INTRODUCTION — Sarcoidosis is a multisystem disease of unknown etiology characterized by tissue infiltration with noncaseating granulomas. The granulomas may occur in any organ, but the most frequently affected sites are the lungs, lymph nodes, skin, eyes, and liver. Patients with pulmonary sarcoidosis are most often asymptomatic at presentation. When symptomatic, patients usually report dyspnea, cough, or nonspecific chest discomfort. Spontaneous resolution of the disease is common, but progressive lung disease occurs in approximately 25 percent and disabling organ failure in up to 10 percent [1-3].

Glucocorticoids (also called corticosteroids) have long been the most commonly used agents for the treatment of pulmonary sarcoidosis, as they appear to attenuate the granulomatous inflammatory process. The key questions regarding the treatment of sarcoidosis with glucocorticoids are the following:

●What are the indications for treatment?

●When should therapy be started?

●What is the optimal duration of therapy?

●How should the disease course and the response to therapy be monitored?

●Does treatment alter the course of pulmonary sarcoidosis?

An overview of the initial treatment of sarcoidosis will be presented here. The clinical manifestations and diagnostic evaluation of sarcoidosis and the treatment of sarcoidosis with alternatives to glucocorticoids are discussed separately. (See "Clinical manifestations and diagnosis of pulmonary sarcoidosis" and "Treatment of pulmonary sarcoidosis: Disease refractory to glucocorticoid therapy".)

OVERVIEW — Most patients with pulmonary sarcoidosis do not require treatment, as a high proportion have asymptomatic, nonprogressive disease or experience a spontaneous remission. For those with more severe lung involvement, therapy of sarcoidosis is aimed at reducing the burden of granulomatous inflammation and preventing the development of irreversible end-organ damage (eg, honeycombing and fibrotic lung disease), while avoiding excess toxicity from medications. The cause of sarcoidosis is unknown, and clinical trial data are limited, so the majority of treatment decisions are based on observation and expert opinion.

●Initial therapy – Oral glucocorticoids have been the most commonly used agents for the relief of symptoms and control of potentially disabling respiratory impairment from pulmonary sarcoidosis, even if they do not cure the disease [1,4-6].

Prior to initiating therapy, patients are assessed for comorbid diseases that may contribute to their symptoms but not respond to glucocorticoid therapy (eg, heart failure, thromboembolic disease, pulmonary hypertension) [5]. In addition, infection with Mycobacterium tuberculosis must be excluded. Testing generally includes tuberculous skin test or interferon-gamma release assay, pulmonary function tests, high resolution computed tomography (HRCT) scan, and often an echocardiogram. (See "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Epidemiology, pathogenesis, and diagnostic evaluation in adults".)

●Clinical response – For patients who experience clinical improvement, glucocorticoid therapy is usually tapered gradually to 10 to 15 mg/day and continued for a total of 12 months, longer if the patient has recurrence of symptoms and radiographic opacities.

●Insufficient response or intolerance of glucocorticoids – While the majority of patients respond to glucocorticoid therapy, some patients do not respond despite an adequate trial of therapy (eg, the equivalent of prednisone ≥10 mg daily for at least three months). Other patients may be intolerant of glucocorticoids and be candidates for immunosuppressive therapy on that basis. Intensification of therapy for these patients typically involves immunosuppressive agents (eg, methotrexate, azathioprine, leflunomide, or tumor necrosis factor-alpha inhibitors). Referral to a sarcoidosis center may be prudent. The management of pulmonary sarcoidosis that is refractory to oral glucocorticoids is described separately. (See "Treatment of pulmonary sarcoidosis: Disease refractory to glucocorticoid therapy", section on 'Indications'.)

WHEN TO OBSERVE WITHOUT THERAPY — Glucocorticoid therapy is not indicated in the following groups of asymptomatic patients [7]:

●Asymptomatic patients with stage I radiographic changes (table 1). Approximately 60 to 80 percent of such patients have a spontaneous remission.

●Asymptomatic patients with stage II (table 1) radiographic changes and normal or mildly abnormal lung function (mild restrictive or obstructive findings with normal gas exchange). These patients are followed for three to six months to identify progression of disease before instituting therapy. In this setting, it is important to document progressive impairment of lung function or gas exchange before starting therapy, because approximately 50 percent of untreated patients with stage II radiographic changes will have radiographic resolution by 36 months. (See 'Inhaled glucocorticoid therapy' below.)

