapy above the cushing threshold. Diagnosed early and treated correctly, pulmonary and cardiac sarcoidosis mostly carry a favorable prognosis.

Doxycycline treatment of high-risk COVID-19-positive patients with comorbid pulmonary disease.

Infection with novel SARS-CoV-2 carries significant morbidity and mortality in patients with pulmonary compromise, such as lung cancer, autoimmune disease, and pneumonia. For early stages of mild to moderate disease, care is entirely supportive.Antiviral drugs such as remdesivir may be of some benefit but are reserved for severe cases given limited availability and potential toxicity. Repurposing of safer, established medications that may have antiviral activity is a possible approach for treatment of earlier-stage disease. Tetracycline and its derivatives (e.g. doxycycline and minocycline) are nontraditional antibiotics with a well-established safety profile, potential efficacy against viral pathogens such as dengue fever and chikungunya, and may regulate pathways important in initial infection, replication, and systemic response to SARS-CoV-2. We present a series of four high-risk, symptomatic, COVID-19+ patients, with known pulmonary disease, treated with doxycycline with subsequent rapid clinical improvement. No safety issues were noted with use of doxycycline.Doxycycline is an attractive candidate as a repurposed drug in the treatment of COVID-19 infection, with an established safety profile, strong preclinical rationale, and compelling initial clinical experience described here.The reviews of this paper are available via the supplemental material section.

Advanced Pulmonary Sarcoidosis.

At least 5% of sarcoidosis patients die from their disease, usually from advanced pulmonary sarcoidosis. The three major problems encountered in advanced pulmonary sarcoidosis are pulmonary fibrosis, pulmonary hypertension, and respiratory infections. Pulmonary fibrosis is the result of chronic inflammation, but other factors including abnormal wound healing may be important. Sarcoidosis-associated pulmonary hypertension (SAPH) is multifactorial including parenchymal fibrosis, vascular granulomas, and hypoxia. Respiratory infections can be cause by structural changes in the lung and impaired immunity due to sarcoidosis or therapy. Anti-inflammatory therapy alone is not effective in most forms of advanced pulmonary sarcoidosis. New techniques, including high-resolution computer tomography and 18F-fluorodeoxyglucose positron emission tomography (PET) have proved helpful in identifying the cause of advanced disease and directing specific therapy.

Advanced pulmonary sarcoidosis.

PURPOSE OF REVIEW: Mortality in patients with sarcoidosis has primarily been attributed to advanced pulmonary sarcoidosis. This review aims to provide an update on recent clinical studies that help to better phenotype these patients, discuss new treatment options, and suggest areas where additional research is needed. RECENT FINDINGS: Diagnosis and management of advanced pulmonary sarcoidosis has changed as new technologies and treatment options have emerged. Clinical phenotypes of advanced disease have evolved to show overlap in presentation with other interstitial lung diseases. Assessment involves more advanced imaging modalities. New promising treatment options are being studied. Pulmonary rehabilitation and lung transplantation are being utilized to improve health-related quality of life and survival. SUMMARY: Patients with advanced pulmonary fibrosis can have variable clinical, radiographic, histopathologic presentation. Given the poor health-related quality of life and high rates of mortality, medical therapy and pulmonary rehabilitation may benefit these patients. Lung transplantation should be considered in those with end-stage disease.

Clinical features and outcomes of asymptomatic pulmonary sarcoidosis. A comparative cohort study.

OBJECTIVE: To evaluate the clinical characteristics and outcomes of patients with asymptomatic pulmonary sarcoidosis (APS) detected incidentally and compare them with symptomatic non-Löfgren sarcoidosis (SnLS) patients. METHODS: Patients diagnosed as having APS at a University hospital in Barcelona, Spain, followed prospectively from 1976 to 2018. APS was defined as the presence of bilateral hilar lymphadenopathy (BHL) with or without lung parenchymal involvement discovered incidentally on chest radiograph or CT scan. APS was compared with SnLS. RESULTS: APS was diagnosed in 50 (13.6%) and SnLS in 317 (86.4%) patients. At diagnosis, stage I chest radiograph was significantly more frequent in APS than in SnLS (p < 0.001) and there were no asymptomatic patients with stages III and IV. SnLS showed more severe impairment in FVC (p = 0.009) and forced expiratory volume in 1st second (FEV1) (p = 0.003) than APS, while DLco was similar in both groups. Extrathoracic involvement at diagnosis and during the follow up was less frequent in APS than in SnLS patients (p < 0.005). Endobronchial ultrasonography-guided transbronchial needle aspiration (EBUS) was the most used diagnostic tool. Treatment was more frequently required in the SnLS than in APS (p < 0.001). At five years, APS patients showed less presence of active disease than SnLS (p = 0.054). CONCLUSIONS: APS showed earlier radiological stages, lesser impairment in lung function, extrapulmonary organ involvement and need for treatment than SnLS. EBUS was the most useful diagnostic tool. In spite of its benign presentation, around one third of patients evolved to persistent disease but usually with mild clinical and functional impairment.

