• Users Online: 385
  • Print this page
  • Email this page

Table of Contents
Year : 2021  |  Volume : 23  |  Issue : 3  |  Page : 137-144

Update in treatment of pulmonary sarcoidosis

Department of Pulmonary Medicine, Faculty of Medicine, Hacettepe University, Ankara, Turkey

Date of Submission25-Nov-2020
Date of Decision06-Feb-2021
Date of Acceptance13-Feb-2021
Date of Web Publication01-Dec-2021

Correspondence Address:
Dr. Elif Babaoglu
Department of Pulmonary Medicine, Faculty of Medicine, Hacettepe University, Sihhiye, Ankara
Login to access the Email id

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/ejop.ejop_120_20

Rights and Permissions

Sarcoidosis is a chronic granulomatous multisystem disease with an unknown etiology. The diagnosis of sarcoidosis relies on the presence of noncaseating granuloma on histopathological examination with compatible clinical presentation and exclusion of other causes of granulomatous inflammation. Lungs and intrathoracic lymph nodes are the most commonly affected organs. Most of the patients are asymptomatic. Symptomatic patients generally have spontaneous resolution. 25% of patients have progressive lung disease and 10% of patients have organ failure. Corticosteroids, immunosuppressive, cytotoxic, and antimalarial drugs are used for sarcoidosis treatment. The decision of appropriate treatment is very important. The aim of this review is to summarize the actual treatment of pulmonary sarcoidosis.

Keywords: Corticosteroids, immunosuppressive agents, pulmonary sarcoidosis, treatment

How to cite this article:
Babaoglu E. Update in treatment of pulmonary sarcoidosis. Eurasian J Pulmonol 2021;23:137-44

How to cite this URL:
Babaoglu E. Update in treatment of pulmonary sarcoidosis. Eurasian J Pulmonol [serial online] 2021 [cited 2022 Jan 25];23:137-44. Available from: https://www.eurasianjpulmonol.com/text.asp?2021/23/3/137/331669

  Introduction Top

Sarcoidosis is a chronic granulomatous multisystem disease with an unknown etiology. It develops in genetically susceptible individuals with environmental, occupational, or infectious exposure.[1],[2]

Main pathological tissue infiltration is noncaseating granuloma. The diagnosis of sarcoidosis relies on the presence of noncaseating granuloma on histopathological examination with compatible clinical presentation and exclusion of other causes of granulomatous inflammation.[3],[4]

Managing patients with sarcoidosis is sometimes difficult for clinicians because of heterogeneous manifestations and relatively lack of enough data on treatment. Corticosteroids, immunosuppressive, cytotoxic, and antimalarial drugs are used for sarcoidosis treatment. The decision of appropriate treatment is very important. The aim of this review is to summarize the treatment of pulmonary sarcoidosis.

  Epidemiology Top

The incidence of sarcoidosis varies according to the ethnic groups. The highest incidence is observed among African-Americans (17–35 per 100,000 population) followed by Whites (5–12 per 100,000 population), while the lowest annual incidence is reported among Asians and Hispanics (1–3 per 100,000 population). Female-to-male prevalence ratio is 2:1. Sarcoidosis is a disease of middle-aged people, with the average age of 35–50 years.[5]

  Clinical Manifestations of Pulmonary Sarcoidosis Top

Lungs and intrathoracic lymph nodes are the most commonly affected organs in sarcoidosis (over 90% of patients).[5],[6],[7],[8],[9],[10],[11],[12] The clinical findings of pulmonary sarcoidosis are variable. It can change from asymptomatic condition to progressive life-threatening disease. Most of the patients are asymptomatic. In symptomatic patients, cough, dyspnea, or chest discomfort can be found. Symptomatic patients generally have spontaneous resolution. 25% of patients have progressive lung disease and 10% of patients have organ failure.[13],[14],[15]

Pulmonary sarcoidosis can be categorized into four stages according to the radiological features [Table 1]. The prognosis is less favorable with more advanced stages. Spontaneous regression is 80% in Stage I and chronic respiratory impairment is less than 5%. However, spontaneous regression of radiographic abnormalities is seen in only one-third of patients with Stage III disease, and chronic respiratory impairment is 5-fold increase in patients with Stage III and Stage IV diseases compared with Stage I disease.[16],[17],[18],[19]
Table 1: Stages of pulmonary sarcoidosis

Click here to view

  Diagnosis Top

Clinical and radiological findings are not enough for definitive diagnosis. Further, only presence of noncaseating granuloma on biopsy is not enough because of several other diseases that can cause similar histopathological changes. Compatible clinical, radiological, and histopathological findings with exclusion of other causes are needed for the definitive diagnosis. The only exceptions that we do not need histopathological diagnosis are:

  1. Löfgren syndrome (bilateral hilar adenopathy, erythema nodosum, fever, and arthritis)
  2. Heerfordt–Waldenström syndrome or uveoparotid fever (fever, parotid enlargement, facial palsy, and anterior uveitis)
  3. Asymptomatic bilateral hilar lymphadenopathy.