●Asymptomatic patients with stage III disease (table 1) and normal or mildly abnormal lung function. These patients can also be closely followed for three to six months. However, because only approximately 33 percent of untreated patients with stage III radiographic changes show disease resolution after five years, the majority of these patients will require therapy.

A multicenter British study examined the question of whether patients with asymptomatic pulmonary parenchymal disease (stage II or III) would have a better long-term outcome if they received long-term (18 months) glucocorticoid therapy aimed at optimizing the radiographic appearance, rather than continued observation with treatment initiation if symptoms worsened or lung function deteriorated [8]. At five years, the average vital capacity was higher by 9 percent of the predicted value in the long-term glucocorticoid group. However, two-thirds of those who received glucocorticoid therapy experienced adverse effects, including weight gain, cushingoid features, and gastrointestinal disturbances.

MECHANISM OF ACTION OF GLUCOCORTICOIDS — The exact mechanism of action of glucocorticoids in the treatment of sarcoidosis is unknown. Based on pathologic studies, sarcoid granulomas have a tightly packed central area, composed of macrophages, epithelioid cells, and multinucleated giant cells. This central area is surrounded by lymphocytes, monocytes, mast cells, and fibroblasts. T lymphocytes are the prime drivers of the immune response. Several cytokines produced by these inflammatory cells, especially T lymphocytes have been implicated in the pathogenesis of granuloma formation and the subsequent development of fibrosis, including interleukin (IL)-1, IL-2, IL-2R, interferon-gamma, tumor necrosis factor (TNF)-alpha, and granulocyte-macrophage colony stimulating factor (GM-CSF). (See "Pathology and pathogenesis of sarcoidosis".)

Glucocorticoids appear to exert their effects on sarcoid granulomas through transcriptional regulation of glucocorticoid-receptor target genes and also non-genomic signal transduction pathways in lymphocytes and alveolar macrophages (figure 1) [1,4,9-11]. A number of the cytokines mentioned above that appear to participate in granulomatous inflammation are modulated by glucocorticoids. (See "Glucocorticoid effects on the immune system".)

ORAL GLUCOCORTICOID THERAPY — Oral glucocorticoid therapy generally improves symptoms (eg, cough and dyspnea) and radiographic abnormalities, at least initially. However, the known side effects of glucocorticoids and the uncertain effect of therapy on long-term outcome make it important to select patients carefully.

Indications for therapy — When assessing the indications for glucocorticoid therapy, it is helpful to keep in mind that certain features help to predict the likely course of disease. A longer period of watchful waiting prior to initiating therapy may be possible in patients with more favorable characteristics. Favorable characteristics include stage I disease, especially when associated with erythema nodosum, absence of symptoms, and European descent. Unfavorable prognostic features, in contrast, include the presence of symptoms (especially dyspnea), multisystem involvement (three or more organs involved), increasing chest radiographic opacities, extrapulmonary disease involving skin, bone, or joints (especially if age greater than 30 years), and African descent (only 12 percent with stage I disease show rapid recovery) [12,13].

Pulmonary sarcoidosis — The usual indication for therapy of pulmonary sarcoidosis is a combination of [3,7,14]:

●Bothersome pulmonary symptoms (eg, cough, shortness of breath, chest pain or discomfort, hemoptysis).

●Deteriorating lung function, as assessed by serial testing at three to six month intervals, that demonstrates one or more of the following: a fall in total lung capacity (TLC) of 10 percent or more; a fall in forced vital capacity (FVC) of 15 percent or more; a decrease in diffusing capacity (DLCO) of 20 percent or more; or worsened gas exchange at rest (eg, a decrease in oxygen saturation on pulse oximetry of four or more percent) or with exercise.

●Progressive radiographic changes, including: worsening of interstitial opacities, development of cavities, progression of fibrosis with honeycombing, or development of signs of pulmonary hypertension.

Rarely, patients will present with severe enough initial disease that they should be started on glucocorticoid therapy without waiting for documented radiographic or physiologic progression. These patients typically have bothersome and worsening symptoms, values of FVC and forced expiratory volume in one second (FEV₁) below 70 percent of predicted, a diffusing capacity below 60 percent of predicted, and/or an oxygen saturation of 90 percent or less, and widespread radiographic opacities.

