European Respiratory Society
Sarcoidosis

Recent reports indicate that the prevalence of sarcoidosis is rising and mortality in chronic sarcoidosis patients is increasing. With myriad clinical manifestations, and multi-system involvement, there is a need for all clinicians to have a working knowledge of the condition. This Monograph provides a comprehensive overview of the most recent advances in sarcoidosis. Opening with chapters on history, epidemiology and pathobiology, it goes on to provide in-depth coverage of: specific organ manifestations and general diagnostic pathways; traditional as well as innovative treatment strategies; and, importantly, patient quality-of-life assessment. This book will be useful to clinicians around the world.

  1. Page v
  2. Page vii
  3. Page x
  4. Page 1
    Abstract
    Corresponding author: Ulrich Costabel (ulrich.costabel@ruhrlandklinik.uk-essen.de)

    The definition of sarcoidosis has changed over time. The histological hallmarks of granuloma, unknown cause and multisystem involvement emerged as the three essential defining features, and later the heightened Th1 immune response at sites of disease was added. The history of sarcoidosis started >150 years ago with early observations made on patients with skin disease. By 1915, the systemic nature of sarcoidosis became evident. Since the 1940s, our knowledge of the disease including potential causes, epidemiology, immunology, genetics and clinical presentation has undergone remarkable changes. The history of the immunology of sarcoidosis is a good example of the change of dogmas in our understanding of disease concepts. In the 1960s, the dogma was that sarcoidosis is a disease of decreased immune functions. With the use of BAL as a research tool since the 1970s, the concept changed to a disease of immunological hyperresponsiveness characterised by an exaggerated Th1 immune response at sites of disease activity.

    Cite as: Costabel U, Nagai S. Definition and history. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 1–7 [https://doi.org/10.1183/2312508X.10031020].

  5. Page 8
    Abstract
    Corresponding author: Yvette C. Cozier (yvettec@bu.edu)

    Sarcoidosis is a rare, clinically heterogeneous disease, making the identification of a single aetiological candidate challenging. Epidemiological research into the aetiology of sarcoidosis has been hampered by variability of case definition, heterogeneity of organ involvement, and numerous other variables. The global burden of sarcoidosis is not fully appreciated as there is considerable geographic variability including numerous countries for which there are no data. While sarcoidosis can strike at any age, recent data support a later onset of disease, with the average age ranging from 46 to 51 years and an increasing percentage of cases occurring after age 65 years. Data also suggest that prolonged exposure to an infectious agent or inorganic antigen may not be required to trigger an immunological cascade, further complicating efforts to establish associations between sarcoidosis and complex environments. Taken together, these findings provide a knowledge base for future discovery.

    Cite as: Cozier YC, Arkema EV, Rodriguez JV, et al. Epidemiology: solving the jigsaw puzzle. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 8–24 [https://doi.org/10.1183/2312508X.10031120].

  6. Page 25
    Abstract
    Corresponding author: Johan Grunewald (johan.grunewald@ki.se)

    In the last decade, our knowledge of sarcoidosis pathobiology has improved substantially, yet its aetiology remains elusive. Immunological features of sarcoidosis include, among others, enhanced expression of Th1 (and often Th17) cytokines at disease sites, abnormal regulatory T-cell responses, oligoclonal expansion of CD4+ T-cells consistent with persistent antigen exposure and granuloma formation. An emerging body of literature suggests that B-cells and antibody responses may also be involved in disease pathogenesis. Multiple environmental agents have been associated with sarcoidosis, including mycobacterial or propionibacterial organisms, but the mechanisms through which microbial infection may cause sarcoidosis remain speculative. Identification of the inciting agent(s) and insight into the immunological events that determine granuloma formation and evolution to fibrosis will inevitably facilitate the development of more efficacious therapies.

    Cite as: Spagnolo P, Grunewald J. Aetiopathogenesis, molecular determinants and immunological features. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 25–40 [https://doi.org/10.1183/2312508X.10015621].

