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Sarcoidosis Treatment & Management

  • Author: Nader Kamangar, MD, FACP, FCCP, FCCM; Chief Editor: Zab Mosenifar, MD, FACP, FCCP  more...
 
Updated: May 31, 2016
 

Medical Care

Most patients (>75%) require only symptomatic therapy with NSAIDs. Approximately 10% of patients need treatment for extrapulmonary disease, while 15% of patients require treatment for persistent pulmonary disease.

Steroid treatment

Corticosteroids are the mainstay of therapy.

Generally, prednisone given daily and then tapered over a 6-month course is adequate for pulmonary disease. Earlier recommendations suggested an initial dose of 1 mg/kg/d of prednisone; however, more recent expert opinions endorse a lower dose (eg, 40 mg/d), which is tapered to every-other-day long-term therapy over several weeks. In one study, treatment of acute exacerbations of pulmonary sarcoidosis with steroid doses as low as 20 mg of prednisone for a median of 21 days improved spirometry back to baseline and improved clinical symptoms.[55] Most patients who require long-term steroids can be treated using 10-15 mg of prednisone every other day.

Some data suggest that corticosteroid use may be associated with increased relapse rates. However, data suggest early treatment of stage II sarcoidosis with oral prednisolone for 3 months followed by inhaled budesonide for 15 months improves 5-year pulmonary function and reduces the need for future steroid treatment.[56]

High-dose inhaled corticosteroids may be an option, but conclusive data are lacking. Inhaled corticosteroids, in particular, can be used in patients with endobronchial disease.

Although corticosteroids are used for symptom relief and remain the mainstay of therapy, their efficacy in this disease is unclear. Since many patients' conditions improve spontaneously, showing a true benefit to therapy requires a careful control arm.

The best study addressing corticosteroids was the recently completed multicenter trial from Britain sponsored by the British Thoracic Society. In this nonrandomized study, 55 patients were selectively observed or treated with corticosteroids. Additionally, patients who were thought to have an immediate indication for steroids were treated. The trial required a 6-month run-in period to exclude patients who improved spontaneously. At the end of the trial, the groups treated with long-term steroids fared better on some measures than did the patients who were observed and treated with short bursts of steroids (see Table 1 below for detail).

Acthar gel (repository corticotropin injection) was used to treat pulmonary sarcoidosis in the 1950s. It was abandoned because of cost and toxicity compared with prednisone. More recently, it has been suggested as an alternative in patients who are on high-dose prednisone.[57]

Table 2. Results of Multicenter Trial Sponsored by the British Thoracic Society (Open Table in a new window)

Characteristics Group La Group Sb P
Dyspnea score (range 1-4) 0.24 0.47 NS
Fibrosis score (range 0-16) 0.83 1.47 NS
FEV1c (% predicted) 95.9 86.9 0.05
VCd (% predicted) 99.8 90.8 0.02
DLCOe (% predicted) 84.3 77.7 NS
Weight gain (kg) +3.26 +0.99 0.02
a Long-term steroids.



b Short bursts of steroids.



c Forced expiratory volume in 1 second.



d Ventilatory capacity.



e Diffusing capacity of lung for carbon monoxide.



 

Nonsteroid treatment

Noncorticosteroid agents are being increasingly tried. Common indications for the initiation of such agents include steroid-resistant disease, intolerable adverse effects, or patient desire not to take corticosteroids.

Methotrexate (MTX) has been a successful alternative to prednisone and is a steroid-sparing agent.[58]

Chloroquine and hydroxychloroquine are antimalarial drugs with immunomodulating properties, which have been used for cutaneous lesions, hypercalcemia, neurological sarcoidosis, and bone lesions. Chloroquine has also been shown to be efficacious for the treatment and maintenance of chronic pulmonary sarcoidosis.[3, 4]

Cyclophosphamide has been rarely used with modest success as a steroid-sparing treatment in patients with refractory sarcoidosis.[5, 6]

