Introduction
Background
Sarcoidosis is a multisystemic granulomatous disease of unknown etiology with variable presentation, prognosis, and progression. Caesar Boeck first coined the term sarcoid in 1899 to describe one of the skin lesions of sarcoidosis because of its histologic resemblance to a sarcoma. In 1905, Boeck described a series of patients with sarcoid who presented with cough and nasal granulomas. These findings suggested the systemic nature of the disease. In 1915, Kusnitski and Bittorf described chest radiographic abnormalities in a patient with sarcoidosis.
Sarcoidosis almost always affects the respiratory system. Most patients present with the classic combination of bilateral hilar lymphadenopathy, parenchymal disease of the lung, and eye or skin lesions; however, virtually any organ in the body may be involved. At diagnosis, about 50% of patients are asymptomatic, 25% complain of cough or dyspnea, and 25% have or develop eye symptoms or skin lesions (eg, such as erythema nodosum, lupus pernio, plaques or scars).
When present, constitutional symptoms include weight loss, fatigue, weakness, and malaise. Symptoms of pulmonary involvement, such as dry cough and shortness of breath, develop in 20-30% of patients.
Bilateral hilar lymphadenopathy is the most common radiographic finding. Other radiographic findings include interstitial lung disease; occasional calcification of affected lymph nodes; and rarely, pleural effusions and thickening.
In general, sarcoidosis is a self-limiting subclinical process in 60-70% of cases. About 20-30% of patients are left with a variable degree of permanent lung damage. In 10-15% of the patients, sarcoidosis can become chronic. The incidence of ocular involvement is about 20-30%.
Because the disease so often involves thoracic structures, chest radiography plays a crucial role in the diagnosis, staging, and follow-up of sarcoidosis. The diagnosis is established when the clinical and radiographic findings are supported by histologic evidence of widespread noncaseating epithelioid cell granulomas in more than 1 organ or a positive Kveim-Stiltzbach skin test result.
For excellent patient education resources, visit eMedicine's Lung and Airway Center and Cold and Flu Center. Also, see eMedicine's patient education articles Collapsed Lung, Flu in Adults, and Coughs.
Related eMedicine topics:
Granulomatous Diseases of the Head and Neck
Lymphadenopathy
Related Medscape topics:
Specialty Site Radiology
CME Manifestations and Treatment of Sarcoidosis
CME Highlights from the Radiological Society of North America (RSNA) 93rd Scientific Assembly and Annual Meeting
Pathophysiology
Etiology
The etiology of sarcoidosis is unknown. Granulomatous inflammation is invariably present; some have speculated that this disease is a response to inhaled foreign material. Thoracic sarcoidosis is currently viewed as a disorder of immune regulation, but the antigenic agent or agents responsible for the disease remain elusive.
A deranged cellular immune response to an unidentified antigen, such as atypical tuberculosis (TB) or pine pollen, is possible. Mycobacterium species and, less likely, gram-negative bacteria have been implicated. However, cultures from affected tissue are almost always sterile. Additionally, no evidence suggests host-to-host transmission of the disease. However, some evidence implicates abnormal immune function.
The bronchoalveolar lavage fluid in patients with sarcoidosis contains an increased number of lymphocytes, especially the CD4 subset in patients with active sarcoidosis. The ratio of helper T cells to suppresser T cells is abnormal. Cell-mediated immunity is stimulated in the lung, resulting in the formation of characteristic epithelioid cell granulomas.
Activated alveolar macrophages and T lymphocytes play an important role in the development of sarcoidosis. T cells are responsible for an accumulation of CD4 cells and the release of interleukin (IL)–2 at sites of disease activity. This may be clinically manifest by an inverted CD4/CD8 ratio.
In sarcoidosis, a variety of biochemical mediators are released; these include IL-1 (a T-cell activator), fibronectin (fibroblast chemotactic factor), and alveolar macrophage-derived growth factor (stimulates fibrosis). The T-lymphocyte population includes a higher proportion of T-helper cells as compared with the population in normal lungs. These activated T cells release IL-2 (which stimulates the growth of T-helper or cytolytic cells), monocyte chemotactic factor (which attracts circulating monocytes), and immune interferon (which activates polyclonal B cells).
The production of TH1 cytokines, such as interferon and tumor necrosis factor (TNF), is also increased, with an associated increase in TNF receptors. TNF propagates inflammation; this has been demonstrated by the affective use of anti-TNF agents in the treatment of sarcoidosis.
B cells also play a role, as shown by B-cell hyperreactivity with immunoglobulin production.