In these situations, a careful follow-up must be done to confirm the diagnosis.[20],[21] After the diagnosis of sarcoidosis, evaluation must be done for other comorbidities such as heart failure or pulmonary hypertension that can contribute to the symptoms but not respond to corticosteroid therapy.[22]

  Treatment of Pulmonary Sarcoidosis with Corticosteroids Top

Most of the sarcoidosis patients have asymptomatic or nonprogressive diseases that regress spontaneously. In progressive symptomatic disease, there is not any permanent cure. Corticosteroids are the most preferred drugs in sarcoidosis treatment. They used for relief of the symptoms and control of respiratory impairment, but they do not cure the disease. They attenuate the granulomatous inflammation and prevent the development of irreversible end-organ damage such as fibrotic lung disease and honeycombing. When we could not use corticosteroids because of toxicity or patient-related contraindications, we can use other agents [Table 2]. Indications, optimal duration of treatment, avoiding excess toxicity from medications, and monitorization of the response to therapy are the main points.
Table 2: Drugs used in pulmonary sarcoidosis treatment

Click here to view

First of all, we must decide to whom we should treat or observe. Sarcoidosis patients who do not need systemic therapy and can be followed are:

  1. Asymptomatic patients with Stage I disease: Most of them (60–80%) have spontaneous remission
  2. Asymptomatic patients with Stage II disease: In this group, patients have normal or mild obstructive or restrictive pulmonary function. We may give inhaled steroids to patients with obstructive pulmonary function test. However, before starting systemic corticosteroid therapy, we must observe them at least 3–6 months for progression of pulmonary function impairment or gas exchange. 50% of patients without progression will have spontaneous resolution by 36 months
  3. Asymptomatic patients with Stage III disease: We may give inhaled steroids to patients with obstructive pulmonary function test, and we must follow them for 3–6 months. 33% of patients without progression may have spontaneous resolution.[23]

    • Effect of inhaled steroids in sarcoidosis is conflicting. They modulate the alveolitis in sarcoidosis. Improvement in cough, dyspnea, and wheezing is seen by using inhaled steroids, but no improvement is seen in pulmonary functions.[24] Inhaled steroids doses for sarcoidosis are budesonide (800–1600 mcg twice daily) and fluticasone (500–1000 mcg twice daily). These drugs are advised at least for 4–8 weeks. Indications of inhaled steroids are:[25]

      • Mild pulmonary symptoms (cough or dyspnea) or abnormal pulmonary functions in Stage I or II disease
      • Instead of long-term low-dose (5–10 mg daily) prednisone[24],[25]

During follow-up, if patients have the combination of these finding below, we should start systemic therapy:

  • Severe pulmonary symptoms (dyspnea, cough, and chest tightness)
  • Progressive pulmonary function abnormalities:

    • ≥4 decrease in oxygen saturation at rest or exercise or
    • ≥15% decrease in forced vital capacity (FVC) or
    • ≥10% decrease in total lung capacity (TLC) or
    • ≥20% decrease in diffusing lung capacity (DLCO).

  • Worsening radiographic changes.[15],[26],[17]

In clinically severe disease, we should start systemic corticosteroid therapy without waiting. These patients generally have combination of:

  • Severe pulmonary symptoms (dyspnea, cough, and chest tightness)
  • Abnormal pulmonary functions:

    • FEV1 and FVC <70% and/or
    • DLCO <60% and/or
    • Oxygen saturation ≤90

  • Diffuse radiographic opacities.[15],[26],[27]

Before starting corticosteroids, patients must be evaluated for latent tuberculosis and hepatitis B. If needed, prophylactic drugs must be started for them.

The initial sarcoidosis therapy dose for oral prednisone is 20–40 mg/day (0.3–0.6 mg/kg ideal body weight). If the clinical findings are not severe and the disease is slowly progressive, 20 mg/day oral prednisone will be appropriate. Otherwise, 40 mg/day oral prednisone must be preferred.[28]

Initial therapy must be continued for 4–8 weeks. Then, the patient must be controlled. If clinical and radiological findings and pulmonary function tests are improved, the dose will be reduced 5–10 mg every 4–12 weeks until 10–15 mg/day. Maintenance dose must be continued for at least 6–8 months. The treatment period should be completed to 1 year. If the parameters are not improved, the initial dose must be continued for additional 4–6 weeks. Then initial dose is reduced to maintenance dose and the treatment is completed to 1 year. When symptoms reappear, the dose can be increased 10–20 mg/day above the maintenance dose for 2–4 weeks.

In acute respiratory failure or nonpulmonary sarcoidosis (cardiac, neurologic, etc.), 80–100 mg/day (1 mg/kg/day) prednisone may be needed.

