pulmonary disorders
Sarcoidosis
Diagnosis of Sarcoidosis
Chest imaging Biopsy Exclusion of other granulomatous disorders Sarcoidosis is most often suspected when hilar adenopathy, with or without lung infiltrates, is incidentally detected on chest x-ray. Bilateral hilar adenopathy is the most common abnormality. If sarcoidosis is suspected, a chest x-ray should be the first test if it has not already been done. The x-ray appearance tends to roughly predict the likelihood of spontaneous remission (see table Chest X-ray Staging of Sarcoidosis ) in patients with only thoracic lymph node involvement. However, staging sarcoidosis by chest x-ray can be misleading; for example, extrapulmonary sarcoidosis, such as A normal chest x-ray (stage 0) does not exclude the diagnosis of sarcoidosis, particularly when cardiac or neurologic involvement is suspected. A high-resolution CT is more sensitive for detecting hilar and mediastinal lymphadenopathy and parenchymal abnormalities. Lung parenchymal involvement is predominantly in the upper lobes but can be in any part of lungs. CT findings (see also image) in more advanced stages (II to IV) include the following: Thickening of the bronchovascular bundles and bronchial walls Beading of the interlobular septa Ground-glass opacification Parenchymal nodules, cysts, or cavities Traction bronchiectasis Bilateral hilar adenopathy in stage I sarcoidosis. By permission of the publisher. From Tanoue L, Elias J. InBone's Atlas of Pulmonary and Critical Care Medicine. Edited by J Crapo. Philadelphia, Current Medicine, 2005. Bilateral hilar adenopathy with interstitial opacities in stage II sarcoidosis. By permission of the publisher. From Tanoue L, Elias J. InBone's Atlas of Pulmonary and Critical Care Medicine. Edited by J Crapo. Philadelphia, Current Medicine, 2005. Diffuse interstitial opacities without hilar adenopathy in stage III sarcoidosis. By permission of the publisher. From Tanoue L, Elias J. InBone's Atlas of Pulmonary and Critical Care Medicine. Edited by J Crapo. Philadelphia, Current Medicine, 2005. Severe, diffuse fibrosis with hilar adenopathy and cystic changes of the upper lobes in stage IV sarcoidosis. By permission of the publisher. From: Tanoue L, Elias J. InBone's Atlas of Pulmonary and Critical Care Medicine. Edited by J Crapo. Philadelphia, Current Medicine, 2005. This high-resolution CT of the chest of a patient with pulmonary sarcoidosis shows thickening of the bronchovascular bundles and beading of the interlobular septa. Image courtesy of Birendra P. Sah, MD, FCCP. When imaging suggests sarcoidosis, the diagnosis is confirmed by demonstration of noncaseating granulomas on biopsy and exclusion of alternative causes of granulomatous disease (see table Differential Diagnosis of Sarcoidosis ). Löfgren syndrome does not require confirmation by biopsy. The diagnostic evaluation, therefore, requires the following: Selection of a biopsy site Exclusion of other causes of granulomatous disease Assessment of the severity and extent of disease to determine whether therapy is indicated Appropriate biopsy sites may be obvious from physical examination and initial assessment; peripheral lymph nodes, skin lesions, and conjunctivae are all easily accessible. Endobronchial ultrasound–guided transbronchial needle aspiration (EBUS-TBNA) of a mediastinal or hilar lymph node has a reported diagnostic yield of about 90% and is the diagnostic procedure of choice in patients with intrathoracic involvement. When pulmonary sarcoidosis is suspected and EBUS-TBNA is nondiagnostic, bronchoscopic transbronchial lung biopsy with bronchoalveolar lavage (BAL) can be used. It can also be used in patients without any lung parenchymal infiltrates because diagnostic yield for transbronchial lung biopsy in stage I sarcoidosis is about 50%. If the bronchoscopic transbronchial biopsy is nondiagnostic, it can be tried a second time. If EBUS-TBNA and bronchoscopic transbronchial biopsies are nondiagnostic or if bronchoscopy cannot be tolerated, mediastinoscopy can be done to biopsy mediastinal or hilar lymph nodes, or video-assisted thoracoscopic (VAT) lung biopsy or open-lung biopsy can be done to obtain lung tissue. If sarcoidosis is strongly suspected but a biopsy site is not evident based on examination or imaging findings, positron emission tomography (PET) scanning can help identify occult active sites such as heart, bone, muscle, and brain. Exclusion of other diagnoses is critical, especially when symptoms and x-ray signs are minimal, because many other disorders and processes can cause granulomatous inflammation (see table Differential Diagnosis of Sarcoidosis ). Biopsy tissue should be cultured for fungi and mycobacteria. Exposure history to occupational (eg, silica, beryllium), environmental (eg, moldy hay, birds, and other antigenic triggers of Severity is assessed according to organ involvement so, for example, with only pulmonary involvement Pulmonary function tests Overview of Tests of Pulmonary Function results are often normal in early stages but demonstrate restriction and reduced diffusing capacity for carbon monoxide (DLCO) in advanced disease. Airflow obstruction also occurs and may suggest involvement of the bronchial mucosae. Adding a 6-minute walk test may characterize functional impairment more comprehensively than the results of pulmonary function tests alone. Patients with extensive lung involvement may have normal oxygen saturation at rest but may show desaturation with exertion. Recommended routine screening tests for extrapulmonary diseaseinclude 12- lead ECG, Holter monitoring, and echocardiography Slit-lamp ophthalmologic examination Routine blood tests to evaluate renal and hepatic function Serum calcium levels and 24-hour urinary calcium excretion Imagingis often needed to detect extrapulmonary sarcoidosis. Cardiac magnetic resonance imaging (MRI) with and without gadolinium contrast may be appropriate in patients with cardiac symptoms. In patients with neurologic symptoms, brain or spine MRI with or without gadolinium may be needed. Bone scans and electromyography may be appropriate in patients with rheumatologic symptoms. PET scanning appears to be the most sensitive test for detecting bone and other extrapulmonary sarcoidosis and is used together with MRI in patients with cardiac involvement. Abdominal CT with radiopaque contrast agents is not routinely recommended but can provide evidence of hepatic or splenic involvement (eg, enlargement, hypolucent lesions). Whole-body gallium scanning has been largely replaced by PET scanning. If available, gallium scanning may provide useful supportive evidence in the absence of tissue confirmation. Symmetric increased uptake in mediastinal and hilar nodes (lambda sign) and in lacrimal, parotid, and salivary glands (panda sign) strongly suggest sarcoidosis. A negative result in patients takingprednisoneis unreliable. nitrogen (BUN), creatinine, and liver test results may be elevated in renal and hepatic sarcoidosis. Total protein may be elevated because of hypergammaglobulinemia. Elevated erythrocyte sedimentation rate is common but nonspecific. Measurement of calcium in a urine specimen collected over 24 hours is recommended to exclude hypercalciuria, even in patients with normal serum calcium levels. Elevated serum angiotensin-converting enzyme (ACE) levels can suggest sarcoidosis but are nonspecific and may be elevated in patients with other conditions (eg, Hyperthyroidism , should be done along with bronchoscopic biopsy to rule out suspected infections (eg, when findings with less invasive means such as imaging are not typical of sarcoidosis) and to exclude other forms of Overview of Interstitial Lung Disease if the diagnosis of sarcoidosis is in doubt. The findings on BAL vary considerably, but lymphocytosis (lymphocytes 