The process described above may resolve spontaneously, or it may progress to form the noncaseating granulomas, which is the histologic hallmark of sarcoidosis. Progression of the granulomatous process to fibrosis may occur in 10-15% of patients.1
Histologic findings
Alveolitis is the earliest pathologic manifestation of sarcoidosis. The earliest change is an infiltrate of lymphocytes and histiocytes in the alveolar septa, which eventually progress to the typical granulomatous lesions. The intrathoracic involvement is characteristically most pronounced in peribronchovascular, interlobular septal, and pleural areas. This process affects the upper lobes of the lungs more severely.
The inflammatory response is a nongranulomatous interstitial pneumonitis involving the alveolar walls. T lymphocytes recruit macrophages, which lose their motility and are transformed into epithelioid cells. Conglomeration of these epithelioid cells, lymphocytes, peripheral fibroblasts, and multinucleated giant cells become interstitial granulomas. A fine network of reticular fibers is also present. Minimal central necrosis may rarely occur. Sarcoid granulomas are widely distributed. They congregate in lymph nodes and in organs rich with lymphoid tissues. In the lung, the granulomas are interstitial, located in the subpleural, septal, perivascular, and peribronchial spaces. In 10-20% of patients with sarcoidosis, interstitial granulomas progress to pulmonary fibrosis.
The histologic hallmark of sarcoidosis is the noncaseating granuloma, but this finding is by no means specific. These granulomas are the result of a nonspecific cell-mediated response and indistinguishable from those found in berylliosis, TB, leprosy, hypersensitivity pneumonitis, Crohn disease, primary biliary cirrhosis, fungal disease, and local sarcoid reactions seen in lymph node–draining neoplasms and sites of chronic inflammation. Thus, the diagnosis of sarcoidosis is established by exclusion.
Staging
The clinical staging of sarcoidosis is based on the pattern of chest radiographic findings: (a) stage 0 is a normal chest radiograph; (b) stage I, lymphadenopathy only; (c) stage II, lymphadenopathy and lung parenchymal disease; (d) stage III, parenchymal lung disease only; and (e) stage IV, pulmonary fibrosis.
At presentation, approximately 5-10% of patients have stage 0 disease; 50%, stage I; 25-30%, stage II; and 15%, stage III. Although most cases of sarcoidosis either regress or remain stable, 10-15% progress to pulmonary fibrosis. Generally, pulmonary function worsens with an increasing stage of disease, but radiologic staging does not correlate well with the severity of pulmonary function abnormalities. Often, the radiographic abnormalities appear worse than the degree of functional impairment actually present.
Extrapulmonary thoracic manifestations
Sarcoidosis predominantly affects the lungs, both clinically and radiologically. However, sarcoidosis can affect virtually any organ. Autopsy studies have shown cardiac involvement in 25% of cases, but symptoms and imaging findings occur in only 10% of patients with cardiac involvement. One half of patients with abnormal electrocardiographic results are asymptomatic.
Ventricular arrhythmias, heart block, congestive failure, angina, constrictive pericarditis, left ventricular aneurysm formation, and sudden cardiac death due to granulomatous inflammation of the cardiac conduction pathways have all been reported. Pericardial involvement is rare; when present, it usually occurs because of the direct extension of myocardial disease.
Frequency of organ involvement
The frequency of organ involvement varies considerably in different series. Rates may be as follows:
- Lung - 90%
- Lymph nodes - 75-90%
- Pleura - 1-5%
- Skin - 25%
- Eye - 25%
- Nasal mucosa - 20%
- Larynx - 5%
- Bone marrow - 15-40%
- Spleen -50-60%
- Liver -60-90%
- Kidney - Rare
- Calcium disorder - 1-2%
- CNS - 5%
- Bones - 5%
- Joints - 25-50%
- Heart - 5%
- Endocrine glands - Rare
- Parotid gland - 10%
- GI tract - Rare
Frequency
United States
In the United States, the prevalence of sarcoidosis is 5-40 cases per 100,000 population. However, it was not until the mid 1940s that a large number of cases were identified during mass chest radiography screening for the Armed Forces; before this, the high prevalence of sarcoidosis had not been recognized in North America. Sarcoidosis was once considered rare, but it is now the most common fibrotic lung disease; it occurs often enough in the United States for Congress to have declared a national Sarcoidosis Awareness Day in 1990.
Because sarcoidosis may mimic other diseases, its prevalence can only be estimated. About 5 in 100,000 white individuals in the United States have sarcoidosis. The disease occurs more frequently among African Americans, probably affecting 40 per 100,000 population.
Overall, the rate appears to be 20 cases per 100,000 population in cities on the East Coast; the rate is somewhat lower in rural locations. However, some investigators believe that these figures greatly underestimate the percentage of the US population with sarcoidosis.
International
Sarcoidosis occurs worldwide. The true prevalence of sarcoidosis is difficult to determine because the disease is often asymptomatic and frequently does not come to medical attention. Thoracic sarcoidosis is found with varying frequency in virtually every country of the world.