During follow-up, review of systems, physical examination, blood tests (complete blood count [cbc], creatinine, calcium, Alanine aminotransferase (ALT), Aspartate aminotransferase (AST), Alkaline phosphatase (ALP), 25 hydroxyvitamin D, 1.25 hydroxyvitamin D), Electrocardiogram (EKG), and chest X-ray must be done every year. 24-h urine calcium must be evaluated at diagnosis and as indicated by symptoms. High-resolution computed tomography (HRCT), Magnetic resonance imaging (MRI), Holter, echocardiogram, and Thyroid-stimulating hormone (TSH) must be evaluated as indicated by symptoms. Bone density must be evaluated when corticosteroids started and then every 3 years.[16]

Serum angiotensin-converting enzyme (ACE) levels are elevated in 60% of sarcoidosis patients. Generally, sarcoidal granulomas produce ACE. However, serum ACE levels are not found useful in managing sarcoidosis. Furthermore, ACE inhibitor drugs suppress ACE levels.[16],[22],[27]

Relapses are frequent. Worsening of symptoms, radiological abnormalities, and pulmonary functions (10% decrease in FVC or TLC; decrease in PaO2; increase in alveolar-arterial oxygen gradient) are indicators of relapse. In these patients, lifelong low-dose treatment (≤0.25 mg/kg/day or 0.25–0.5 mg/kg/alternate days) may be required.[28]

In follow-up, symptoms of the patient are the most important parameter. Further, improvement in radiological abnormalities and pulmonary functions (10% increase in FVC, TLC; 20% increase in DLCO; 4 mmHg increase in PaO2; 4 mmHg decrease in alveolar-arterial oxygen gradient) is important to decide tapering prednisone dose. Hence, spirometry, DLCO, and oximetry must be done every 3–4 months follow-up and lung volumes must be measured every 12–24 months.[13]

Sometimes, symptoms may be discordant with radiological findings and pulmonary functions. In these patients, follow-up will help us. We must avoid early administration of corticosteroid therapy because it is related with relapsing disease.[13]

There are many adverse effects of systemic corticosteroid therapy. Weight gain, Cushingoid appearance, hirsutism, skin thinning, striae, posterior subcapsular cataract, exophthalmos, fluid retention, gastric irritation, steatohepatitis, increased risk of infections, hyperglycemia, psychiatric abnormalities, avascular necrosis, osteoporosis, myopathy, and leukocytosis are some of them. Before starting corticosteroid therapy, patient must be warned. The patient should be advised to pay attention to diet, salt, and sugar consumption.[16] For prevention of gastric irritation, proton pump inhibitors may be prescribed. Prevention of corticosteroid-induced osteoporosis is complex. Because sarcoid granulomas produce 1,25 hydroxyvitamin D. Further, calcium supplements may cause hypercalcemia and hypercalciuria. If there is not any hypercalcemia and hypercalciuria at the beginning of the treatment, 1200 mg/day calcium and 800 international unit/day Vitamin D intake is suggested. To prevent the risk of nephrolithiasis, dietary sources (milk, cheese, etc., of calcium must be preferred. Calcium and Vitamin D supplementation should be stopped when the corticosteroid therapy stopped. Bisphosphonates are recommended for prevention of bone loss for only patients with high fracture risk such as postmenopausal women or ≥50-year-old men who will use ≥7.5 mg/day prednisone for at least 3 months.[22],[27]

  Second-Line Agents Top

In some situations, corticosteroid therapy cannot be continued:

  • Patient cannot tolerate the adverse effects of corticosteroids
  • The disease progress and cannot be controlled despite moderate dose of corticosteroids (7.5–40 mg/day prednisone)
  • Refusal of patient to take corticosteroids.

Agents used for the treatment of pulmonary sarcoidosis refractory to corticosteroid therapy are methotrexate, azathioprine, leflunomide, and mycophenolate. They may be used alone or with corticosteroids. At the end stage of pulmonary sarcoidosis, organ transplantation may be performed.[14]

Before changing corticosteroid therapy to second-line agents, patients should be asked whether they use medications regularly. Further, they must be evaluated for infections, pulmonary embolism, or pulmonary hypertension.[22],[29],[30]

End-stage lung fibrosis is one of the causes of corticosteroid unresponsiveness. If there is end-stage lung fibrosis, it is also unresponsive to other immunosuppressive drugs. To distinguish whether there is active inflammation or not is difficult, because chest imaging and pulmonary function tests are not precise enough. Before lung transplantation, immunosuppressive therapy is generally tried.[31]


Methotrexate is the most commonly used drug in the treatment of pulmonary sarcoidosis refractory to corticosteroid therapy. It is an anti-inflammatory, immunosuppressive, and antimetabolite drug. It can be used for pulmonary sarcoidosis patients and also skin, eye, and central nervous system involvement.[32] Clinical response rate of methotrexate for pulmonary sarcoidosis is 40%–60%.[22],[33],[34] Before using methotrexate, cbc, aminotransferases, alkaline phosphatase, bilirubin, creatinine, albumin, and hepatitis B and C viral testing must be evaluated. Patients with liver disease (aminotransferases level above two times the upper limit of normal or chronic hepatitis B or C infection) or renal disease (creatinine clearance <30 ml/min) cannot use methotrexate. Further, methotrexate is contraindicated in chronic alcohol users and pregnant women.