Azathioprine is another second-line therapy, which is best used as a steroid-sparing agent rather than as a single-drug treatment for sarcoidosis.[7]

Chlorambucil is an alkylating agent that may be beneficial in patients with progressive disease unresponsive to corticosteroids.[8]

Cyclosporine is a fungal cyclic polypeptide with lymphocyte-suppressive properties and may be of limited benefit in skin sarcoidosis or in progressive sarcoidosis resistant to conventional therapy.[9]

Infliximab[10, 11] and thalidomide[12, 13] have also been used for refractory sarcoidosis, particularly for cutaneous disease. Infliximab appears to be an effective treatment for patients with systemic manifestations such as lupus pernio, uveitis, hepatic sarcoidosis, and neurosarcoidosis.

In addition, long-term treatment with infliximab can be effective for extrapulmonary sarcoidosis, according to a retrospective study of 26 patients with biopsy-proven sarcoidosis.[14] In the study, sustained resolution or improvement occurred in 58.5% of organs, but disease activity progressed in 5.7% despite treatment. In 57.7% of patients, there were adverse events during an average duration of therapy of 46.2 months.[14] Improvement in pulmonary imaging findings was observed in patients with pulmonary sarcoid after initiation of infliximab treatment, but results at post-treatment were inconclusive. Infliximab treatment was well tolerated.[14]

Callejas-Rubio et al reported inconsistent results with tumor necrosis factor (TNF)–inhibitor therapy.[59] However, at least one study has shown treatment with adalimumab can reduce disease activity, as assessed by fluorodeoxyglucose positron emission tomography (FDG-PET) scanning.[60] Adalimumab has also been used successfully in sarcoidosis patients with refractory chronic noninfectious uveitis.[61]

Nontreatment and other issues

For pulmonary disease, asymptomatic pulmonary function testing and/or chest radiography abnormalities are not an indication for treatment. In patients with minimal symptoms, serial reevaluation is prudent. Significant respiratory symptoms associated with pulmonary function test and chest radiograph abnormalities likely require therapy. For such patients, treatment is indicated if objective evidence of recent deterioration in lung function exists. As mentioned above, corticosteroids can result in improvements in the functional vital capacity and in the radiographic appearance in patients with more severe stage II and III disease.

One study demonstrated an approach that may minimize the use of corticosteroids without harming the patient. This is accomplished by withholding therapy unless the patient shows at least a 15% decline in one spirometric measure associated with increasing symptoms or, if asymptomatic, withholding therapy unless the patient shows worsening pulmonary function test results and a change in the chest radiograph.

For extrapulmonary sarcoidosis involving such critical organs as the heart, liver, eyes, kidneys, or central nervous system, medical intervention is indicated.

Topical corticosteroids are effective for ocular disease.

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Surgical Care

Lung transplantation is a viable option for patients with stage IV sarcoidosis. Transplantation in such patients should be strongly considered when the forced vital capacity falls below 50% predicted and/or the forced expiratory volume in 1 second falls below 40% predicted.[15] Patients with advanced sarcoidosis awaiting lung transplantation have a high mortality rate with a median survival of less than 2 years. Mortality is most closely linked to elevated right atrial pressure. In one retrospective cohort study, survival after transplantation determined by the Kaplan-Meier method was 62% at both 1 and 2 years, and a mere 50% at 3 years.[62]

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Complications

Sarcoidosis may initially manifest or be reactivated during or shortly after treatment with antiviral therapy in patients with chronic hepatitis C viral infection.[63]

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Long-Term Monitoring

Monitor pulmonary function and chest radiography every 6-12 months.

Assess for progression or resolution.

Determine if previously uninvolved organs have become affected.

Annual slit-lamp eye examination and ECG are recommended.