Therapeutic strategies for pulmonary sarcoidosis.

Introduction: The treatment of pulmonary sarcoidosis is not standardized. Treatment involves a multi-step decision process beginning with whether treatment is warranted, determining initial therapy, then assessing when therapy requires modifications or can be discontinued.Areas covered: This manuscript will address the following issues concerning the treatment of pulmonary sarcoidosis: Treatment indications, initial anti-granulomatous therapy, therapy for chronic and fibrotic disease, glucocorticoid therapy, alternative therapy to glucocorticoids, non-granulomatous therapies, and managing complications of disease. Information was obtained through a literature search of PubMed and Web of Science databases.Expert opinion: Although glucocorticoids are highly effective for pulmonary sarcoidosis, their potential to cause significant side effects often mandates consideration of alternative agents. As the most common indication for the treatment of pulmonary sarcoidosis is quality of life impairment, traditional objective tests of lung function and radiographic imagining often have a minor role in therapeutic decision-making. The development of pulmonary fibrosis from sarcoidosis often causes major morbidity and mortality and should be a major focus of concern.

[Diagnostics and Treatment of Cardiac Sarcoidosis - Consensus Paper of the German Respiratory Society (DGP) and the German Cardiac Society (DGK)]. / Diagnostik und Therapie der kardialen Sarkoidose.

Sarcoidosis is a multisystemic granulomatous disorder which affects the respiratory system in the majority of the cases. Symptomatic cardiac manifestations are found in less than 10 % of the affected cohorts and show a large heterogeneity based on the ethnic background. Cardiac sarcoidosis is not only found in patients with rhythmogenic heart disease, such as atrial and ventricular fibrillation but also in all phenotypes of cardiomyopathy. The overall morbidity and mortality caused by cardiac sarcoidosis in Germany remains unclear and large prospective international observational studies.underline the importance of this disease entity. This consensus paper on diagnostic and therapeutic algorithms for cardiac sarcoidosis is based on a current literature search and forms an expert opinion statement under the auspices of the German Respiratory Society and the German Cardiac Society. The rationale of this statement is to provide algorithms to facilitate clinical decision-making based on the individual case situation.

Psychological burden associated with worse clinical outcomes in sarcoidosis.

Introduction: Sarcoidosis is a multisystem granulomatous inflammatory disorder. Sarcoidosis is associated with significant morbidity and rising healthcare utilisation. Patients with sarcoidosis report higher psychological symptoms than the general population. We evaluated the association between depressive and anxiety symptoms and clinical outcomes in patients with pulmonary sarcoidosis requiring treatment. Methods: Adult patients in the Johns Hopkins Sarcoidosis Clinic diagnosed with pulmonary sarcoidosis on treatment were eligible for enrollment. Questionnaires were administered to assess depressive and anxiety symptoms, healthcare utilisation and health-related quality of life (HRQoL). Results: 112 participants were enrolled (57% women, 53% African American, median age: 57 years). 34% of participants screened positive for mild and 20% for moderate-severe depressive symptoms. 25% of participants screened positive for mild and 12% for moderate-severe anxiety symptoms. Participants with moderate-severe psychological symptoms had a higher odds of an emergency department visit in the previous 6 months (8.87 for depressive symptoms and 13.05 for anxiety symptoms) and worse HRQoL compared with participants without psychological symptoms. Participants with moderate-severe depressive symptoms had lower diffusion capacity of the lungs for carbon monoxide % predicted compared with those without depressive symptoms. There was no association between elevated psychological symptoms and the odds of hospitalisation, forced vital capacity % predicted and forced expiratory volume in 1 second % predicted. Conclusion: Psychological symptoms may be associated with worse clinical outcomes in sarcoidosis. Improving the recognition through clinic screening and referral for treatment of depression and anxiety in sarcoidosis may reduce acute healthcare utilisation and improve HRQoL.