After initiation of the therapy, these blood tests other than viral panel must be assessed every 3–6 weeks until stable dose of the drug and then continued every 4–12 weeks. If aminotransferases increased without any cause, methotrexate dose must be tapered and then stopped. Hepatic toxicity may be occult. Hence, some authors suggest liver biopsy in these situations: (1) total dose of methotrexate achieved to 1 g; (2) 18–24 months of therapy; (3) 6 of 12 aminotransferases in a year are abnormal.[32],[35]

Methotrexate has either oral or intramuscular forms. Generally, oral forms are preferred and 5–7.5 mg/week is the beginning dosage. Then, every 2 weeks, 2.5 mg/week is increased until 10–15 mg/week. If there is refractory nausea or unresponsive disease although 15 mg/week after 3–6 months of oral therapy, intramuscular form of the drug must be used.[32]

Methotrexate may be used alone or with corticosteroid therapy. By using low-dose methotrexate plus corticosteroid therapy, corticosteroid dose may be tapered with improvement of pulmonary functions. In patients who had methotrexate alone, adverse effects were seen in 30% of patients. Hence, combination therapy is generally preferred.[36],[37] In the disease refractory to methotrexate, one of the other second-line drugs (azathioprine, leflunomide, or mycophenolate) may be combined with methotrexate.[33]

The most serious side effects of methotrexate are leukopenia, hepatic fibrosis, and interstitial pneumonitis. Hepatic fibrosis may be seen approximately in 10% of cases when the total dose exceeds 5 g. To distinguish hepatic toxicity from hepatic sarcoidosis, liver biopsy is needed.[22],[38]

Methotrexate-induced interstitial pneumonitis is another adverse effect which is difficult to distinguish from progressive sarcoidosis-related interstitial lung disease. Ground-glass opacities, centrilobular nodules, and increased reticular opacities are typical in methotrexate-induced pneumonitis. Rarely, pleural effusions may be seen. These changes recover after stopping the drug. Blood eosinophilia is another finding that is more likely seen in methotrexate-induced interstitial pneumonitis than progression of sarcoidosis.[39],[40],[41]

Other adverse effects of methotrexate are teratogenicity, suppression of gonadal functions, nausea, alopecia, skin rash, and lymphoproliferative disorders. Some of the patients with lymphoproliferative disorder may regress after stopping methotrexate.[42],[43]

Folic acid (1 mg/day or 5 mg/weekly) is routinely given to patients on chronic methotrexate therapy to reduce myelosuppression risk. Cbc must be evaluated every 1–2 months.[40]


Azathioprine suppresses cellular immunity and inhibits lymphocyte proliferation via affecting DNA and RNA synthesis. It is used in patients with methotrexate therapy failure. The mechanism of azathioprine in sarcoidosis treatment is not clear. Azathioprine is generally used with corticosteroids.[44],[45] Improvements in patients are similar in azathioprine and methotrexate groups, except for a high infection rate with azathioprine.[36]

Before initiating azathioprine, cbc, aminotransferases, creatinine, and serum albumin must be evaluated. Further, thiopurine-S-methyltransferase (TPMT) genotyping and/or serum TPMT enzyme activity levels generally may be assessed. Because azathioprine toxicity is related to its metabolites and TPMT is the enzyme that converts azathioprine to its metabolites.[46]

Azathioprine's starting dose is 50 mg/day orally. The dose is increased by 25 mg every 2–3 weeks until the maintenance dose (2 mg/kg, maximum 200 mg/day). Then, white blood cell count (WBC) must be monitored every week during dose escalation and every 8–12 weeks in stable period. If WBC falls to 4000/mm3, azathioprine dose must be reduced. Further, serum aminotransferases must be evaluated every 8–12 weeks in the first several months, and then, less frequents checks are needed. After 3–6 months, prominent response to therapy can be raised.

