Pulmonale Sarkoidose

ZUSAMMENFASSUNG

Sarkoidose ist eine seltene, granulomatöse Erkrankung unklarer Ätiologie, die vor allem das lymphatische System und die Lunge befällt, jedoch auch alle anderen Organe betreffen kann. Die Diagnose wird anhand passender klinischer Symptome, dem histologischen Nachweis von nicht nekrotisierenden Granulomen sowie dem Ausschluss relevanter Differenzialdiagnosen gestellt. Der histologische Nachweis von Granulomen gelingt häufig mittels endobronchialer ultraschallgesteuerter transbronchialer Feinnadelbiopsie der thorakalen Lymphknoten, alternativ können bronchoskopisch Schleimhaut- oder transbronchiale Parenchymbiopsien zur Diagnose vorgenommen werden. Die Entscheidung für eine immunsuppressive Therapie sollte vor allem unter Berücksichtigung der Nebenwirkungen dann getroffen werden, wenn die Sarkoidose die Lebensqualität der*s Betroffenen reduziert oder Organfunktionen einschränkt. Die Therapie erfolgt primär mit Kortikosteroiden und kann in der Zweitlinientherapie um Azathioprin oder Methotrexat (oder andere DMARD) als steroidsparende Medikamente erweitert werden. Die klinische Verlaufskontrolle zielt auf das Monitoring der Organfunktionen (z. B. Lungenfunktion) und der Lebensqualität.

Schlüsselwörter

Granulomatöse Erkrankungen - gemischte Ventilationsstörung - Bronchoskopie - immunsuppressive Therapie