Sarcoidosis appears to be more common and more severe in certain geographic areas. Reports are subject to error because the surveillance and criteria for diagnosis vary from country to country.
The prevalence is higher in countries with temperate climates: In the United States, the incidence is 10-40 cases per 100,000 population; in the United Kingdom, 20-30 per 100,000; in Scandinavia, 64 per 100,000; and in Japan, 10-20 per 100,000. The overall incidence in Europe is 19 cases per 100,000 population; in Bulgaria, 1.4 per 100,000; in Spain, 0.04 per 100,000; and in Sweden, 64 per 100,000.
In tropical climes, the incidence is lower: In Africa, Southeast Asia, India, Central America, and South America, the incidence is less than 10 cases per 100,000 population.
Mortality/Morbidity
The overall mortality rate that is directly related to sarcoidosis is 5%. Patients may die from right-sided heart failure, respiratory failure, or massive hemoptysis. A small number of patients die from sudden cardiac death due to direct granulomatous involvement of the conduction pathways and myocardium.
Regarding morbidity, the 3 major complications of pulmonary sarcoidosis are mycetoma formation, fibrosis, and right-sided heart failure.
- Saprophytic fungal colonization, usually by Aspergillus species, occurs in more than 50% of patients with stage IV sarcoidosis and apical bullous disease. Although mycetomas may be clinically silent, hemoptysis is common. Life-threatening hemoptysis that requires surgical intervention or angiographic localization of bleeding with concurrent bronchial artery embolization occurs in a minority of patients.
- In general, sarcoidosis appears briefly and heals naturally in 60-70% of the cases, often without symptoms or the patient's knowledge. Approximately 20-30% of patients with sarcoidosis are left with chronic lung sequelae. In 10-15% of patients, sarcoidosis can become chronic.
- In 5-10% of patients, granulomas or fibrosis may seriously affect the function of vital structures, such as the lungs, heart, nervous system, liver, and kidneys. The consequences can be fatal.
Race
Sarcoidosis occurs in all races. Nevertheless, the risk is greater in young African American adults, especially women, and in those of Scandinavian, German, Irish, or Puerto Rican origin.
- In the US military, the prevalence among African Americans is 10-17 times that of whites. A genetic predisposition may be involved, but if so, the penetrance is weak because the frequency of occurrences in relatives is low. Approximately 20% of African American patients have an affected family member, whereas only 5% of white patients with sarcoidosis have a family member affected with sarcoidosis.
- Different races are also affected to varying degrees. Sarcoidosis is rarely seen in African or South American blacks. However, the prevalence in African Americans living in New York City (ie, 80 cases per 100,000 population) is 10 times higher than that in American whites. Extrathoracic manifestations of sarcoidosis also occur more frequently in black patients than in white patients.
- Racial characteristics also determine the ultimate prognosis. White patients are more likely to develop the milder form of the disease. In black individuals, sarcoidosis tends to have a more chronic and severe form.
Sex
Globally, a male-to-female ratio of approximately 2:1 is reported.
- In most countries, a slight female predominance is observed.
- In the United States, this female predominance has been noted only in the black population.
- Worldwide, white women are just as likely as white men to have sarcoidosis, but black women are twice as likely as black men to have sarcoidosis.
Age
Sarcoidosis mainly affects people aged 20-40 years, and the disease typically manifests in the third or fourth decade of life. However, the age range of patients extends from preadolescence to the seventh decade.
- A second peak occurs in women aged 45-65 years.
- Sarcoidosis rarely develops before the age of 10 years or after the age of 60 years.
- However, both symptomatic and asymptomatic sarcoidosis have been reported in younger and older people. When symptoms do appear, they are nonspecific and generally involve a feeling of ill health, tiredness, and cough.
Presentation
Clinical presentation
Usually, sarcoidosis occurs without symptoms. Although physical findings are normal, abnormalities are seen on the chest radiograph. Pulmonary dyspnea on exertion, cough (dry or productive), chest pain, and hemoptysis (rare) occur in 50% of cases. Approximately 50% of patients with sarcoidosis are asymptomatic at diagnosis; 25% complain of dyspnea and a persistent cough, which can be among the first symptoms of sarcoidosis; and 25% have extrathoracic symptoms, which are usually related to the skin or eyes. Constitutional symptoms, such as malaise weight loss, loss of appetite, and fever occur less commonly.2, 3, 4, 5
Löfgren syndrome
Löfgren syndrome is an acute form of sarcoidosis that occurs with an acute febrile illness accompanied by erythema nodosum; hilar lymphadenopathy; malaise; arthropathy; and, occasionally, uveitis and parotitis. Löfgren syndrome is common in Scandinavian patients; it is uncommon in African American and Japanese patients.