  7. Page 41
    Abstract
    Corresponding author: Coline H.M. van Moorsel (c.van.moorsel@antoniusziekenhuis.nl)

    Sarcoidosis is a heterogeneous disease with significant heritability and a significant proportion of familial disease, providing convincing evidence for a role of genetic factors in disease development. Numerous genes have been shown to be involved in the risk for disease development and its phenotypic manifestations. So far, strong genetic associations have been detected only for specific ethnic and phenotypic populations and involve the HLA class II-encoding peptides that are important for antigen recognition, and may thus be disease trigger related. Many of the genomic regions and genes that have been shown to associate with sarcoidosis significantly overlap with those identified for a wide spectrum of immune-mediated diseases, while only a few are specific for sarcoidosis or a phenotype of the disease. Although recent whole-exome sequencing approaches have not yet provided easily interpretable results, such unbiased deep-sequencing methods hold promise for further unravelling of the immunopathogenic pathways underlying the different disease entities in sarcoidosis.

    Cite as: van Moorsel CHM, Petrek M, Rivera NV. Unravelling the genetic basis of sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 41–56 [https://doi.org/10.1183/2312508X.10031320].

  8. Page 57
    Abstract
    Corresponding author: Rocco Trisolini (rocco.trisolini@policlinicogemelli.it)

    The diagnosis of sarcoidosis is tentative and has a higher likelihood of being correct if a compatible clinical and radiological presentation is supported by evidence of non-necrotising granulomatous inflammation in at least one organ/tissue. However, some clinical scenarios (Löfgren syndrome, Heerfordt syndrome, lupus pernio, and asymptomatic bilateral hilar lymphadenopathy) are thought to be so specific that they allow a presumptive diagnosis of sarcoidosis to be established without a biopsy. When histological confirmation of the clinical suspicion is needed and an easily accessible superficial lesion is lacking, bronchoscopy with its ancillary sampling techniques is commonly performed, because the thorax is involved in the vast majority (>90%) of sarcoidosis patients. The exclusion of alternative diagnoses is imperative, even when pathological examination of the biopsy sample reveals a non-necrotising granulomatous inflammation, as several infectious, inflammatory and even malignant conditions (i.e. lymphomas) may have a granulomatous component.

    Cite as: Trisolini R, Spagnolo P, Baughman RP. Principles of diagnosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 57–74 [https://doi.org/10.1183/2312508X.10031420].

  9. Page 75
    Abstract
    Corresponding author: Rémy L.M. Mostard (r.mostard@zuyderland.nl)

    Imaging contributes to the diagnosis of sarcoidosis and the exclusion of other causes of granulomatous disorders, is useful in detecting disease complications, provides prognostic information, and is an important factor in treatment decisions. In clinical practice, conventional imaging techniques, such as chest radiography and HRCT, are part of the routine work-up in sarcoidosis. Certain HRCT patterns are highly specific for the diagnosis of sarcoidosis, whereas other features are typical for potentially reversible or, on the contrary, fibrotic disease. Although not indicated in the routine work-up, imaging techniques such as MRI and PET can be of major added value in the evaluation of the extent of disease. PET can also help establish the presence of inflammatory activity in specific patient populations, including those with suspected sarcoidosis, those with unexplained persistent disabling symptoms, and those with (suspected) cardiac sarcoidosis. Furthermore, PET can provide prognostic information and can be useful in monitoring treatment effect.

    Cite as: Mostard RLM, Yadav R. Conventional and nuclear imaging techniques. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 75–90 [https://doi.org/10.1183/2312508X.10031520].

  10. Page 91
    Abstract
    Corresponding author: Giulio Rossi (giurossi68@gmail.com)

    Pathologists are frequently involved in the diagnosis of sarcoidosis when tissue specimens are required to confirm the presence of sarcoid granulomas. In general, this occurs when the clinical and imaging features are atypical for sarcoidosis. In this setting, evaluation of granulomas in the lung is related to their qualitative characteristics (well-formed aggregate of epithelioid histiocytes lacking necrosis and surrounded by few lymphocytes and fibrotic tissue) and anatomic involvement (lymphatic distribution along the subpleural space, the interlobular septa and around the bronchovascular bundles). The pathological differential diagnoses mainly include infections, hypersensitivity pneumonitis, autoimmune diseases and a drug reaction, particularly with novel immunotherapeutic agents. Transbronchial biopsy/fine-needle aspiration of the lung parenchyma and/or mediastinal lymph nodes usually results in an accurate final diagnosis when interpreted within the appropriate clinical, laboratory and radiological findings.

    Cite as: Rossi G, Farver C. Pathological features and differential diagnosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 91–106 [https://doi.org/10.1183/2312508X.10031620].