Publication History

Article published online:
08 October 2024

• Literatur

• 1 Gribbin J, Hubbard RB, Jeune IL. et al Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax 2006; 61: 980
• 2 Fischer A, Zissel G, Nebel A. et al Genetisches Risikoprofil der Sarkoidose. Der Internist 2014; 55: 135-140
• 3 Arkema EV, Grunewald J, Kullberg S. et al Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden. Eur Respir J 2016; 48: 1690-1699
• 4 Arkema EV, Cozier YC. Sarcoidosis epidemiology: recent estimates of incidence, prevalence and risk factors. Curr Opin Pulm Med 2020; 26: 527-534
• 5 Ungprasert P, Carmona EM, Utz JP. et al Epidemiology of Sarcoidosis 1946–2013: A Population-Based Study. Mayo Clin Proc 2016; 91: 183-188
• 6 Grunewald J, Grutters JC, Arkema EV. et al Sarcoidosis. Nature Reviews Disease Primers 2019; 5: 45
• 7 Iannuzzi MC, Rybicki BA, Teirstein AS, Sarcoidosis N. Engl J Med 2007; 357: 2153-2165
• 8 Drent M, Crouser ED, Grunewald J. Challenges of Sarcoidosis and Its Management. N Engl J Med 2021; 385: 1018-1032
• 9 Fischer A, Grunewald J, Spagnolo P. et al Genetics of sarcoidosis. Semin Respir Crit Care Med 2014; 35: 296-306
• 10 Freitag-Wolf S, Schupp JC, Frye BC. et al Genetic and geographic influence on phenotypic variation in European sarcoidosis patients. Front Med (Lausanne) 2023; 10: 1218106
• 11 Newman LS, Rose CS, Bresnitz EA. et al A case control etiologic study of sarcoidosis: environmental and occupational risk factors. Am J Respir Crit Care Med 2004; 170: 1324-1330
• 12 Eishi Y. Etiologic link between sarcoidosis and Propionibacterium acnes. Respiratory Investigation 2013; 51: 56-68 https://doi.org/10.1016/j.resinv.2013.01.001
• 13 Baughman RP, Teirstein AS, Judson MA. et al Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001; 164: 1885-1889
• 14 Schupp JC, Freitag-Wolf S, Bargagli E. et al Phenotypes of organ involvement in sarcoidosis. European Respiratory Journal 2018; 51: 1700991
• 15 Judson MA. The Clinical Features of Sarcoidosis: A Comprehensive Review. Clin Rev Allergy Immunol 2015; 49: 63-78
• 16 Skowasch D, Gaertner F, Marx N. et al Diagnostik und Therapie der kardialen Sarkoidose. Der Kardiologe 2020; 14: 14-25
• 17 Bailey GL, Wells AU, Desai SR. Imaging of Pulmonary Sarcoidosis-A Review. J Clin Med 2024; 13
• 18 Nakatsu M, Hatabu H, Morikawa K. et al Large coalescent parenchymal nodules in pulmonary sarcoidosis: “sarcoid galaxy” sign. AJR Am J Roentgenol 2002; 178: 1389-1393
• 19 Drent M, Vries JD, Lenters M. et al Sarcoidosis: assessment of disease severity using HRCT. European Radiology 2003; 13: 2462-2471
• 20 Kim Y, Lee KS, Yoo JH. et al Radiologic Findings of Pulmonary Sarcoidosis: Comparison Between Radiograph and HRCT. jkrs 2016; 39: 73-80 https://doi.org/10.3348/jkrs.1998.39.1.73
• 21 Desai SR, Sivarasan N, Johannson KA. et al High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study. The Lancet Respiratory Medicine 2024; 12: 409-418
• 22 Régis C, Benali K, Rouzet F. FDG PET/CT Imaging of Sarcoidosis. Seminars in Nuclear Medicine 2023; 53: 258-272 https://doi.org/10.1053/j.semnuclmed.2022.08.004
• 23 Corte TJ, Wells AU, Nicholson AG. et al Pulmonary hypertension in sarcoidosis: A review. Respirology 2011; 16: 69-77 https://doi.org/10.1111/j.1440-1843.2010.01872.x
• 24 Kouranos V, Ward S, Kokosi MA. et al Mixed Ventilatory Defects in Pulmonary Sarcoidosis: Prevalence and Clinical Features. Chest 2020; 158: 2007-2014
• 25 Davies CWH, Tasker AD, Padley SPG. et al Air Trapping in Sarcoidosis on Computed Tomography: Correlation with Lung Function. Clinical Radiology 2000; 55: 217-221
• 26 Chambellan A, Turbie P, Nunes H. et al Endoluminal Stenosis of Proximal Bronchi in Sarcoidosis: Bronchoscopy, Function, and Evolution. CHEST 2005; 127: 472-481
• 27 Naccache J-M, Lavolé A, Nunes H. et al High-Resolution Computed Tomographic Imaging of Airways in Sarcoidosis Patients With Airflow Obstruction. Journal of Computer Assisted Tomography 2008; 32: 905-912
• 28 Hansell DM, Milne DG, Wilsher ML. et al Pulmonary sarcoidosis: morphologic associations of airflow obstruction at thin-section CT. Radiology 1998; 209: 697-704
• 29 Obi ON, Baughman RP. Mixed Obstructive and Restrictive Ventilatory Defect in Sarcoidosis: A New Phenotype?. CHEST 2020; 158: 1816-1817
• 30 Crouser ED, Maier LA, Wilson KC. et al Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. American Journal of Respiratory and Critical Care Medicine 2020; 201: e26-e51