Pre-operative therapeutic plasma Exchange and intravenous immune globulin for the treatment of heparin induced thrombocytopenia in a lung transplant recipient.

Lung transplantation surgery often relies on the use of intraoperative extracorporeal membrane oxygenation (ECMO) and necessitates the need for high dose anticoagulation. Heparin induced thrombocytopenia complicates intraoperative anticoagulation management during lung transplant surgery requiring ECMO. Though other anticoagulants such as argatroban and bivalrudin are utilized for the treatment of Heparin Induced Thrombocytopenia (HIT), the lack of reversal agents makes it difficult to use these agents intraoperatively in cases with high bleeding risk. This is especially true in patients with end stage fibrotic lung disease with calcified mediastinal lymphadenopathy and pulmonary hypertension undergoing lung transplantation. Here we describe a case of HIT in a patient with Sarcoidosis listed for lung transplant who was treated with Therapeutic Plasma Exchange and Intravenous Immune globulin preoperatively and successfully underwent lung transplantation with the use of intraoperative venoarterial ECMO and heparin anticoagulation.

Contemporary optimized practice in the management of pulmonary sarcoidosis.

Pulmonary sarcoidosis is the most common form of sarcoidosis, accounting for the initial presentation in over 70% patients and with eventual presence in 90% of patients with sarcoidosis. However, the course of the disease is often unpredictable; its manifestations can be highly variable and its treatment may not be effective in all patients. As such, the optimized treatment of pulmonary sarcoidosis often requires a thoughtful personalized approach with the need to get the patient involved in decisions of management. In many patients with pulmonary sarcoidosis, the disease is self-limited and nonprogressive, thus treatment is not necessary. In other patients, the presence of significant symptoms or functional limitation often associated with worsening radiological changes and pulmonary function tests warrants treatment. Corticosteroids are the first-line treatment for pulmonary sarcoidosis; antimetabolites are second-line agents, with methotrexate being most commonly employed. Antitumor necrosis alpha antibodies, especially infliximab, are emerging as potential third-line agents. A high index of suspicion should be held for pulmonary hypertension and other comorbidities that may complicate the course of patients with advanced sarcoidosis. Lung transplantation may be the only option for patients who have refractory disease despite maximal medical therapy.

Moving target: shifting the focus to pulmonary sarcoidosis as an autoimmune spectrum disorder.

Despite more than a century of research, the causative agent(s) in sarcoidosis, a heterogeneous granulomatous disorder mainly affecting the lungs, remain(s) elusive. Following identification of genetic factors underlying different clinical phenotypes, increased understanding of CD4+ T-cell immunology, which is believed to be central to sarcoid pathogenesis, as well as the role of B-cells and other cells bridging innate and adaptive immunity, contributes to novel insights into the mechanistic pathways influencing disease resolution or chronicity. Hopefully, new perspectives and state-of-the-art technology will help to shed light on the still-elusive enigma of sarcoid aetiology. This perspective article highlights a number of recent advances in the search for antigenic targets in sarcoidosis, as well as the main arguments for sarcoidosis as a spectrum of autoimmune conditions, either as a result of an external (microbial) trigger and/or due to defective control mechanisms regulating the balance between T-cell activation and inhibition.

Paediatric sarcoidosis.

Paediatric sarcoidosis is an extremely rare disease characterized by a granulomatous inflammation. The estimated incidence is 0.6-1.02/100,000 children, but in the absence of international registers, the disease is probably under-reported. Its pathophysiologic basis is not clearly understood but the current hypothesis is a combination of a genetic predisposition and an environmental exposure that could be either organic or mineral. Contrary to adult forms of the disease, general symptoms are often at the forefront at diagnosis. In its most frequent form, paediatric sarcoidosis is a multi-organ disorder affecting preferentially the lungs, the lymphatic system and the liver, but all organs can be affected. This review aims to provide an overview of current knowledge on sarcoidosis in children, providing a summary of the data available from cohort studies on the presentation, the management and the evolution of the disease in this specific population.

Interstitial Lung Diseases in Developing Countries.