Skin involvement
Skin lesions, including those due to erythema nodosum or lupus pernio, and skin plaques or scars are found in around 30% of patients with sarcoidosis. Skin lesions can be subdivided into nonspecific types and specific types (which histologically reveal noncaseating granulomas).
Papular sarcoidosis is the most common specific skin lesion. These lesions are red or brown-to-purple skin papules; they are seen most commonly on the face or on extensive surfaces of the arm and legs (see Images 1 and 2). Papular rash is often associated with the acute form of sarcoidosis and, generally, a good prognosis.
Lupus pernio is a specific form of cutaneous sarcoidosis. It is characterized by indurated, bluish-purple elevations that mainly affect the nose and digits (see Image 3). Lupus pernio resembles lesions seen in acute cold injury (hence the name pernio). Lupus pernio is characteristically seen in African American individuals. The cosmetic effect of these skin lesions may prompt patients to seek medical attention. These lesions are frequently associated with serious systemic disease, including involvement of the upper respiratory tract, pulmonary fibrosis, chronic uveitis, and bone cysts.
Subcutaneous nodules are often a manifestation of chronic disease; however, they may appear any time in the course of disease. These nodules involve the limbs and trunk. The lesions are usually 0.5-2.0 cm in diameter, subcutaneous, firm, nontender, mobile, and red-brown to purple in color. They are generally not a prognostic indicator.
The plaques of cutaneous sarcoidosis are round or oval, annular or arciform, and red-brown to purple. These lesions usually affect the trunk and limbs. Plaques are frequently associated with persistent pulmonary involvement.
Preexisting, healed scars may become purple and indurated due to infiltration by sarcoid granulomas.
Erythema nodosum is characterized by erythematous nodules that are usually multiple, bilateral, and tender; they are mostly located on the anterior aspect of the lower limbs. These lesions are nonspecific manifestations of sarcoidosis. The prevalence of erythema nodosum varies widely in different parts of the world, affecting 10% of American patients or less and 30% of European patients. It has a predilection for female patients, particularly those of Scandinavian, Irish, or Puerto Rican origin. Erythema nodosum is often associated with arthropathy of the ankles, elbows, wrists, and hands. Erythema nodosum usually resolves, but other skin problems can persist.
Eye involvement
Approximately one quarter of patients with sarcoidosis have eye involvement at some time during the course of the disease. Eye disease is more common in children than in adults. Eye involvement may be asymptomatic, but 5% of patients with sarcoidosis present with eye symptoms.
Almost any part of the eye can be affected, including the eyelids, cornea, conjunctiva, uveal tract, sclera, retina, and lens. Symptomatic patients may present with conjunctival injection, photophobia, and unilaterally or bilaterally blurred vision. Rarely, cataracts, glaucoma, and blindness result. Lacrimal and salivary gland involvement may occur, even in the absence of ocular lesions. Slitlamp examination may reveal symptomatic, as well as asymptomatic, ocular involvement.
Involvement of other organs
Sarcoidosis may affect almost any organ of the body, but the lungs, skin, and eyes are most frequently involved. Besides the lungs and lymph nodes, structures more likely than others to be affected by sarcoidosis are the liver, skin, heart, nervous system, and kidneys, in decreasing order of frequency.
Patients may have symptoms related to the specific organ affected. Patients may be asymptomatic or have nonspecific constitutional symptoms. Symptoms may also vary with the chronicity of the disease, with the activity status of the disease, and with the extent of granulomatous involvement.
Heart failure due to cardiomyopathy is a rare occurrence.6 Heart block and sudden death may occur. Approximately 25% of patients have noncaseating granulomas within the heart at autopsy, but fewer than 5% have clinical cardiac disease (see Images 4-6).
An elevated alkaline phosphatase level suggests hepatic involvement. Although liver involvement is common, it rarely is clinically relevant.
Diagnostic evaluation
Biopsy
The diagnosis is established by obtaining biopsies of affected organs and by excluding other granulomatous conditions, such as fungal disease and TB, and other causes of lymphadenopathy, such as neoplasia. The central nervous system is affected in 1-5% of patients with sarcoidosis; this involvement can lead to neurologic problems.
Sarcoid granulomas can appear in the brain, spinal cord, and facial and optic nerves. Facial paralysis and other symptoms of nerve damage require prompt treatment. Other cranial nerve palsies and hypothalamic/pituitary dysfunction may occur. Lymphocytic meningitis is the most common neurologic manifestation.
Laboratory testing
Laboratory findings in sarcoidosis include leukopenia and hypercalcemia. Hypercalcemia and hypercalciuria are due to hydroxylation of 25-dihydroxy vitamin D in macrophages, which results in increased intestinal absorption of calcium. Persistent hypercalcemia can lead to nephrocalcinosis. Hypercalcemia is seen in about 10-13% of patients, whereas hypercalciuria is 3 times more common. However, the findings of leukopenia, hypercalcemia, and hypercalciuria are nonspecific.