  11. Page 107
    Abstract
    Corresponding author: Jan C. Grutters (j.grutters@antoniusziekenhuis.nl)

    Over the last 10 years, a range of biomarkers have been evaluated in sarcoidosis. Based on extensive literature reviews over this period, the single serum analytes serum ACE, soluble IL-2 receptor and chitotriosidase stand out as potential diagnostic and monitoring tools with significant sensitivity and specificity, although none functions alone as a gold standard biomarker. Other proteins, such as YKL-40, Krebs von den Lungen-6, cathepsin S and IFN-γ-induced protein 10, show potential as biomarkers. Unfortunately, data on serum biomarkers for use as a prognostic tool (to predict disease outcome, irrespective of treatment) or as a predictive tool (to predict the effect of therapy) are scarce. With respect to imaging modalities as biomarkers, 18F-FDG PET seems to have potential as a prognostic tool. This nuclear biomarker may also help in determining treatable inflammatory lesions in symptomatic patients with indecisive conventional tests. Future research on biomarkers, including those emerging from novel technologies, as well as the utility of combined biomarkers, should rely on carefully designed prospective trials to allow translation and implementation in routine clinical care.

    Cite as: Korenromp IHE, Maier LA, Grutters JC. Serum and imaging biomarkers. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 107–121 [https://doi.org/10.1183/2312508X.10031720].

  12. Page 122
    Abstract
    Corresponding author: Francesco Bonella (francesco.bonella@rlk.uk-essen.de)

    The lung is the most common organ affected by sarcoidosis. Multiple tools are available to assist clinicians in assessing lung disease activity and in excluding alternative causes of respiratory symptoms. Improving outcomes in pulmonary sarcoidosis should focus on preventing disease progression and disability, and preserving quality of life, in addition to timely identification and management of complications like fibrotic pulmonary sarcoidosis. While steroids continue to be first-line therapy, other therapies with fewer long-term side-effects are available and should be considered in certain circumstances. Knowledge of common clinical features of pulmonary sarcoidosis and specific pulmonary sarcoidosis phenotypes is important for identifying patients who are more likely to benefit from treatment.

    Cite as: James WE, Bonella F. Pulmonary sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 122–141 [https://doi.org/10.1183/2312508X.10031820].

  13. Page 142
    Abstract
    Corresponding author: David H. Birnie (DBirnie@ottawaheart.ca)

    It is estimated that 20–25% of systemic sarcoidosis patients have clinically silent cardiac involvement. Approximately 5–10% will have clinically overt cardiac involvement presenting with major arrhythmias (conduction abnormalities, ventricular arrhythmias) and/or new-onset unexplained heart failure. Such cardiac presentations (and even sudden cardiac death) can be the first manifestation of cardiac sarcoidosis (CS). While cardiac MRI is the gold standard for identifying myocardial fibrosis, 18F-FDG PET is used to detect active myocardial inflammation and guide immunosuppression. Treatment in CS is multidisciplinary and includes immunosuppression and heart-failure and anti-arrhythmic medications and/or devices, typically implantable cardioverter defibrillators (ICDs). Immunosuppression focuses on the elimination of myocardial inflammation with conflicting evidence about the impact on disease evolution. The extent of left ventricular dysfunction is the most important predictor of outcome among patients with CS. The prognosis for CS is much improved in the current era of earlier diagnosis, modern heart-failure treatment and use of ICD therapy.

    Cite as: Birnie DH, Kouranos V. Cardiac sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 142–159 [https://doi.org/10.1183/2312508X.10031920].

  14. Page 160
    Abstract
    Corresponding author: Jinny Tavee (taveej@njhealth.org)

    Neurological complications of sarcoidosis include not only granulomatous disease but also nongranulomatous disorders such as small-fibre neuropathy (SFN) and headache. This chapter reviews the clinical manifestations of both types of disorder as well as updated diagnostic criteria, and describes newer diagnostic studies including SFN testing and details regarding current treatment options. In the last few years, there have been several reports demonstrating the beneficial effects of infliximab in treating neurosarcoidosis. Similarly, intravenous immunoglobulins may be helpful with sarcoidosis-associated SFN.

    Cite as: Tavee J, Voortman M. Granulomatous and nongranulomatous neurological sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 160–173 [https://doi.org/10.1183/2312508X.10032020].