• 31 Spagnolo P, Rossi G, Trisolini R. et al Pulmonary sarcoidosis. Lancet Respir Med 2018; 6: 389-402
• 32 Hu L-X, Chen R-X, Huang H. et al Endobronchial Ultrasound-guided Transbronchial Needle Aspiration versus Standard Bronchoscopic Modalities for Diagnosis of Sarcoidosis: A Meta-analysis. Chinese Medical Journal 2016; 129: 1607-1615
• 33 von Bartheld MB, Dekkers OM, Szlubowski A. et al Endosonography vs Conventional Bronchoscopy for the Diagnosis of Sarcoidosis: The GRANULOMA Randomized Clinical Trial. Jama 2013; 309: 2457-2464
• 34 Raghu G, Remy-Jardin M, Richeldi L. et al Idiopathic Pulmonary Fibrosis (an Update) and Progressive Pulmonary Fibrosis in Adults: An Official ATS/ERS/JRS/ALAT Clinical Practice Guideline. American Journal of Respiratory and Critical Care Medicine 2022; 205: e18-e47
• 35 Häntschel M, Eberhardt R, Petermann C. et al Diagnostic Yield of Transbronchial Lung Cryobiopsy Compared to Transbronchial Forceps Biopsy in Patients with Sarcoidosis in a Prospective, Randomized, Multicentre Cross-Over Trial. Journal of Clinical Medicine 2021; 10: 5686
• 36 Terschluse C, Feineis M, Meschede W. et al Bronchoscopy in sarcoidosis – EBUS-TBNA, transbronchial biopsy or cryobiopsy?. European Respiratory Journal 2022; 60: 2278
• 37 Polychronopoulos VS, Prakash UBS. Airway Involvement in Sarcoidosis. Chest 2009; 136: 1371-1380 https://doi.org/10.1378/chest.08-2569
• 38 Welker L, Jörres RA, Costabel U. et al Predictive value of BAL cell differentials in the diagnosis of interstitial lung diseases. European Respiratory Journal 2004; 24: 1000-1006
• 39 Kantrow S, Meyer K, Kidd P. et al The CD4/CD8 ratio in BAL fluid is highly variable in sarcoidosis. European Respiratory Journal 1997; 10: 2716-2721
• 40 Verstraeten A, Demedts M, Verxvilghen J. et al Predictive Value of Bronchoalveolar Lavage in Pulmonary Sarcoidosis. CHEST 1990; 98: 560-567
• 41 Laviolette M, Forge JL, Tennina S. et al Prognostic Value of Bronchoalveolar Lavage Lymphocyte Count in Recently Diagnosed Pulmonary Sarcoidosis. CHEST 1991; 100: 380-384
• 42 Drent M, Jacobs J, Vries Jd. et al Does the cellular bronchoalveolar lavage fluid profile reflect the severity of sarcoidosis?. European Respiratory Journal 1999; 13: 1338-1344
• 43 Ziegenhagen MW, Rothe ME, Schlaak M. et al Bronchoalveolar and serological parameters reflecting the severity of sarcoidosis. European Respiratory Journal 2003; 21: 407-413
• 44 Chrétien J, Venet A, Danel C. et al Bronchoalveolar Lavage in Sarcoidosis. Respiration 2009; 48: 222-230
• 45 Cohen Aubart F, Lhote R, Amoura A. et al Drug-induced sarcoidosis: an overview of the WHO pharmacovigilance database. J Intern Med 2020; 288: 356-362
• 46 Judson MA, Gilbert GE, Rodgers JK. et al The utility of the chest radiograph in diagnosing exacerbations of pulmonary sarcoidosis. Respirology 2008; 13: 97-102 https://doi.org/10.1111/j.1440-1843.2007.01206.x
• 47 Zappala CJ, Desai SR, Copley SJ. et al Accuracy of Individual Variables in the Monitoring of Long-term Change in Pulmonary Sarcoidosis as Judged by Serial High-Resolution CT Scan Data. CHEST 2014; 145: 101-107 10378/chest.12-2479
• 48 Vorselaars AD, van Moorsel CH, Zanen P. et al ACE and sIL-2R correlate with lung function improvement in sarcoidosis during methotrexate therapy. Respir Med 2015; 109: 279-285
• 49 Rigat B, Hubert C, Alhenc-Gelas F. et al An insertion/deletion polymorphism in the angiotensin I-converting enzyme gene accounting for half the variance of serum enzyme levels. J Clin Invest 1990; 86: 1343-1346
• 50 Krasowski MD, Savage J, Ehlers A. et al Ordering of the Serum Angiotensin-Converting Enzyme Test in Patients Receiving Angiotensin-Converting Enzyme Inhibitor Therapy: An Avoidable but Common Error. Chest 2015; 148: 1447-1453
• 51 Ziegenhagen MW, Benner UK, Zissel G. et al Sarcoidosis: TNF-alpha release from alveolar macrophages and serum level of sIL-2R are prognostic markers. Am J Respir Crit Care Med 1997; 156: 1586-1592
• 52 Grutters JC, Fellrath J-M, Mulder L. et al Serum soluble interleukin-2 receptor measurement in patients with sarcoidosis: a clinical evaluation. Chest 2003; 124: 186-195
• 53 Schimmelpennink MC, Quanjel M, Vorselaars A. et al Value of serum soluble interleukin-2 receptor as a diagnostic and predictive biomarker in sarcoidosis. Expert Rev Respir Med 2020; 14: 749-756