Extrapulmonary sarcoidosis — In some patients with pulmonary sarcoidosis, the lung involvement is not severe enough to warrant treatment, but the concomitant extrapulmonary disease may indicate the need for therapy. The decision to treat extrapulmonary sarcoidosis should be based on the specific organ systems affected and on the degree of impairment identified through clinical and laboratory examination. Treatment of ocular, neurologic, myocardial, or renal sarcoidosis or hypercalcemia is indicated even when symptoms are slight, because severe loss of vision, fatal arrhythmias, or insidious renal damage may ensue [15]. The therapy of sarcoidosis affecting specific extrapulmonary organ systems is discussed separately. (See "Hypercalcemia in granulomatous diseases" and "Clinical manifestations and diagnosis of cardiac sarcoidosis" and "Neurologic sarcoidosis" and "Kidney disease in sarcoidosis".)

Other potential indications for therapy include severe discomfort or inability to work as a result of fever, weakness, fatigue, arthralgia, disfiguring skin disease, upper airway disease, or hepatic insufficiency [16].

Dosage and administration — The optimal dose of glucocorticoids is not known, so choosing a dose requires balancing the likelihood of response against the risk of adverse effects [2,3,17,18]. The following approach is based on expert opinion as there are insufficient published data to support a specific approach.

Initial therapy — Therapy is usually initiated with oral prednisone at a daily dose of 0.3 to 0.6 mg/kg ideal body weight (usually 20 to 40 mg/day), depending on the severity of disease activity [2,19]. For patients with shortness of breath on exertion and slowly worsening radiographic opacities, the lower dose is usually adequate. For patients with rapidly progressive disease and severe impairment (eg, oxygen dependent), we favor using the higher end of the dose range.

The initial dose is continued for four to six weeks and then the patient is re-assessed. If the symptoms, radiographic abnormalities, and pulmonary function tests (eg, spirometry, diffusing capacity, ambulatory oximetry) are stable or improved, the dose is tapered (see 'Assessing the response' below). Tapering schedules vary, but a common schedule is to decrease by 5 to 10 mg decrements every 4 to 12 weeks down to 0.2 to 0.4 mg/kg (approximately 10 to 15 mg/day).

If the clinical and physiologic parameters are unimproved after four to six weeks at the initial dose, we continue that dose an additional four to six weeks. Most of the improvement with glucocorticoids is apparent in three to four weeks' time [3,20]. (See 'Assessing the response' below.)

High-dose oral glucocorticoid therapy (80 to 100 mg/day) may rarely be warranted in patients with acute respiratory failure or concomitant cardiac, neurologic, ocular, or upper airway disease [21-23]. This level is continued until the disease is under control (usually 4 to 12 weeks). Once improvement is achieved, the dose is tapered as described for the maintenance phase above. (See "Neurologic sarcoidosis" and "Clinical manifestations and diagnosis of cardiac sarcoidosis".)

Maintenance therapy — No formal data are available to guide maintenance dosing of oral glucocorticoids. Based on clinical experience, a maintenance dose of prednisone in the range of 0.25 to 0.4 mg/kg (usually 10 to 15 mg) per day will prevent worsening of disease [2]. Alternate day therapy with prednisone has also been used for maintenance after initial daily therapy to reduce the risk of adverse effects from the glucocorticoids, but few data are available to support its efficacy. Likely, the benefits are comparable to similar doses of daily glucocorticoid therapy [24].

During the maintenance phase, the patient is reassessed at 4 to 12 week intervals for evidence of symptomatic worsening or development of glucocorticoid-related adverse effects. (See 'Assessing the response' below and 'Adverse effects' below.)

Recurrence of symptoms, such as cough, dyspnea, and chest pain, is common (occurring in approximately 60 percent of patients), so we continue the maintenance dose for at least three to six to months, giving a total treatment period of approximately one year. Frequently, a brief course of higher doses (increases of 10 to 20 mg above the maintenance dose given for two to four weeks) is required to relieve an episode of recurrent symptoms. (See "Glucocorticoid withdrawal".)

The majority of patients are able to discontinue systemic glucocorticoids after one year [25]. However, approximately one-third will develop a relapse and require another course of therapy, and a small number of patients require more long-term or indefinite maintenance therapy to control their symptoms [26].

Duration of therapy — The proper length of therapy in patients who respond to treatment is not known [4,13,27]. Therapy must be given for at least three to six months to be effective and to reduce the likelihood of relapse. Relapses are frequent following reduction or withdrawal of therapy, ranging from 14 to 74 percent among those with disease of recent onset (≤5 years) [3]. Consequently, we usually aim for at least one year of therapy.

