In Morning Report on May 10, 2022 we discussed a case of sarcoidosis. A recap of the key points and some high-yield references are included below.
1. Clinical Syndromes of Sarcoidosis
Sarcoidosis is an idiopathic non-infectious granulomatous multi-system disease with lung involvement 90% of the time. On histopathology, sarcoidosis will reveal non-caseating granulomas.
There can be an array of symptoms including patients having sarcoidosis being asymptomatic or can present with cough, dyspnea, fever, arthralgias, malaise, erythema nodosum, chest pain, among other symptoms. Central nervous system, cardiac and ocular sarcoid
There are two acute sarcoid syndromes to know of:
- Lofgren’s syndrome: erythema nodosum, bilateral hilar adenopathy, and arthralgias (can include fever)
- Heerfordt-Waldenstrom syndrome: parotid enlargement, anterior uveitis, facial nerve palsy, fever
2. Staging of Pulmonary Sarcoidosis
The staging of pulmonary sarcoidosis is included below. 85% of stage I pulmonary sarcoid resolves spontaneously, while 50% of stage II resolves spontaneously. Steroids can be used for symptoms and methotrexate/other immunosuppressives are occasionally used
|Stage 1||Bilateral hilar lymphadenopathy ± right paratracheal lymphadenopathy|
|Stage 2||Bilateral hilar lymphadenopathy and diffuse interstitial disease|
|Stage 3||Interstitial disease only (reticulonodular pattern or nodular pattern)|
|Stage 4||Pulmonary fibrosis (honeycombing)|
The American Thoracics Society guidelines (referenced below) make some key points regarding sarcoidosis diagnosis and investigations. These include:
- If there is a high suspicion for sarcoidosis, one does not need to sample lymph nodes (do close clinical follow up)
- For patients presenting with asymptomatic, bilateral hilar lymphadenopathy, there are no recommendations for or against lymph node sampling. If not sampled, need close follow up
- If a patient has suspected sarcoidosis and mediastinal or hilar adenopathy and will be obtaining tissue sample, endobronchial ultrasound (EBUS) is the recommended initial modality for lymph node sampling
- If patients with sarcoidosis do not have ocular symptoms, baseline eye examination to screen for ocular sarcoidosis is recommended
- For patients with sarcoidosis who do not have renal sarcoid or symptoms of this, serum creatinine for screening is recommended
- Similarly, if there is no established hepatic symptoms or hepatic sarcoidosis, baseline serum ALP is suggested for screening (there are no recommendations for or against transaminase testing)
- If patients do not have signs or symptoms of hypercalcemia, baseline serum calcium testing is recommended to screen. If vitamin D replacement is indicated in a patient with sarcoid or a need for testing is required, it is suggested that both 25OH vitamin D and 1,25OH vitamin D are tested for
- Baseline CBC is suggested to screen for heme abnormalities
- Baseline ECG to screen for cardiac involvement in patients with extracardiac sarcoid who do not have cardiac symptoms (not recommended to have TTE or 24-hour Holter in patients who do not have cardiac signs or symptoms)
4. Management of Sarcoidosis
The European Respiratory Society clinical practice guidelines on treatment of sarcoidosis are referenced below as well as a nice review from NEJM from 2007.
As it relates to pulmonary sarcoidosis, those who at higher risk of mortality/morbidity, glucocorticoids are recommended to improve/preserve FVC (forced vital capacity) and quality of life. If patients are symptomatic and higher risk and continue to have unacceptable disease symptoms or side effects, methotrexate is suggested as add-on therapy. If still refractory from this, infliximab should be added.
Pulmonary rehabilitation is recommended for fatigue related to sarcoidosis.
Erythema nodosum usually treated with NSAIDs. If a patient does not respond to first-line treatment with NSAIDs, then prednisone can be prescribed. 80% of patients with Lofgren’s syndrome have a monophasic illness and very good prognosis.