Angiotensin-converting enzyme (ACE) is a product of macrophages and, therefore, an indicator of granuloma burden in the tissues. ACE levels are elevated in the serum and may be correlated with disease activity. The diagnostic value of elevated levels of ACE is limited by a 40% false-negative rate and a 10% false-positive rate. Its value lies in monitoring the response to treatment or the clinical course of the disease.
Immunologic testing
The immunologic imbalance in sarcoidosis may clinically manifest as impaired immunologic function. Cell-mediated immunity is enhanced at sites of disease activity, but it is depressed systemically. Patients may exhibit hypergammaglobulinemia caused by T-cell lymphokine stimulation of B lymphocytes.
The Kveim test involves an intradermal injection of a sodium chloride suspension of human sarcoid spleen or lymph nodes. Although the Kveim test is specific, it is limited by the unavailability of the antigen, a 4- to 6-week reaction time, and variability in the interpretation of results. The Kveim test is rarely used in the United States because the US Food and Drug Administration (FDA) has approved no antigen. However, a few hospitals and clinics may have some standardized test that has been privately prepared for their own use.
Pulmonary function testing
In sarcoidosis, abnormal pulmonary function test (PFT) results may be indistinguishable from those seen with other interstitial lung diseases. Such results include reduced lung volume, reduced diffusing capacity, and a normal or supranormal ratio of forced expiratory volume in 1 second to forced vital capacity. The extent of PFT abnormalities is related to the severity of lung involvement by granulomatous disease and fibrosis. In acute sarcoidosis, no functional impairment may be detectable; however, if the disease progresses, pulmonary physiologic findings may indicate restrictive and obstructive airway disease.
Low lung compliance results from diffuse interstitial disease. A generalized reduction in volume throughout all lobes and segments is reflected in decreased vital capacity, decreased residual volume, and decreased total lung capacity (restrictive lung disease). With endobronchial lesions or peribronchial fibrosis, PFTs may show a decreased flow rate caused by increased airway resistance (obstructive airway disease). Diffusion abnormalities may be assessed by performing the carbon monoxide diffusion capacity test. These are routinely used in evaluation and follow-up.
Cardiopulmonary exercise testing
Cardiopulmonary exercise testing can be used to assess the extent of pulmonary involvement. It is a sensitive test for identifying and quantifying the extent of disease. Results of cardiopulmonary exercise testing also may suggest cardiac involvement that otherwise is not evident.
Bronchoalveolar lavage is performed by means of bronchoscopy, which allows evaluation of the alveolar cell population. In healthy nonsmokers, more than 90% of alveolar cells found in the lavage fluid are macrophages, 9% are lymphocytes, and less than 1% are polymorphs. In a patient with sarcoidosis, the percentage of lymphocytes increases to 40%, whereas the percentage of macrophages decreases to 60%. The increased number of T lymphocytes is associated with an increase in the ratio of T-helper cells to T-suppressor cells. These findings are nonspecific and may also be found in drug-induced lung toxicity, pneumoconiosis, and amyloidosis.
In accordance with the position statement of the American Thoracic Society, all patients should undergo annual ECG testing. If patients report palpitations, they should undergo a through evaluation with at least a Holter monitor.
Disease progression
The progress of sarcoidosis is unpredictable, but certain clinical features may determine the ultimate prognosis. The sudden onset of systemic symptoms, such as weight loss and general malaise, usually indicates that the course of sarcoidosis is relatively short and mild. Dyspnea and, possibly, skin sarcoidosis often suggest that the sarcoidosis will be more chronic and severe.
Racial characteristics also determine the ultimate prognosis. White patients are more likely to develop the milder form of the disease. In black individuals, sarcoidosis tends to have a more chronic and severe form.
Differential diagnosis
The clinical manifestations of sarcoidosis are protean and may mimic different pathologies. Therefore, the differential diagnosis is wide and includes the following: (1) neoplasia, such as lymphoma and metastases (lymphangitis carcinomatosa); (2) TB and fungal infections; and (3) inflammation secondary to immune response, including idiopathic pulmonary fibrosis, hypersensitivity pneumonitis, berylliosis, silicosis, talcosis, asbestosis, and autoimmune diseases (eg, systemic lupus erythematosus, scleroderma, rheumatoid arthritis, ankylosing spondylitis).
Laboratory findings of leukopenia and hypercalcemia are nonspecific and have a wide differential diagnosis.