Lifelong low dose treatment (≤0.25 mg/kg per day, or 0.25 to 0.5 mg/kg on alternate days) may be required by a minority of patients who suffer frequent relapses.

Assessing the response — The optimal tools and timing for assessing the response to therapy in pulmonary sarcoidosis are unknown [1]. Due to the absence of a well-defined assessment tool, a combination of symptoms, physical examination, radiographic abnormalities, and pulmonary function tests is used to assess disease activity (table 2). Many experts believe that symptoms are the most important parameter to follow, although this approach depends on the reliability of the individual patient in perceiving and reporting symptoms. A difficult situation can arise when a patient experiences subjective improvement with glucocorticoid therapy without objective change. Due to the toxicity of glucocorticoid therapy, we try to avoid having symptoms be the lone factor in determining whether to continue treatment.

The pulmonary function tests that we follow at three- to four-month intervals are spirometry, diffusing capacity (DLCO), and ambulatory oximetry. We obtain lung volume measurements every 12 to 24 months.

A favorable response to glucocorticoid therapy is defined by:

●A decrease in symptoms, especially dyspnea, cough, hemoptysis, chest pain, or fatigue.

●A reduction in or clearing of radiographic abnormalities.

●Physiologic improvement, such as a 10 percent or greater increase in forced vital capacity (FVC) or total lung capacity (TLC), a 20 percent or greater increase in diffusing capacity (DLCO), or an improvement in gas exchange (eg, a 4 mmHg [0.53 kPa] or greater increase in the arterial tension of oxygen [PaO₂] or a decline of 4 mmHg [0.53 kPa] or more in the alveolar-arterial oxygen gradient at rest or during exercise).

Stabilization of radiographic abnormalities and lung function for prolonged periods of time (three to six months) should also be considered a positive response to treatment.

A relapse is typically characterized by:

●Worsening dyspnea, cough, or chest discomfort

●A fall of 10 percent or more in FVC or TLC

●Worsening of radiographic opacities, especially with development of cavities, honeycombing, or signs of pulmonary hypertension

●Decreased gas exchange at rest or with exercise

Sarcoidal granulomas produce angiotensin-converting enzyme (ACE), and serum ACE levels are elevated in 60 percent of patients with sarcoidosis [1]. However, following serum ACE levels has not been demonstrated to be useful in the management of sarcoidosis [28,29]. Additionally, angiotensin converting enzyme inhibitor therapy suppresses ACE levels [30].

In addition to monitoring the activity of pulmonary disease, it is also important to monitor patients with sarcoidosis for development of extrapulmonary disease. A general guideline and list of tests is provided in the table (table 2). An approach to monitoring sarcoidosis is presented separately. (See "Clinical manifestations and diagnosis of pulmonary sarcoidosis", section on 'Monitoring'.)

Efficacy — The balance of evidence suggests that oral glucocorticoids improve respiratory symptoms and radiographic abnormalities, although not necessarily pulmonary function tests [4,31-34]. However, assessment of the benefits of glucocorticoid therapy in the treatment of sarcoidosis remains problematic for the following reasons [31,35,36]:

●A large number of patients with sarcoidosis undergo spontaneous remission or have a benign clinical course (see 'Long-term outcome' below). However, no clear predictors of spontaneous remission or progression of disease have been identified. The marked variability in presentation and clinical course make it difficult to evaluate whether an apparent response to therapy reflects a treatment effect or the natural course of that patient's disease.

●There is no easy way to assess disease activity or severity, and symptoms may be discordant with results of pulmonary function testing and chest imaging, which makes it difficult to interpret the results of clinical studies or the response to therapy in an individual patient.

●There is a concern that early administration of systemic glucocorticoid therapy may actually increase the likelihood that the patient will develop relapsing disease, rather than a sustained remission [37-39]. A prospective series of 215 patients with recent onset sarcoidosis examined the effect of glucocorticoid therapy in the first six months of diagnosis on the need for ongoing therapy at the end of two years [40]. Among 95 who were not initially treated with glucocorticoids, only 8 percent were receiving therapy after two years. In contrast, of 110 patients who were on systemic therapy at baseline, 47 percent were on therapy after two years. One explanation for this observation is that treatment limited the body's innate ability to clear the disease, thus necessitating long-term therapy. An alternate explanation is that patients, who were not randomly assigned to treatment groups, were selected for therapy based on subtle indications that they had more severe disease [41].