  15. Page 174
    Abstract
    Corresponding author: Misha Rosenbach (Misha.Rosenbach@pennmedicine.upenn.edu)

    Cutaneous involvement is present in one-quarter of sarcoidosis patients. In some patients the skin may be minimally affected; in others it may serve as a sign of systemic disease activity; and in a subset of patients, cutaneous sarcoidosis may be the primary manifestation of the disease. Skin disease can be uncomfortable, disfiguring and have a profound impact on patients and quality of life. Cutaneous lesions may also serve as readily accessible, low-risk sites for tissue biopsy and histological evidence of granulomatous disease, and the ability to recognise and diagnose sarcoidosis in the skin is essential for all clinicians caring for patients with the disease.

    Cite as: Murphy C, Marcoval J, Mañá J, et al. Cutaneous sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 174–192 [https://doi.org/10.1183/2312508X.10032120].

  16. Page 193
    Abstract
    Corresponding author: Robert P. Baughman (BAUGHMRP@ucmail.uc.edu)

    Sarcoidosis can lead to abnormal calcium metabolism in up to one-quarter of patients. This can lead to hypercalcaemia and nephrocalcinosis. Both of these may lead to renal dysfunction. Direct renal involvement from sarcoidosis occurs in a smaller proportion of patients. Granulomatous interstitial nephritis has been associated with hypercalcaemia. The interaction between calcium and renal dysfunction should be evaluated in all sarcoidosis patients as part of their initial evaluation and on a regular basis as clinically indicated. Bone health in sarcoidosis patients can be impacted by abnormal calcium metabolism and anti-inflammatory therapy, especially glucocorticoids. Evaluation of the calcium–kidney–bone axis is an important aspect of the management of sarcoidosis.

    Cite as: Baughman RP, Lower EE. The calcium–kidney–bone axis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 193–205 [https://doi.org/10.1183/2312508X.10032220].

  17. Page 206
    Abstract
    Corresponding author: Marlies S. Wijsenbeek (m.wijsenbeek-lourens@erasmusmc.nl)

    Non-organ-specific manifestations such as fatigue, anxiety, depression, pain, cognitive dysfunction and small-fibre neuropathy are common in patients with sarcoidosis. These symptoms do not usually require immunosuppressive therapy and often persist, even while there are no signs of organ-specific sarcoidosis activity. These invisible manifestations of sarcoidosis often have significant impact on health-related quality of life, and therefore should be adequately addressed and not be overlooked. In this chapter, we summarise the current literature about non-organ manifestations, including their prevalence, impact, assessment and treatment. Subsequently, we advocate a multidisciplinary and overarching approach for management and discuss future directions.

    Cite as: Kahlmann V, Patel DC, Marts LT, et al. Non-organ-specific manifestations. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 206–222 [https://doi.org/10.1183/2312508X.10032320].

  18. Page 223
    Abstract
    Corresponding author: Nabeel Hamzeh (nabeel-hamzeh@uiowa.edu)

    Hepatic and splenic sarcoidosis are detected clinically in about 10% of sarcoidosis patients but are asymptomatic in up to 79% of cases. Splenic involvement is usually asymptomatic, and hepatic involvement can vary from asymptomatic to showing nonspecific symptoms to presenting with signs and symptoms of cirrhosis and portal hypertension. Diagnostic criteria mainly rely on compatible clinical variables in the setting of established sarcoidosis, and occasionally on pathological findings. The differential diagnosis for both hepatic and splenic involvement is wide, and careful assessment is needed to avoid misdiagnosis, as sarcoidosis is a diagnosis of exclusion. Various imaging modalities reveal organ enlargement and nodularity, but the findings are not pathognomonic for sarcoidosis. Treatment is indicated in symptomatic cases and when there is evidence of significant organ dysfunction. Ursodeoxycholic acid is a therapeutic option in predominantly hepatic sarcoidosis, and splenic and hepatic involvement tend to respond to standard anti-sarcoidosis regimens. Careful monitoring for potential complications is imperative. Liver transplantation has been successful in cases of end-stage liver disease due to sarcoidosis.

    Cite as: Jeny F, Hamzeh N. Hepatic and splenic involvement. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 223–233 [https://doi.org/10.1183/2312508X.10032820].

  19. Page 234
    Abstract
    Corresponding author: Oksana A. Shlobin (oksana.shlobin@inova.org)

    Sarcoidosis-associated pulmonary hypertension (SAPH) is a common complication of pulmonary sarcoidosis that contributes to increased symptoms of dyspnoea and morbidity and decreased survival. The mechanisms by which SAPH develops are complex, multifactorial and often overlapping. There remain many unknowns regarding the pathogenesis, natural history and effective treatment of this disease. Over the past decade, a growing body of literature has provided additional insights that have helped the medical community to better characterise and treat this disease. This chapter aims to summarise both the previous literature and the most recent developments in SAPH.