Related Medscape topics:
CME Systemic Lupus Erythematosus and Sjögren's Syndrome: Highlights From ACR 2007
CME Therapeutic Insight: Interactive Case Management of Lupus Nephritis
CME Rheumatoid Arthritis Questionnaire
Preferred Examination
When chest radiographic results are correlated with the clinical findings, chest radiography may be the only imaging required.7 Routine chest CT scanning is not usually indicated and adds little to patient care. Approximately 60-70% of patients with sarcoidosis have characteristic radiologic findings. In 25-30% of patients, the radiologic changes are nonspecific or atypical, and in 5-10% of patients, the chest radiograph is normal. Thus, approximately 30-40% of patients can benefit from a CT scan. CT is more sensitive than radiography in the detection of lymphadenopathy and subtle parenchymal disease. High-resolution CT (HRCT) is useful in differentiating active disease from fibrosis. HRCT results are well correlated with the yield of biopsy.
The accumulation of gallium-67 (67 Ga) is a sensitive but nonspecific indicator of active inflammation in patients with sarcoidosis. Gallium-67 avidity alone cannot be used to establish a diagnosis of sarcoidosis, and this finding has a limited correlation with the patient's clinical status. However,67 Ga scintigraphy is useful in identifying extrathoracic sites of involvement, in detecting active alveolitis, and in assessing response to treatment.8 Gallium-67 scans have low sensitivity and specificity as a diagnostic test; therefore, they are used infrequently. Gallium-67 scanning is useful in patients in whom the clinical picture remains confusing despite the presence of noncaseating granulomas in biopsy specimens, and it may useful in differentiating chronic hypersensitivity pneumonitis from sarcoidosis.9, 10, 11, 12, 13, 14, 15, 16, 17, 18
No large imaging studies are available to assess sarcoid cardiac involvement. Some have suggested a combined use of67 Ga and thallium scans. However, the number of studies that have reported on this technique have been small and subject to significant bias. Moreover, because of patchy sarcoid cardiac involvement, endomyocardial biopsy, which is regarded as a standard technique in the diagnosis, is subject to sampling error.19
Mycetomas may occur in more than 50% of patients with stage IV sarcoidosis and apical bullous disease. Although mycetomas may be clinically silent, hemoptysis is common. Life-threatening hemoptysis may be managed with the angiographic localization of bleeding and concurrent bronchial artery embolization in a minority of patients. Bronchial necrosis is more frequently encountered when absolute alcohol is used for embolization. The diagnosis is most confidently established when the clinicoradiologic findings are supported by histologic evidence of widespread noncaseating granulomas.
Limitations of Techniques
The limitation of all techniques is the nonspecificity of most methods of diagnostic imaging. A chest radiograph can be normal in biopsy-proven sarcoidosis. A false-positive diagnosis may occur with a variety of granulomatous diseases. Problems may also arise with the biopsy material.
CT is expensive both in terms of money and the radiation burden. Gallium-67 scanning is also limited by nonspecificity, and the scans may show normal uptake in established disease. Gallium-67 scanning is also time-consuming and expensive.
In a study in 31 patients, Okada et al performed a correlative analysis of longitudinal changes in bronchoalveolar lavage,67 Ga scanning, serum ACE activity, chest radiographic findings, and PFT results in pulmonary sarcoidosis.20 The investigators found that, in terms of the usefulness for estimating disease activity, differences in the 4 indicators were negligible. They concluded that a chest radiograph and serum angiotensin-converting enzyme (ACE) levels sufficiently reflect disease activity and that, at present, routine evaluation with67 Ga scanning and bronchoalveolar lavage is not necessarily indicated in the long-term management of patients with pulmonary sarcoidosis.
Differential Diagnoses
Other Problems to Be Considered
Neoplasia - Lymphoma and metastases (lymphangitis carcinomatosa)
Infections - TB and fungal
Inflammation secondary to immune response
Causes of noncaseating granulomas on biopsy
Berylliosis
TB
Leprosy
Fungal infections
Primary biliary cirrhosis
Hypersensitivity pneumonitis
Cat-scratch disease
Hilar infiltrates
TB
Bronchogenic carcinoma
Lymphoma
Fungal infections
| ||||||||||
References
Ma Y, Gal A, Koss MN. The pathology of pulmonary sarcoidosis: update. Semin Diagn Pathol. Aug 2007;24(3):150-61. [Medline].
Fernandes SR, Singsen BH, Hoffman GS. Sarcoidosis and systemic vasculitis. Semin Arthritis Rheum. Aug 2000;30(1):33-46. [Medline].
Gibbons WJ, Levy RD, Nava S, et al. Subclinical cardiac dysfunction in sarcoidosis. Chest. Jul 1991;100(1):44-50. [Medline].
Gotway MB, Tchao NK, Leung JW, et al. Sarcoidosis presenting as an enlarging solitary pulmonary nodule. J Thorac Imaging. Apr 2001;16(2):117-22. [Medline].