The results of individual trials have been variable, probably due to variations in patient populations, prednisone dose, and duration of therapy [4,42,43]. The best evidence in favor of glucocorticoid therapy for pulmonary sarcoidosis comes from the largest systematic review that included 13 randomized trials comparing oral glucocorticoid therapy (equivalent to prednisolone 4 to 40 mg daily for 3 to 24 months) with placebo [31,36]. The analysis found that oral glucocorticoids improved chest radiograph opacities (RR 1.46 [95% CI, 1.01-2.09]), symptoms, and spirometry. However, lung function test results could not be grouped for statistical analysis, and at least two of the trials examined found no improvement in lung function [17,31]. Diffusing capacity was only assessed in a couple of trials, one without benefit and one found a modest improvement among patients with stage II disease (table 1) treated for 18 months, but not at interval assessments before 18 months [17,44,45].

The effect of one to two years of oral glucocorticoids on long-term disease outcomes is less clear, due to a paucity of data [46]. In a small trial that examined this question, 25 patients were assigned to prednisone or placebo (by alternating treatment groups rather than randomization) [42]. The prednisone group received 60 mg per day for one month, then 20 mg per day for five months or longer, depending on clinical course. After 10 years, symptoms were improved in both groups and radiographic stage was not different between the groups, although the only subjects with a normal chest radiograph were in the untreated group. Spirometric values were not different between the groups and diffusing capacity improved in both groups. It is possible that the method of assigning treatment groups introduced bias and affected the results.

Adverse effects — Numerous adverse effects have been attributed to chronic systemic glucocorticoid therapy (table 3). The identification and prevention of these adverse effects are discussed separately. (See "Major side effects of systemic glucocorticoids", section on 'Organ-based toxicity of systemic glucocorticoids' and "Treatment and prevention of Pneumocystis pneumonia in patients without HIV", section on 'Indications'.)

Prevention of glucocorticoid-induced bone loss is a complicated issue in patients with sarcoidosis compared with other glucocorticoid-requiring diseases, due to production of vitamin D by sarcoid granulomas and the risk of hypercalcemia and hypercalciuria with calcium supplementation. (See "Hypercalcemia in granulomatous diseases", section on 'Sarcoidosis'.)

We follow the following steps to guide preventive therapy:

●In the absence of prior hypercalcemia or hypercalciuria, we advise patients to take calcium-vitamin D supplements during systemic glucocorticoid therapy to achieve a total calcium intake of 1200 mg/day and a vitamin D intake of 800 international units/day. We prefer that calcium come from dietary sources (table 4), as much as possible (at least half), to reduce the risk of nephrolithiasis. At the completion of glucocorticoid therapy, calcium and vitamin D supplements should be stopped to prevent subsequent hypercalcemia. (See "Prevention and treatment of glucocorticoid-induced osteoporosis", section on 'Calcium and vitamin D' and "Calcium and vitamin D supplementation in osteoporosis", section on 'Dietary sources'.)

●Serum and urine calcium levels: If calcium supplementation (beyond dietary) is necessary, serum and urine calcium should be carefully monitored before starting supplements and during therapy. Urinary calcium excretion is best assessed by a 24 hour urine (normal <250 mg/day). Alternatively, a spot urinary calcium-creatinine ratio can be obtained, although it is less accurate. A ratio >0.2 suggests hypercalciuria.

●Serum 25-hydroxyvitamin D (calcidiol) and 1,25-dihydroxyvitamin D (calcitriol) should be measured prior to adding supplemental vitamin D and periodically during therapy. While 25-hydroxyvitamin D is often low in patients presenting with sarcoidosis, 1,25-hydroxyvitamin D can be normal or elevated due to production by activated macrophages. (See "Hypercalcemia in granulomatous diseases", section on 'Sarcoidosis'.)

●Assess the patient's risk factors for fragility fracture (table 5). Patients with risk factors may need a more formal assessment of fracture risk (eg, FRAX analysis and possibly bone density testing with dual-energy x-ray absorptiometry [DXA]) to determine whether additional therapy, such as bisphosphonates, is needed. (See "Clinical features and evaluation of glucocorticoid-induced osteoporosis", section on 'Fracture risk assessment'.)