Cutaneous sarcoidosis and cosmetically relevant active skin lesions that are not under control with local treatment, oral steroids can be considered. If glucorticoids or other immunosuppressives are not effective, infliximab can be used.
Neurosarcoid is also treated with steroids +/- other immunosuppressives such as methotrexate. Ocular disease, hypercalcemia, and symptomatic liver disease also warrant treatment.
5. A Word on Cardiac Sarcoidosis
Cardiac sarcoidosis is more common than previously reported. Patients who have functional cardiac abnormalities, including heart block, dysrhythmias or cardiomyopathy, glucocorticoids +/- other immunosuppressives are recommended.
Interestingly, Birnie et al. in 2016 published in ACC (first reference below) highlighting expert consensus recommendations for diagnosing cardiac sarcoidosis. One pathway is through myocardial biopsy but another pathway is if there is extra-cardiac sarcoid already confirmed on histology and other causes of cardiac manifestations are excluded and the patient has one of the following, a diagnosis can be made:
- Steroid and/or immunosuppressant-responsive cardiomyopathy or heart block
- Unexplained EF less than 40$%
- Unexplained sustained ventricular tachycardia (spontaneous or induced)
- Mobitz type II second- or third-degree heart block
- Patchy uptake on dedicated cardiac FDG-PET (in a pattern consistent with CS)
- LGE on CMR (in a pattern consistent with CS)
- Positive gallium uptake (in a pattern consistent with CS)
Read more in the paper that is referenced below (first reference).
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- Birnie, D. H., Nery, P. B., Ha, A. C., & Beanlands, R. S. (2016). Cardiac Sarcoidosis. Journal of the American College of Cardiology, 68(4), 411–421. https://doi-org.myaccess.library.utoronto.ca/10.1016/j.jacc.2016.03.605
- Chauhan A, Jandial A, Mishra K, et al. Acute arthritis, skin rash and Lofgren’s syndrome. BMJ Case Reports CP 2021;14:e239239. Reference: https://casereports.bmj.com/content/14/6/e239239
- Crouser, E. D., Maier, L. A., Wilson, K. C., Bonham, C. A., Morgenthau, A. S., Patterson, K. C., Abston, E., Bernstein, R. C., Blankstein, R., Chen, E. S., Culver, D. A., Drake, W., Drent, M., Gerke, A. K., Ghobrial, M., Govender, P., Hamzeh, N., James, W. E., Judson, M. A., Kellermeyer, L., … Baughman, R. P. (2020). Diagnosis and Detection of Sarcoidosis. An Official American Thoracic Society Clinical Practice Guideline. American journal of respiratory and critical care medicine, 201(8), e26–e51. https://doi.org/10.1164/rccm.202002-0251ST – https://www.atsjournals.org/doi/10.1164/rccm.202002-0251ST
- Robert P. Baughman, Dominique Valeyre, Peter Korsten, Alexander G. Mathioudakis, Wim A. Wuyts, Athol Wells, Paola Rottoli, Hiliaro Nunes, Elyse E. Lower, Marc A. Judson, Dominique Israel-Biet, Jan C. Grutters, Marjolein Drent, Daniel A. Culver, Francesco Bonella, Katerina Antoniou, Filippo Martone, Bernd Quadder, Ginger Spitzer, Blin Nagavci, Thomy Tonia, David Rigau, Daniel R. Ouellette. European Respiratory Journal Dec 2021, 58 (6) 2004079; DOI: 10.1183/13993003.04079-2020 – https://erj.ersjournals.com/content/erj/58/6/2004079.full.pdf
- Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med. 2007 Nov 22;357(21):2153-65. doi: 10.1056/NEJMra071714. PMID: 18032765.
- Saltman, A. P., & Kuriya, B. (2017). Löfgren syndrome in acute sarcoidosis. CMAJ : Canadian Medical Association journal = journal de l’Association medicale canadienne, 189(39), E1230. https://doi-org.myaccess.library.utoronto.ca/10.1503/cmaj.170547 – https://www.cmaj.ca/content/189/39/E1230