    Cite as: Khangoora V, Nunes H, Shlobin OA. Sarcoidosis-associated pulmonary hypertension. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 234–255 [https://doi.org/10.1183/2312508X.10032920].

  20. Page 256
    Abstract
    Corresponding author: Peter Korsten (peter.korsten@med.uni-goettingen.de)

    Musculoskeletal complaints are commonly present in sarcoidosis and can range from nonspecific arthralgias and myalgias to well-defined findings, such as overt arthritis, sacroiliitis, bone sarcoidosis or myositis. Further adding to the complexity of the disease, sarcoidosis may mimic other rheumatic diseases that need to be ruled out before a diagnosis of sarcoidosis can be made. A frequent presentation is Löfgren syndrome (erythema nodosum, bilateral ankle periarthritis and bilateral hilar lymphadenopathy). To control Löfgren syndrome, anti-inflammatory drugs are often required, but the prognosis is usually good. Chronic sarcoidosis can involve the joints with arthritis, dactylitis, bone sarcoidosis or sacroiliitis. Therefore, treatment decisions need to take into consideration which organ systems are affected and require treatment. While no therapies are approved explicitly for sarcoid arthritis, glucocorticoids and disease-modifying anti-sarcoid drugs (conventional or biological) are used sequentially as needed to control symptoms.

    Cite as: Korsten P, Sweiss NJ. Rheumatological manifestations. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 256–266 [https://doi.org/10.1183/2312508X.10033020].

  21. Page 267
    Abstract
    Corresponding author: Pascal Sève (pascal.seve@chu-lyon.fr)

    Sarcoidosis is one of the leading causes of inflammatory eye disease. All ocular structures can be affected but uveitis and optic neuropathy are the two main manifestations responsible for vision loss in ocular sarcoidosis. Typical sarcoid anterior uveitis presents with mutton-fat keratic precipitates, iris nodules and posterior synechiae. Posterior involvement includes vitritis, vasculitis and choroidal lesions. Cystoid macular oedema is the most important and sight-threatening consequence of sarcoid uveitis. Patients with clinically isolated uveitis at diagnosis rarely develop other organ involvement. Even though ocular sarcoidosis can have a severe impact on visual prognosis, early diagnosis and a wider range of available therapies (including intravitreal implants) have lessened the functional impact of the disease, particularly in the last decade. Corticosteroids are the cornerstone of treatment for sarcoidosis but up to 30% of patients achieve remission requiring high dosages of systemic steroids. In these cases, the use of steroid-sparing immunosuppressive therapy (such as MTX) is unavoidable. Among these immunosuppressive treatments, anti-TNF-α drugs have been a revolution in the management of noninfectious uveitis.

    Cite as: Giorgiutti S, Serrar Y, El-Jammal T, et al. Ocular sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 267–284 [https://doi.org/10.1183/2312508X.10033120].

  22. Page 285
    Abstract
    Corresponding author: Nadia Nathan (nadia.nathan@aphp.fr)

    Sarcoidosis is very rare in children, with an estimated prevalence of 0.40–0.80 per 100 000 children. Teenagers are more affected, but the disease can be observed in children of all ages. The pathophysiology of paediatric sarcoidosis is likely to be similar to that of adults, including an aberrant inflammatory and granulomatous response to an antigenic trigger (organic or mineral, especially dusts) in genetically predisposed patients (genes involved in autophagy and mitophagy). The disease is often severe at presentation, with general signs (fever, weight loss, asthenia) and multiorgan involvement, with the lungs, liver and eyes predominantly affected. Diagnosis requires an exhaustive workup to exclude other causes of granulomatous disorders. Corticosteroids are the first-line treatment, either orally or intravenously (high-dose pulses) for months to years, with immunosuppressive drugs as a second-line treatment. The course of sarcoidosis is unpredictable, and relapses are frequent in adulthood. This argues for long-term follow-up of patients and an optimal transition of care from paediatric to adult departments.

    Cite as: Nathan N, Hadchouel A. Paediatric sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 285–294 [https://doi.org/10.1183/2312508X.10033220].