Side effects of azathioprine are gastrointestinal complaints (nausea, vomiting, and diarrhea), fever, rash, malaise, and hematologic problems (suppression of all blood cell lines). Gastrointestinal side effects may be reduced by taking the drug with meal. Hematologic problems may be difficult to discriminate from suppression of bone marrow related to sarcoidosis. Other side effects are increase in aminotransferases and risk of malignancy.[31]


Leflunomide is an antimetabolite drug. Generally, used for extrapulmonary sarcoidosis, the usage in pulmonary sarcoidosis is rare.[47],[48],[49] Before initiating leflunomide, cbc, aminotransferases, creatinine, serum albumin, and hepatitis B and C must be evaluated. Patients with aminotransferases level above two times the upper limit of normal or chronic hepatitis infection cannot use leflunomide. Alcohol avoidance and reliable contraception method are recommended during leflunomide therapy.[31]

Initiation dose of leflunomide is 20 mg/day. Alternatively, it can be 10 mg/day and can be increased to 20 mg/day. After 6–12 weeks, improvement in lung function occurs.[47]

Serum albumin and liver function tests must be monitored every 2–4 weeks for the first 3 months, followed by monitoring every 8–12 weeks for the next 3 months and every 12 weeks thereafter.[35]

Nausea, diarrhea, rash, peripheral neuropathy, abdominal pain, and hepatotoxicity are the most common side effects.[33],[50]

Mycophenolate mofetil

Mycophenolate mofetil is a lymphocyte proliferation and activity inhibitor used in rheumatic disease-related interstitial lung diseases. Usage in sarcoidosis is limited. It can be used as a steroid-sparing agent. Nausea, diarrhea, and neutropenia are the most common side effects.[51],[52]

Other drugs

Tumor necrosis factor alpha antagonists

In pulmonary sarcoidosis refractory to corticosteroids and one of the second-line agents, we can use tumor necrosis factor alpha (TNF-α) antagonists. TNF-α is related to inflammation and maintenance of granuloma in sarcoidosis.[53],[54]

Infliximab, adalimumab, and etanercept are the TNF antagonists assessed in pulmonary sarcoidosis. Before initiating one of them, patient must be evaluated for latent infections including tuberculosis and hepatitis B and C. Hence, tuberculin skin test or peripheral blood interferon release assay for latent tuberculosis; as well as HbsAg, anti-HBc, and anti-HCV tests for hepatitis must be evaluated.[55],[56]

Infliximab is a monoclonal antibody which neutralizes TNF-α. It was evaluated in pulmonary and extrapulmonary sarcoidosis.[57],[58] Administration dose is 3–5 mg/kg intravenous infusion at 0, 2, 6, and 12 weeks. The optimal frequency and duration of infliximab in pulmonary sarcoidosis are unknown. Especially extrapulmonary sarcoidosis, patients receive more benefit than pulmonary sarcoidosis in long-term therapy.[56],[57],[58],[59] Sarcoidosis patients with peripheral blood CD4+ T-cell lymphopenia who are resistance to immunosuppressant may be more likely to respond infliximab.[60]

Adalimumab is a human anti-TNF antibody. In some case series, improvement in extrapulmonary sarcoidosis was described. However, effectiveness in pulmonary sarcoidosis is not certain.[61] It is administered by subcutaneously. Optimal dose in sarcoidosis is unknown; however, in some case series, it was used as 40 mg/every week.[62]

Etanercept is a soluble TNF-α receptor fusion protein which binds TNF-α. It was assessed in a clinical trial of stage 2–3 pulmonary sarcoidosis patients. However, because of treatment failure, the trial was stopped.[63]

TNF-α antagonists can be combined with corticosteroids, methotrexate, or azathioprine in some diseases such as Crohn disease or rheumatoid arthritis. However, data in sarcoidosis are insufficient.

Off-label investigational drugs

Cyclophosphamide, rituximab, golimumab, ustekinumab, chloroquine, hydroxychloroquine, and antimycobacterial therapy (rifampin, ethambutol, levofloxacin, and azithromycin) were tried in sarcoidosis but are not commonly used due to side effects or inadequate data.[31]

  Lung Transplantation Top

Lung transplantation may be promising to Stage IV sarcoidosis patients who have advanced pulmonary fibrosis and pulmonary hypertension. Timing of transplantation is not certain, but FVC less than 1.5 L (or <50% of predicted) and respiratory failure or pulmonary hypertension related to sarcoidosis are the features that predict transplantation requirement. Bilateral lung transplantation is more preferred than single-lung transplantation.[64] In patients with cardiac involvement, heart and lung transplantation must be done.[65] Recurrence of sarcoidosis after lung transplantation is very rare and generally disappears in 3 months.[66],[67]