Reynolds HY. Sarcoidosis: impact of other illnesses on the presentation and management of multi-organ disease. Lung. 2002;180(5):281-99. [Medline].
Otsuka K, Terasaki F, Eishi Y, Shimomura H, Ogura Y, Horii T, et al. Cardiac sarcoidosis underlies idiopathic dilated cardiomyopathy: importance of mediastinal lymphadenopathy in differential diagnosis. Circ J. Dec 2007;71(12):1937-41. [Medline].
Clarke D, Mitchell AW, Dick R, James GD. The radiology of sarcoidosis. Sarcoidosis. Sep 1994;11(2):90-9. [Medline].
Diot P, Lemarie E, Baulieu JL, et al. Scintigraphy with J001 macrophage targeting glycolipopeptide. A new approach for sarcoidosis imaging. Chest. Sep 1992;102(3):670-6. [Medline].
Abe S. Clinical usefulness of 67Ga scintigraphy in pulmonary sarcoidosis. Nihon Kyobu Shikkan Gakkai Zasshi. Jan 1990;28(1):65-6. [Medline].
Bekerman C, Szidon JP, Pinsky S. The role of gallium-67 in the clinical evaluation of sarcoidosis. Semin Roentgenol. Oct 1985;20(4):400-9. [Medline].
Bourguet P, Delaval P, Herry JY. Direct quantitation of thoracic gallium-67 uptake in sarcoidosis. J Nucl Med. Oct 1986;27(10):1550-6. [Medline].
Kelly SJ, Wang KP. Transbronchial needle aspiration. J Thorac Imaging. Apr 1987;2(2):33-40. [Medline].
Lebtahi R, Crestani B, Belmatoug N, et al. Somatostatin receptor scintigraphy and gallium scintigraphy in patients with sarcoidosis. J Nucl Med. Jan 2001;42(1):21-6. [Medline].
Myslivecek M, Husak V, Kolek V, et al. Absolute quantitation of gallium-67 citrate accumulation in the lungs and its importance for the evaluation of disease activity in pulmonary sarcoidosis. Eur J Nucl Med. 1992;19(12):1016-22. [Medline].
Palestro CJ, Schultz B, Horowitz M, Swyer AJ. Indium-111-leukocyte and gallium-67 imaging in acute sarcoidosis: report of two patients. J Nucl Med. Nov 1992;33(11):2027-9. [Medline].
Rizzato G, Spinelli F, Tansini G, et al. Assessment of sarcoidosis activity by 67gallium lung scan. A study with follow-up. Respiration. 1983;44(5):360-7. [Medline].
Prager E, Wehrschuetz M, Bisail B, Woltsche M, Schwarz T, Lanz H, et al. Comparison of (18)F-FDG and (67)Ga-citrate in sarcoidosis imaging. Nuklearmedizin. 2008;47(1):18-23. [Medline].
Jonker GJ, Smulders NM, van Kroonenburgh MJ, Halders S, de Vries J, Faber CG, et al. Lung-uptake and -washout of MIBG in sarcoidosis. Respir Med. Jan 2008;102(1):64-70. [Medline].
Legmann P. Imaging and lung disease: uses and interpretation. Tuber Lung Dis. Jun 1993;74(3):147-58. [Medline].
Okada M, Takahashi H, Nukiwa T, et al. Correlative analysis of longitudinal changes in bronchoalveolar lavage, 67gallium scanning, serum angiotensin-converting enzyme activity, chest X-ray, and pulmonary function tests in pulmonary sarcoidosis. Jpn J Med. Aug 1987;26(3):360-7. [Medline].
Weinstein DS. Pulmonary sarcoidosis: calcified micronodular pattern simulating pulmonary alveolar microlithiasis. J Thorac Imaging. Jul 1999;14(3):218-20. [Medline].
Miller BH, Putman CE. The chest radiograph and sarcoidosis. Reevaluation of the chest radiograph in assessing activity of sarcoidosis: a preliminary communication. Sarcoidosis. Sep 1985;2(2):85-90. [Medline].
Bartz RR, Stern EJ. Airways obstruction in patients with sarcoidosis: expiratory CT scan findings. J Thorac Imaging. Oct 2000;15(4):285-9. [Medline].
Bergin C, Roggli V, Coblentz C, Chiles C. The secondary pulmonary lobule: normal and abnormal CT appearances. AJR Am J Roentgenol. Jul 1988;151(1):21-5. [Medline].
Hamper UM, Fishman EK, Khouri NF, et al. Typical and atypical CT manifestations of pulmonary sarcoidosis. J Comput Assist Tomogr. Nov-Dec 1986;10(6):928-36. [Medline].