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Contributor Information and Disclosures
Author

Nader Kamangar, MD, FACP, FCCP, FCCM Professor of Clinical Medicine, University of California, Los Angeles, David Geffen School of Medicine; Chief, Division of Pulmonary and Critical Care Medicine, Vice-Chair, Department of Medicine, Olive View-UCLA Medical Center

Nader Kamangar, MD, FACP, FCCP, FCCM is a member of the following medical societies: Academy of Persian Physicians, American Academy of Sleep Medicine, American Association for Bronchology and Interventional Pulmonology, American College of Chest Physicians, American College of Critical Care Medicine, American College of Physicians, American Lung Association, American Medical Association, American Thoracic Society, Association of Pulmonary and Critical Care Medicine Program Directors, Association of Specialty Professors, California Sleep Society, California Thoracic Society, Clerkship Directors in Internal Medicine, Society of Critical Care Medicine, Trudeau Society of Los Angeles, World Association for Bronchology and Interventional Pulmonology

Disclosure: Nothing to disclose.

Coauthor(s)

Andrew F Shorr, MD, MPH Associate Professor of Medicine, Georgetown University School of Medicine, Associate Direfctor of Pulmonary and Critical Care, Washington Hospital Center

Andrew F Shorr, MD, MPH is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Thoracic Society

Disclosure: Nothing to disclose.

Payam Rohani, MD Resident Physician, Department of Internal Medicine, Olive View-UCLA Medical Center

Payam Rohani, MD is a member of the following medical societies: American College of Physicians

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Zab Mosenifar, MD, FACP, FCCP Geri and Richard Brawerman Chair in Pulmonary and Critical Care Medicine, Professor and Executive Vice Chairman, Department of Medicine, Medical Director, Women's Guild Lung Institute, Cedars Sinai Medical Center, University of California, Los Angeles, David Geffen School of Medicine

Zab Mosenifar, MD, FACP, FCCP is a member of the following medical societies: American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society

Disclosure: Nothing to disclose.

Additional Contributors

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP Thomas H Davis Chair in Pulmonary Medicine, Chief, Section on Pulmonary, Critical Care, Allergy and Immunologic Diseases, Professor of Internal Medicine, Pediatrics, and Translational Science, Associate Director, Center for Genomics and Personalized Medicine Research, Wake Forest University School of Medicine; Executive Director of the Respiratory Service Line, Wake Forest Baptist Medical Center

Stephen P Peters, MD, PhD, FACP, FAAAAI, FCCP, FCPP is a member of the following medical societies: American Academy of Allergy Asthma and Immunology, American Association of Immunologists, American College of Chest Physicians, American College of Physicians, American Federation for Medical Research, American Thoracic Society, Sigma Xi

Disclosure: Serve(d) as a speaker or a member of a speakers bureau for: Integrity CE, Merck<br/>Received income in an amount equal to or greater than $250 from: – Array Biopharma, AstraZeneca, Aerocrine, Airsonett AB, Boehringer-Ingelheim, Experts in Asthma, Gilead, GlaxoSmithKline, Merck, Novartis, Ono Pharmaceuticals, Pfizer, PPD Development, Quintiles, Sunovion, Saatchi & Saatichi, Targacept, TEVA, Theron.

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Stage I sarcoidosis.
Stage II sarcoidosis.
Stage III sarcoidosis.
Table 1. Prognosis
Stage Remission (%) Asymptomatic at 5 y (%) Chest Radiograph Clearing (%) Mortality (%)
Stage I 60-90 95 54 0
Stage II 40-70 58 31 11
Stage III 10-20 25 10 18
Stage IV 0 N/A 0 N/A
Table 2. Results of Multicenter Trial Sponsored by the British Thoracic Society
Characteristics Group La Group Sb P
Dyspnea score (range 1-4) 0.24 0.47 NS
Fibrosis score (range 0-16) 0.83 1.47 NS
FEV1c (% predicted) 95.9 86.9 0.05
VCd (% predicted) 99.8 90.8 0.02
DLCOe (% predicted) 84.3 77.7 NS
Weight gain (kg) +3.26 +0.99 0.02
a Long-term steroids.



b Short bursts of steroids.



c Forced expiratory volume in 1 second.



d Ventilatory capacity.



e Diffusing capacity of lung for carbon monoxide.



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