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

  References Top

Rossman MD, Kreider ME. Lesson learned from ACCESS (A Case Controlled Etiologic Study of Sarcoidosis). Proc Am Thorac Soc 2007;4:453-6.  Back to cited text no. 1
Rossman MD, Thompson B, Frederick M, Iannuzzi MC, Rybicki BA, Pander JP, et al. HLA and environmental interactions in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2008;25:125-32.  Back to cited text no. 2
Patompong Ungprasert MS, Ryu JH, Matteson EL. MPH clinical manifestations, diagnosis, and treatment of sarcoidosis. Mayo Clin Proc Inn Qual Out 2019;3:358-75.  Back to cited text no. 3
Baughman RP, Teirstein AS, Judson MA, Rossman MD, Yeager H Jr., Bresnitz EA, et al. Clinical characteristics of patients in a case control study of sarcoidosis. Am J Respir Crit Care Med 2001;164:1885-9.  Back to cited text no. 4
Ungprasert P, Carmona EM, Utz JP, Ryu JH, Crowson CS, Matteson EL. Epidemiology of sarcoidosis 1946-2013: A population-based study. Mayo Clin Proc 2016;91:183-8.  Back to cited text no. 5
Rybicki BA, Major M, Popovich J Jr., Maliarik MJ, Iannuzzi MC. Racial differences in sarcoidosis incidence: A 5-year study in a health maintenance organization. Am J Epidemiol 1997;145:234-41.  Back to cited text no. 6
Baughman RP, Field S, Costabel U, Crystal RG, Culver DA, Drent M, et al. Sarcoidosis in America. Analysis based on health care use. Ann Am Thorac Soc 2016;13:1244-52.  Back to cited text no. 7
Gribbin J, Hubbard RB, Le Jeune I, Smith CJ, West J, Tata LJ. Incidence and mortality of idiopathic pulmonary fibrosis and sarcoidosis in the UK. Thorax 2006;61:980-5.  Back to cited text no. 8
Arkema EV, Grunewald J, Kullberg S, Eklund A, Askling J. Sarcoidosis incidence and prevalence: A nationwide register-based assessment in Sweden. Eur Respir J 2016;48:1690-9.  Back to cited text no. 9
Morimoto T, Azuma A, Abe S, Usuki J, Kudoh S, Sugisaki K, et al. Epidemiology of sarcoidosis in Japan. Eur Respir J 2008;31:372-9.  Back to cited text no. 10
Park JE, Kim YS, Kang MJ, Kim CJ, Han CH, Lee SM, et al. Prevalence, incidence, and mortality of sarcoidosis in Korea, 2003-2015: A nationwide population-based study. Respir Med 2018;144S: S28-34.  Back to cited text no. 11
Judson MA, Boan AD, Lackland DT. The clinical course of sarcoidosis: Presentation, diagnosis, and treatment in a large white and black cohort in the United States. Sarcoidosis Vasc Diffuse Lung Dis 2012;29:119-27.  Back to cited text no. 12
Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis. N Engl J Med 2007;357:2153-65.  Back to cited text no. 13
Baughman RP, Grutters JC. New treatment strategies for pulmonary sarcoidosis: Antimetabolites, biological drugs, and other treatment approaches. Lancet Respir Med 2015;3:813-22.  Back to cited text no. 14
Wijsenbeek MS, Culver DA. Treatment of sarcoidosis. Clin Chest Med 2015;36:751-67.  Back to cited text no. 15
Ungprasert P, Crowson CS, Carmona EM, Matteson EL. Outcome of pulmonary sarcoidosis: A population-based study 1976-2013. Sarcoidosis Vasc Diffuse Lung Dis 2018;35:123-8.  Back to cited text no. 17
Hillerdal G, Nöu E, Osterman K, Schmekel B. Sarcoidosis: Epidemiology and prognosis. A 15-year European study. Am Rev Respir Dis 1984;130:29-32.  Back to cited text no. 18
Nagai S, Shigematsu M, Hamada K, Izumi T. Clinical courses and prognoses of pulmonary sarcoidosis. Curr Opin Pulm Med 1999;5:293-8.  Back to cited text no. 19
Hunninghake GW, Costabel U, Ando M, Baughman R, Cordier JF, du Bois R, et al. ATS/ERS/WASOG statement on sarcoidosis. American Thoracic Society/European Respiratory Society/World Association of sarcoidosis and other granulomatous disorders. Sarcoidosis Vasc Diffuse Lung Dis 1999;16:149-73.  Back to cited text no. 20
Govender P, Berman JS. The diagnosis of sarcoidosis. Clin Chest Med 2015;36:585-602.  Back to cited text no. 21
Baughman RP, Costabel U, du Bois RM. Treatment of sarcoidosis. Clin Chest Med 2008;29:533-48.  Back to cited text no. 22
Gibson GJ, Prescott RJ, Muers MF, Middleton WG, Mitchell DN, Connolly CK, et al. British thoracic society sarcoidosis study: Effects of long term corticosteroid treatment. Thorax 1996;51:238-47.  Back to cited text no. 23
du Bois RM, Greenhalgh PM, Southcott AM, Johnson NM, Harris TA. Randomized trial of inhaled fluticasone propionate in chronic stable pulmonary sarcoidosis: A pilot study. Eur Respir J 1999;13:1345-50.  Back to cited text no. 24