Lynch DA, Webb WR, Gamsu G, et al. Computed tomography in pulmonary sarcoidosis. J Comput Assist Tomogr. May-Jun 1989;13(3):405-10. [Medline].
Nishimura K, Itoh H, Kitaichi M, et al. Pulmonary sarcoidosis: correlation of CT and histopathologic findings. Radiology. Oct 1993;189(1):105-9. [Medline].
Patil SN, Levin DL. Distribution of thoracic lymphadenopathy in sarcoidosis using computed tomography. J Thorac Imaging. Apr 1999;14(2):114-7. [Medline].
Brauner MW, Grenier P, Mompoint D, et al. Pulmonary sarcoidosis: evaluation with high-resolution CT. Radiology. Aug 1989;172(2):467-71. [Medline].
Chung MH, Edinburgh KJ, Webb EM, et al. Mixed infiltrative and obstructive disease on high-resolution CT: differential diagnosis and functional correlates in a consecutive series. J Thorac Imaging. Apr 2001;16(2):69-75. [Medline].
Muller NL, Kullnig P, Miller RR. The CT findings of pulmonary sarcoidosis: analysis of 25 patients. AJR Am J Roentgenol. Jun 1989;152(6):1179-82. [Medline].
Webb WR, Müller NL, Naidich DP, eds. High Resolution CT of the Lung. 1992: 76-87.
Johkoh T, Ikezoe J, Takeuchi N, et al. CT findings in "pseudoalveolar" sarcoidosis. J Comput Assist Tomogr. Nov-Dec 1992;16(6):904-7. [Medline].
Sider L, Horton ES Jr. Hilar and mediastinal adenopathy in sarcoidosis as detected by computed tomography. J Thorac Imaging. Apr 1990;5(2):77-80. [Medline].
Mendelson DS, Gray CE, Teirstein AS. Magnetic resonance findings in sarcoidosis of the thorax. Magn Reson Imaging. 1992;10(4):523-9. [Medline].
Craig DA, Colletti PM, Ratto D, et al. MRI findings in pulmonary sarcoidosis. Magn Reson Imaging. Sep-Oct 1988;6(5):567-73. [Medline].
Moore FG, Andermann F, Richardson J, et al. The role of MRI and nerve root biopsy in the diagnosis of neurosarcoidosis. Can J Neurol Sci. Nov 2001;28(4):349-53. [Medline].
Muller NL, Mayo JR, Zwirewich CV. Value of MR imaging in the evaluation of chronic infiltrative lung diseases: comparison with CT. AJR Am J Roentgenol. Jun 1992;158(6):1205-9. [Medline].
Cohen NP, Gosset J, Staron RB, Levine WN. Vertebral sarcoidosis of the spine in a football player. Am J Orthop. Dec 2001;30(12):875-7. [Medline].
Nakamura T, Sugihara H, Narihara R, et al. Antemortem diagnosis of cardiac sarcoidosis by abnormal uptake of 201Tl in bilateral hilar lymph nodes. Ann Nucl Med. Nov 1994;8(4):295-8. [Medline].
Gotway MB, Storto ML, Golden JA, et al. Incidental detection of thoracic sarcoidosis on whole-body 18fluorine-2- fluoro-2-deoxy-D-glucose positron emission tomography. J Thorac Imaging. Jul 2000;15(3):201-4. [Medline].
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. Oct 2006;23(3):201-8. [Medline].
Maier LA. Clinical approach to chronic beryllium disease and other nonpneumoconiotic interstitial lung diseases. J Thorac Imaging. Oct 2002;17(4):273-84. [Medline].
Sharma OP. Pulmonary sarcoidosis and corticosteroids. Am Rev Respir Dis. Jun 1993;147(6 Pt 1):1598-600. [Medline].
Hunninghake GW, Gilbert S, Pueringer R, et al. Outcome of the treatment for sarcoidosis. Am J Respir Crit Care Med. Apr 1994;149(4 Pt 1):893-8. [Medline].
Klech H, Kohn H, Huppmann M, Pohl W. Thoracic imaging with gallium-67. Eur J Nucl Med. 1987;13 Suppl:S24-36. [Medline].
Miller BH, Putman CE. The chest radiograph and sarcoidosis. Reevaluation of the chest radiograph in assessing activity of sarcoidosis: a preliminary communication. Sarcoidosis. Sep 1985;2(2):85-90. [Medline].
Further Reading
Keywords
Boeck sarcoid, Besnier-Boeck-Schaumann, lupus pernio, benign granulomatous sarcoid, Jungling's sarcoidosis, Jungling sarcoidosis, Mortimer's sarcoidosis, Mortimer sarcoidosis, Schaumann's sarcoidosis, Schaumann sarcoidosis, non-caseating granuloma, noncaseating granuloma