●In general, bisphosphonates are recommended for prevention of bone loss and fractures in postmenopausal women and in men ≥50 years old who require systemic glucocorticoids ≥7.5 mg/day for longer than three months and are considered at high risk for bone fragility. For younger women and men, bisphosphonates are reserved for those who have had a fragility fracture or who have accelerated bone loss. (See "Prevention and treatment of glucocorticoid-induced osteoporosis".)

Relapses — Symptomatic relapses may occur during tapering of therapy or after discontinuation and are typically accompanied by declines in lung function, progression of radiographic abnormalities, or both. These parameters usually improve, at least partially, with retreatment.

If there is relapse of the disease after tapering prednisone, the dose is increased to the last effective dose and continued for a subsequent three to six months. If there is no improvement after three months, prednisone is increased back to the initial effective dose (20 to 40 mg daily) until there is improvement (usually three to six months).

For patients with an acute exacerbation (defined by criteria similar to those used for acute exacerbations idiopathic pulmonary fibrosis: decrease of pulmonary function tests [PFTs] more than 10 percent, worsening of symptoms not attributable to an identified cause, radiological worsening), we typically prescribe prednisone 20 mg/day for three weeks based upon observational data. A retrospective study of 36 patients with acute exacerbations of pulmonary sarcoidosis has shown that treatment with the equivalent of prednisone 20 mg/day for approximately 21 days resulted in improvement of symptoms and return of lung function to baseline [20]. Subsequent tapering is more gradual than the taper that resulted in a relapse. (See 'Maintenance therapy' above.)

If reactivation occurs after discontinuing prednisone, oral glucocorticoids are reinstituted following the dosing described for initial therapy. (See 'Initial therapy' above.)

Patients who improve and remain stable for more than one year following cessation of therapy have a low rate of relapse [24].

Refractory disease — For patients who are unable to tolerate the adverse effects of glucocorticoids, whose disease cannot be controlled on the equivalent of prednisone 10 to 15 mg or less, or who have evidence of disease progression despite a moderate dose of prednisone, an alternative immunosuppressive agent may be of benefit [47]. (See "Treatment of pulmonary sarcoidosis: Disease refractory to glucocorticoid therapy".)

INHALED GLUCOCORTICOID THERAPY — Inhaled glucocorticoids have been evaluated for the treatment of pulmonary sarcoidosis, but results are conflicting [17,31,44,47-54]. Inhaled glucocorticoids appear to modulate the alveolitis of sarcoidosis [52,53] and provide clinical benefit in some subjects; however, significant changes in lung function have not been seen [44,49,50,54]. As an example, one randomized trial of 2000 mcg/day of fluticasone in 44 patients found no significant differences in lung function; borderline improvements in cough, breathlessness, wheeze, and general health perception were noted [54].

Budesonide (800 to 1600 mcg twice daily) has been the most frequently studied inhaled glucocorticoid [44]. Inhaled fluticasone propionate can be used as alternative therapy (eg, 500 to 1000 mcg twice daily).

Many clinicians advise a trial (eg, for four to eight weeks) of inhaled glucocorticoids in the following settings although supportive data are limited:

●Cough with or without airway hyperreactivity

●Stage I or II disease (table 1) with only mild pulmonary symptoms or lung function abnormalities

●Use as an alternative to long-term low dose prednisone (5 to 10 mg daily) [44]

ADRENOCORTICOTROPIC HORMONE — There is no credible evidence that adrenocorticotropic hormone (ACTH), which is only available by injection, has any greater efficacy or safety than oral glucocorticoids [3,55,56]. ACTH exerts its antiinflammatory effects via stimulation of cortisol production by the adrenal glands and does not circumvent the adverse effects of hypercortisolism.

LONG-TERM OUTCOME — It has been estimated that spontaneous remission occurs in approximately 60 to 80 percent of patients with radiographic stage I disease, 50 to 60 percent with stage II disease, and less than 30 percent in stage III disease (table 1) [57]. The overall death rate from sarcoidosis is less than 5 percent [1].

Causes of death in sarcoidosis include:

●Progressive pulmonary fibrosis and cor pulmonale. (See "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Treatment and prognosis" and "Pulmonary hypertension due to lung disease and/or hypoxemia (group 3 pulmonary hypertension): Epidemiology, pathogenesis, and diagnostic evaluation in adults".)

●Pulmonary hemorrhage from aspergillomas developing in damaged lung tissue. (See "Treatment of chronic pulmonary aspergillosis".)