Pietinalho A, Tukiainen P, Haahtela T, Persson T, Selroos O. 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;116:424-31.  Back to cited text no. 25
Bradley B, Branley HM, Egan JJ, Greaves MS, Hansell DM, Harrison NK, et al. Interstitial lung disease guideline: The British Thoracic Society in collaboration with the Thoracic Society of Australia and New Zealand and the Irish Thoracic Society. Thorax 2008;63 Suppl 5:v1-58.  Back to cited text no. 26
Baughman RP, Culver DA, Judson MA. A concise review of pulmonary sarcoidosis. Am J Respir Crit Care Med 2011;183:573-81.  Back to cited text no. 27
Paramothayan S, Jones PW. Corticosteroid therapy in pulmonary sarcoidosis: A systematic review. JAMA 2002;287:1301-7.  Back to cited text no. 28
Baughman RP, Lower EE. Fungal infections as a complication of therapy for sarcoidosis. QJM 2005;98:451-6.  Back to cited text no. 29
Shlobin OA, Nathan SD. Management of end-stage sarcoidosis: Pulmonary hypertension and lung transplantation. Eur Respir J 2012;39:1520-33.  Back to cited text no. 30
Cremers JP, Drent M, Bast A, Shigemitsu H, Baughman RP, Valeyre D, et al. Multinational evidence-based world association of sarcoidosis and other granulomatous disorders recommendations for the use of methotrexate in sarcoidosis: İntegrating systematic literature research and expert opinion of sarcoidologists worldwide. Curr Opin Pulm Med 2013;19:545-61.  Back to cited text no. 32
Baughman RP, Ohmichi M, Lower EE. Combination therapy for sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2001;18:133-7.  Back to cited text no. 33
Lower EE, Baughman RP. Prolonged use of methotrexate for sarcoidosis. Arch Intern Med 1995;155:846-51.  Back to cited text no. 34
Saag KG, Teng GG, Patkar NM, Anuntiyo J, Finney C, Curtis JR, et al. American college of rheumatology 2008 recommendations for the use of nonbiologic and biologic disease-modifying antirheumatic drugs in rheumatoid arthritis. Arthritis Rheum 2008;59:762-84.  Back to cited text no. 35
Vorselaars AD, Wuyts WA, Vorselaars VM, Zanen P, Deneer VH, Veltkamp M, et al. Methotrexate vs azathioprine in second-line therapy of sarcoidosis. Chest 2013;144:805-12.  Back to cited text no. 36
Gavrysyuk V, Merenkova E, Gumeniuk G, Gumeniuk M, Dziublyk Y. [Effectiveness and safety of methotrexate monotherapy in patients with pulmonary sarcoidosis]. Georgian Med News. 2018 Oct;(283):34-38.  Back to cited text no. 37
Baughman RP, Koehler A, Bejarano PA, Lower EE, Weber FL Jr. Role of liver function tests in detecting methotrexate-induced liver damage in sarcoidosis. Arch Intern Med 2003;163:615-20.  Back to cited text no. 38
Schnabel A, Richter C, Bauerfeind S, Gross WL. Bronchoalveolar lavage cell profile in methotrexate induced pneumonitis. Thorax 1997;52:377-9.  Back to cited text no. 39
Inokuma S, Kono H, Kohno Y, Hiramatsu K, Ito K, Shiratori K, et al. Methotrexate-induced lung injury in patients with rheumatoid arthritis occurs with peripheral blood lymphocyte count decrease. Ann Rheum Dis 2006;65:1113-4.  Back to cited text no. 40
Chikura B, Sathi N, Lane S, Dawson JK. Variation of immunological response in methotrexate-induced pneumonitis. Rheumatology (Oxford) 2008;47:1647-50.  Back to cited text no. 41
Niitsu N, Okamoto M, Nakamine H, Hirano M. Clinicopathologic correlations of diffuse large B-cell lymphoma in rheumatoid arthritis patients treated with methotrexate. Cancer Sci 2010;101:1309-13.  Back to cited text no. 42
Hoshida Y, Xu JX, Fujita S, Nakamichi I, Ikeda J, Tomita Y, et al. Lymphoproliferative disorders in rheumatoid arthritis: Clinicopathological analysis of 76 cases in relation to methotrexate medication. J Rheumatol 2007;34:322-31.  Back to cited text no. 43
Pacheco Y, Marechal C, Marechal F, Biot N, Perrin Fayolle M. Azathioprine treatment of chronic pulmonary sarcoidosis. Sarcoidosis 1985;2:107-13.  Back to cited text no. 44
Müller-Quernheim J, Kienast K, Held M, Pfeifer S, Costabel U. Treatment of chronic sarcoidosis with an azathioprine/prednisolone regimen. Eur Respir J 1999;14:1117-22.  Back to cited text no. 45
Bakker JA, Drent M, Bierau J. Relevance of pharmacogenetic aspects of mercaptopurine metabolism in the treatment of interstitial lung disease. Curr Opin Pulm Med 2007;13:458-63.  Back to cited text no. 46