• 54 Prasse A, Katic C, Germann M. et al Phenotyping sarcoidosis from a pulmonary perspective. Am J Respir Crit Care Med 2008; 177: 330-336
• 55 Mañá J, Rubio-Rivas M, Villalba N. et al Multidisciplinary approach and long-term follow-up in a series of 640 consecutive patients with sarcoidosis: Cohort study of a 40-year clinical experience at a tertiary referral center in Barcelona, Spain. Medicine (Baltimore) 2017; 96: e7595
• 56 Baughman RP, Judson MA, Wells A. The indications for the treatment of sarcoidosis: Wells Law. Sarcoidosis Vasc Diffuse Lung Dis 2017; 34: 280-282
• 57 Gibson GJ, Prescott RJ, Muers MF. et al British Thoracic Society Sarcoidosis study: effects of long term corticosteroid treatment. Thorax 1996; 51: 238-247
• 58 Pietinalho A, Tukiainen P, Haahtela T. et al Oral prednisolone followed by inhaled budesonide in newly diagnosed pulmonary sarcoidosis: a double-blind, placebo-controlled multicenter study. Finnish Pulmonary Sarcoidosis Study Group. Chest 1999; 116: 424-431
• 59 Baughman RP, Valeyre D, Korsten P. et al ERS clinical practice guidelines on treatment of sarcoidosis. Eur Respir J 2021; 58
• 60 Valeyre D, Prasse A, Nunes H. et al Sarcoidosis. Lancet (London, England). 2014; 383: 1155-1167
• 61 Broos CE, Poell LHC, Looman CWN. et al No evidence found for an association between prednisone dose and FVC change in newly-treated pulmonary sarcoidosis. Respir Med 2018; 138s: S31-S37
• 62 Dhooria S, Sehgal IS, Agarwal R. et al High-dose (40 mg) versus low-dose (20 mg) prednisolone for treating sarcoidosis: a randomised trial (SARCORT trial). Eur Respir J 2023; 62
• 63 Baughman RP, Winget DB, Lower EE. Methotrexate is steroid sparing in acute sarcoidosis: results of a double blind, randomized trial. Sarcoidosis Vasc Diffuse Lung Dis 2000; 17: 60-66
• 64 Fang C, Zhang Q, Wang N. et al Effectiveness and tolerability of methotrexate in pulmonary sarcoidosis: A single center real-world study. Sarcoidosis Vasc Diffuse Lung Dis 2019; 36: 217-227
• 65 Vorselaars ADM, Wuyts WA, Vorselaars VMM. et al Methotrexate vs azathioprine in second-line therapy of sarcoidosis. Chest 2013; 144: 805-812
• 66 Baughman RP, Lower EE. Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2004; 21: 43-48
• 67 Papiris S, Stagaki E, Papadaki G. et al Mycophenolate mofetil as an alternative treatment in sarcoidosis. Pulm Pharmacol Ther 2019; 58: 101840
• 68 Baughman RP, Drent M, Kavuru M. et al Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J Respir Crit Care Med 2006; 174: 795-802
• 69 Baughman RP, Grutters JC. New treatment strategies for pulmonary sarcoidosis: antimetabolites, biological drugs, and other treatment approaches. Lancet Respir Med 2015; 3: 813-822
• 70 Majjad A, Bezza A, Biyi A. et al Pulmonary Sarcoidosis following Etanercept Treatment for Ankylosing Spondylitis: A Case Report and Review of the Literature. Case Rep Rheumatol 2018; 2018: 9867248
• 71 Soriano D, Müller-Quernheim J, Frye BC. Sarkoidose. Der Pneumologe 2020; 17: 65-80
• 72 Obi ON, Lower EE, Baughman RP. Biologic and advanced immunomodulating therapeutic options for sarcoidosis: a clinical update. Expert Rev Clin Pharmacol 2021; 14: 179-210
• 73 Damsky W, Wang A, Kim DJ. et al Inhibition of type 1 immunity with tofacitinib is associated with marked improvement in longstanding sarcoidosis. Nat Commun 2022; 13: 3140
• 74 Obi ON, Saketkoo LA, Russell AM. et al Sarcoidosis: Updates on therapeutic drug trials and novel treatment approaches. Front Med (Lausanne) 2022; 9: 991783
• 75 Nakamizo S, Kabashima K. Metabolic reprogramming and macrophage polarization in granuloma formation. Int Immunol 2024;
• 76 Barnett CF, Bonura EJ, Nathan SD. et al Treatment of sarcoidosis-associated pulmonary hypertension. A two-center experience. Chest 2009; 135: 1455-1461
• 77 Baughman RP, Culver DA, Cordova FC. et al Bosentan for sarcoidosis-associated pulmonary hypertension: a double-blind placebo controlled randomized trial. Chest 2014; 145: 810-817
• 78 Le Pavec J, Valeyre D, Gazengel P. et al Lung transplantation for sarcoidosis: outcome and prognostic factors. Eur Respir J 2021; (58)
• 79 Vis R, van de Garde EMW, Grutters JC. et al The effects of pharmacological interventions on quality of life and fatigue in sarcoidosis: a systematic review. European Respiratory Review 2020; 29: 190057
• 80 Alsina-Restoy X, Torres-Castro R, Caballería E. et al Pulmonary rehabilitation in sarcoidosis: A systematic review and meta-analysis. Respir Med 2023; 219: 107432