More than 100 different conditions are grouped under the term interstitial lung disease (ILD). A diagnosis of an ILD primarily relies on a combination of clinical, radiological, and pathological criteria, which should be evaluated by a multidisciplinary team of specialists. Multiple factors, such as environmental and occupational exposures, infections, drugs, radiation, and genetic predisposition have been implicated in the pathogenesis of these conditions. Asbestosis and other pneumoconiosis, hypersensitivity pneumonitis (HP), chronic beryllium disease, and smoking-related ILD are specifically linked to inhalational exposure of environmental agents. The recent Global Burden of Disease Study reported that ILD rank 40th in relation to global years of life lost in 2013, which represents an increase of 86% compared to 1990. Idiopathic pulmonary fibrosis (IPF) is the prototype of fibrotic ILD. A recent study from the United States reported that the incidence and prevalence of IPF are 14.6 per 100,000 person-years and 58.7 per 100,000 persons, respectively. These data suggests that, in large populated areas such as Brazil, Russia, India, and China (the BRIC region), there may be approximately 2 million people living with IPF. However, studies from South America found much lower rates (0.4-1.2 cases per 100,000 per year). Limited access to high-resolution computed tomography and spirometry or to multidisciplinary teams for accurate diagnosis and optimal treatment are common challenges to the management of ILD in developing countries.

A 31-Year-Old Man With Airflow Obstruction, Intrathoracic Adenopathy, and Pulmonary Nodules.

CASE PRESENTATION: A 31-year-old white man presented for evaluation of productive cough and dyspnea on exertion of 2 months' duration. Associated symptoms included wheezing, chest tightness, and postnasal drip. He was recently treated for pneumonia with a 7-day course of levofloxacin because of an abnormal chest radiograph demonstrating bilateral infiltrates, but his symptoms failed to improve. He had a medical history of mild intermittent asthma and was on no active treatment. He was a nonsmoker. He was born in the United States. He denied any recent travel within or outside the United States, sick contacts, or illicit drug use. He did not have any pets and denied exposure to mold, hot tubs, a down comforter, or pillows. He worked in a vocational program and his hobbies included refinishing wood floors.

Atypical CT findings of pulmonary sarcoidosis: A case report.

RATIONALE: Pulmonary involvement occurs in about 90% of patients with sarcoidosis. However, delayed diagnosis sometimes occurs due to atypical thoracic imaging findings. PATIENT CONCERNS: A 52-year-old woman presented with recurrent uveitis and fever of unknown origin. She had been admitted to the hospital due to fever, but its cause was not determined. DIAGNOSES: Chest computed tomography (CT) revealed a solitary pulmonary nodule and an enlarged right axillary lymph node. The nodule had showed an interval growth from 0.7 cm to 1.1 cm over 18 months, when compared to the previous chest CT. Mosaic attenuation was also observed. INTERVENTIONS: The patient underwent thoracoscopic wedge resection of the nodule and excisional biopsy of the enlarged lymph node to exclude malignancy and non-caseating granulomas consistent with sarcoidosis was confirmed. OUTCOMES: Medical treatment with prednisolone and azathioprine was administered. Fever and uveitis no longer recurred after 6 months of medication. We demonstrated that sarcoidosis shows only atypical pulmonary imaging findings, with an enlarged solitary nodule, an axillary lymphadenopathy, and mosaic attenuation, mimicking a malignancy. LESSONS: Awareness on atypical CT manifestations that are correlated with pathologic findings may be helpful for early diagnosis of sarcoidosis.

White donor, younger donor and double lung transplant are associated with better survival in sarcoidosis patients.

Sarcoidosis commonly affects the lung. Lung transplantation (LT) is required when there is a severe and refractory involvement. We compared post-transplant survival rates of sarcoidosis patients with chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). We also explored whether the race and age of the donor, and double lung transplant have any effect on the survival in the post transplant setting. We analyzed 9,727 adult patients with sarcoidosis, COPD, and IPF who underwent LT worldwide between 2005-2015 based on United Network for Organ Sharing (UNOS) database. Survival rates were compared with Kaplan-Meier, and risk factors were investigated by Cox-regression analysis. 469 (5%) were transplanted because of sarcoidosis, 3,688 (38%) for COPD and 5,570 (57%) for IPF. Unadjusted survival analysis showed a better post-transplant survival rate for patients with sarcoidosis (p < 0.001, Log-rank test). In Cox-regression analysis, double lung transplant and white race of the lung donor showed to have a significant survival advantage. Since double lung transplant, those who are younger and have lower Lung Allocation Score (LAS) at the time of transplant have a survival advantage, we suggest double lung transplant as the procedure of choice, especially in younger sarcoidosis subjects and with lower LAS scores.