Baughman RP, Lower EE. Leflunomide for chronic sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2004;21:43-8.  Back to cited text no. 47
Modrykamien A, Arrossi A, Reddy A. A 50-year-old man with stage 2 sarcoidosis with pleural involvement. J Hosp Med 2009;4:E1-3.  Back to cited text no. 48
Majithia V, Sanders S, Harisdangkul V, Wilson JG. Successful treatment of sarcoidosis with leflunomide. Rheumatology (Oxford) 2003;42:700-2.  Back to cited text no. 49
Emery P, Breedveld FC, Lemmel EM, Kaltwasser JP, Dawes PT, Gömör B, et al. A comparison of the efficacy and safety of leflunomide and methotrexate for the treatment of rheumatoid arthritis. Rheumatology (Oxford) 2000;39:655-65.  Back to cited text no. 50
Kouba DJ, Mimouni D, Rencic A, Nousari HC. Mycophenolate mofetil may serve as a steroid-sparing agent for sarcoidosis. Br J Dermatol 2003;148:147-8.  Back to cited text no. 51
Kalajian AH, Van Meter JR, Callen JP. Sarcoidal anemia and leukopenia treated with methotrexate and mycophenolate mofetil. Arch Dermatol 2009;145:905-9.  Back to cited text no. 52
Baughman RP, Lower EE, Drent M. Inhibitors of tumor necrosis factor (TNF) in sarcoidosis: Who, what, and how to use them. Sarcoidosis Vasc Diffuse Lung Dis 2008;25:76-89.  Back to cited text no. 53
Bargagli E, Olivieri C, Rottoli P. Cytokine modulators in the treatment of sarcoidosis. Rheumatol Int 2011;31:1539-44.  Back to cited text no. 54
Baughman RP, Drent M, Kavuru M, Judson MA, Costabel U, du Bois R, et al. Infliximab therapy in patients with chronic sarcoidosis and pulmonary involvement. Am J RespirCrit Care Med 2006;174:795-802.  Back to cited text no. 56
Hostettler KE, Studler U, Tamm M, Brutsche MH. Long-term treatment with infliximab in patients with sarcoidosis. Respiration 2012;83:218-24.  Back to cited text no. 57
Baughman RP, Lower EE. Infliximab for refractory sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2001;18:70-4.  Back to cited text no. 58
Rossman MD, Newman LS, Baughman RP, Teirstein A, Weinberger SE, Miller W Jr, et al. A double-blinded, randomized, placebo-controlled trial of infliximab in subjects with active pulmonary sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis 2006;23:201-8.  Back to cited text no. 59
Crouser ED, Lozanski G, Fox CC, Hauswirth DW, Raveendran R, Julian MW. The CD4+lymphopenic sarcoidosis phenotype is highly responsive to anti-tumor necrosis factor-{alpha} therapy. Chest 2010;137:1432-5.  Back to cited text no. 60
Crommelin HA, van der Burg LM, Vorselaars AD, Drent M, van Moorsel CH, Rijkers GT, et al. Efficacy of adalimumab in sarcoidosis patients who developed intolerance to infliximab. Respir Med 2016;115:72-7.  Back to cited text no. 61
Minnis PA, Poland M, Keane MP, Donnelly SC. Adalimumab for refractory pulmonary sarcoidosis. Ir J Med Sci 2016;185:969-71.  Back to cited text no. 62
Utz JP, Limper AH, Kalra S, Specks U, Scott JP, Vuk-Pavlovic Z, et al. Etanercept for the treatment of stage II and III progressive pulmonary sarcoidosis. Chest 2003;124:177-85.  Back to cited text no. 63
Taimeh Z, Hertz MI, Shumway S, Pritzker M. Lung transplantation for pulmonary sarcoidosis. Twenty-five years of experience in the USA. Thorax 2016;71:378-9.  Back to cited text no. 64
Fadel E, Mercier O, Mussot S, Leroy-Ladurie F, Cerrina J, Chapelier A, et al. Long-term outcome of double-lung and heart-lung transplantation for pulmonary hypertension: A comparative retrospective study of 219 patients. Eur J Cardiothorac Surg 2010;38:277-84.  Back to cited text no. 65
Johnson BA, Duncan SR, Ohori NP, Paradis IL, Yousem SA, Grgurich WF, et al. Recurrence of sarcoidosis in pulmonary allograft recipients. Am Rev Respir Dis 1993;148:1373-7.  Back to cited text no. 66
Carré P, Rouquette I, Durand D, Didier A, Dahan M, Fournial G, et al. Recurrence of sarcoidosis in a human lung allograft. Transplant Proc 1995;27:1686.  Back to cited text no. 67


  [Table 1], [Table 2]


    Similar in PUBMED
   Search Pubmed for
   Search in Google Scholar for
 Related articles
    Access Statistics
    Email Alert *
    Add to My List *
* Registration required (free)  

  Clinical Manifes...Treatment of Pul...
  In this article
Second-Line Agents
Lung Transplantation
Article Tables

 Article Access Statistics
    PDF Downloaded118    
    Comments [Add]    

Recommend this journal