  23. Page 295
    Abstract
    Corresponding author: Marc A. Judson (judsonm@mail.amc.edu)

    Sarcoidosis is a multisystem granulomatous disease that can affect any organ. However, several organs are rarely involved with the disease, and are reviewed in this chapter. The specific manifestations of sarcoidosis in these organs are discussed in detail. Although organs that are rarely involved with sarcoidosis often cause no symptoms and usually do not require treatment, there is often the possibility that an alternative condition is present such as an infection or malignancy that mandates that a diagnostic biopsy be performed. Therefore, adequate management of rare organ involvement with sarcoidosis requires knowledge of alternative potential diagnoses that need to be excluded. When treatment is required for rare organ involvement with sarcoidosis, typical sarcoidosis therapy is usually sufficient.

    Cite as: Judson MA, Pastre J, Israël-Biet D. The manifestations of rare organ sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 295–315 [https://doi.org/10.1183/2312508X.10033320].

  24. Page 316
    Abstract
    Corresponding author: Daniel A. Culver (culverd@ccf.org)

    Sarcoidosis treatment is initiated for two major reasons: threat of severe organ dysfunction (danger) or to improve quality of life when bothersome symptoms dominate the presentation. While there are few data to suggest a major impact of treatment on the likelihood of long-term disease remission, reducing inflammation with prednisone and other therapies is likely to prevent progressive, organ-threatening disease, and may be useful to restore symptomatic organ dysfunction. As most death and major morbidity from sarcoidosis occur in patients with extensive pulmonary disease, pulmonary hypertension, cardiac sarcoidosis, neurological disease, uveitis and calcium derangements, danger indications for treatment are typically present when these organs are substantially affected. Management involves prognostic assessment of the likely natural history of the disease and often entails relatively aggressive immunosuppressive therapy, with a more proscriptive role for the physician in the decision to treat. In contrast, treatment of bothersome symptoms typically revolves around a patient-centred, individualised discussion, considering the relationship of the symptoms to granulomatous inflammation, likelihood of response to therapy and risks of medications. Therapy may be much less aggressive when treating quality of life. Corticosteroid therapy is associated with significant toxicity, probably accounting for a proportion of sarcoidosis mortality. Longitudinal care of the patient includes recurring assessments of the risk–benefit balance of treatment, likelihood of remission, screening for new evidence of dangerous sarcoidosis and consideration of emergent comorbidities.

    Cite as: Culver DA, Wells AU. When to treat sarcoidosis. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 316–327 [https://doi.org/10.1183/2312508X.10033520].

  25. Page 328
    Abstract
    Corresponding author: Antje Prasse (prasse.antje@mh-hannover.de)

    Sarcoidosis manifests with inflammatory granulomas in multiple organs, most commonly the lungs and lymph nodes. The diverse range of organ manifestations and the variety of disease-modifying factors such as environmental, genetic and patient-related factors all add to the clinical heterogeneity of the disease and make it difficult to find the best pharmacological treatment. Every patient appears to be different, and an individualized therapy is required. Immunosuppressive therapy is the cornerstone of the management of sarcoidosis. Current treatment options focus on suppressing immune responses by inhibiting macrophages, T-cells and cytokine signalling. Our knowledge of the pathogenesis of this heterogeneous disease has improved, and new drugs are currently being tested in clinical trials. This chapter reviews the current approaches to pharmacological treatment of sarcoidosis and highlights potential new drugs.

    Cite as: Caliskan C, Prasse A. Treating sarcoidosis and potential new drugs. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 328–336 [https://doi.org/10.1183/2312508X.10033620].

  26. Page 337
    Abstract
    Corresponding author: Surinder S. Birring (surinder.birring@nhs.net)

    Sarcoidosis is a heterogeneous disease with numerous clinically relevant end-points. Quality-of-life assessment is an increasingly used end-point in sarcoidosis that evaluates the impact of the condition from the patient's perspective. Quality-of-life assessment incorporates the sarcoidosis patient directly into the management of the disease through an emphasis on patient-centred care and shared decision making. Sarcoidosis-specific quality-of-life assessment tools have been designed, studied and validated, and their minimal clinically importance difference established. However, further research is needed with respect to this novel approach to assist with sarcoidosis management decisions.

    Cite as: Tully T, Judson MA, Patel AS, et al. Quality-of-life assessment. In: Bonella F, Culver DA, Israël-Biet D, eds. Sarcoidosis (ERS Monograph). Sheffield, European Respiratory Society, 2022; pp. 337–349 [https://doi.org/10.1183/2312508X.10033720].