●Myocardial involvement contributes to mortality, although the exact portion of sarcoid deaths attributable to myocardial sarcoid varies among studies (eg, 2 to 50 percent). (See "Clinical manifestations and diagnosis of cardiac sarcoidosis" and "Clinical manifestations and diagnosis of cardiac sarcoidosis", section on 'Prevalence'.)

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Sarcoidosis".)

INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5^th to 6^th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10^th to 12^th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.

Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)

●Basics topics (see "Patient education: Sarcoidosis (The Basics)")

●Beyond the Basics topics (see "Patient education: Sarcoidosis (Beyond the Basics)")

SUMMARY AND RECOMMENDATIONS

●Most patients with pulmonary sarcoidosis do not require treatment, as a high proportion have asymptomatic, nonprogressive disease or experience a spontaneous remission. (See 'Overview' above.)

●For asymptomatic patients with pulmonary sarcoidosis and no significant extrapulmonary involvement, we pursue close observation rather than initiating therapy with oral glucocorticoids due to the high rate of spontaneous remission and the known adverse effects of systemic glucocorticoids (table 1). Careful monitoring of symptoms, chest radiograph, and pulmonary function is continued at three to six month intervals. (See 'Indications for therapy' above.)

●Indications for treatment of pulmonary sarcoidosis include evidence of progressive disease or, rarely, severe disease at presentation.

•For patients with pulmonary sarcoidosis causing bothersome symptoms and evidence of worsening radiographic opacities (stage II or III, (table 1)) and increasing pulmonary function impairment, we recommend initiation of oral glucocorticoids rather than continued observation (Grade 1B). (See 'Indications for therapy' above.)

•For patients who present with disabling symptoms, widespread radiographic abnormalities (stage II or III (table 1)), and moderate to severe impairment of pulmonary function, we suggest initiation of oral glucocorticoid therapy, rather than waiting for evidence of progression (Grade 2B). (See 'Initial therapy' above.)

●In our practice, the initial glucocorticoid regimen is the equivalent of prednisone 0.3 to 0.6 mg/kg ideal body weight (usually 20 to 40 mg/day). This dose of prednisone is continued for four to six weeks. If the symptoms, radiographic abnormalities, and pulmonary function tests are unimproved, we continue the initial dose for another four to six weeks. If these parameters are stable or improved, the dose of prednisone is tapered gradually. (See 'Initial therapy' above.)

●No formal data are available to guide maintenance dosing of oral glucocorticoids. We typically taper prednisone by 5 to 10 mg increments until a dose of 0.25 to 0.4 mg/kg (usually 10 to 15 mg) per day, as tolerated. This dose is continued for the maintenance dose for at least six to eight months, giving a total treatment period of approximately one year. (See 'Maintenance therapy' above.)

●The optimal tools and timing of assessment of a response to therapy are unknown. We monitor a combination of symptoms, physical examination, radiographic abnormalities, and pulmonary function tests (spirometry, diffusing capacity [DLCO], and ambulatory oximetry) at four to six week intervals during initial therapy and at 6 to 12 week intervals while on systemic glucocorticoids. (See 'Assessing the response' above.)

●For patients with cough (with or without airway hyperreactivity) who do not otherwise meet criteria for oral glucocorticoid therapy (eg, stage I or II radiographic disease (table 1) and mild pulmonary lung function abnormalities), we suggest initiating therapy with inhaled glucocorticoids (Grade 2B). We use the equivalent of budesonide 800 to 1600 mcg twice daily (eg, fluticasone propionate 500 to 1000 mcg twice daily). The inhaled glucocorticoid can be discontinued after four to eight weeks, if there is no evidence of benefit. Inhaled glucocorticoids can also be tried as an alternative to long-term low dose prednisone (eg, 5 to 10 daily) for chronic control of pulmonary sarcoid. (See 'Inhaled glucocorticoid therapy' above.)

●Chronic systemic glucocorticoid therapy has numerous adverse effects (table 3). The identification and prevention of these adverse effects are discussed separately. (See "Major side effects of systemic glucocorticoids", section on 'Organ-based toxicity of systemic glucocorticoids'.)

●For patients who are unable to tolerate the adverse effects of glucocorticoids, whose disease cannot be controlled on the equivalent of prednisone 10 to 15 mg or less, or who have evidence of disease progression despite a moderate dose of prednisone, an alternative immunosuppressive agent may be of benefit. (See "Treatment of pulmonary sarcoidosis: Disease refractory to glucocorticoid therapy".)