Patients may have malaise, fever, and dyspnea of insidious onset. Symptoms from skin involvement (erythema nodosum, lupus pernio [Figure 9–6]), iritis, peripheral neuropathy, arthritis (Chapter 20), or cardiomyopathy may also cause the patient to seek care. Some individuals are asymptomatic and come to medical attention after abnormal findings (typically bilateral hilar and right paratracheal lymphadenopathy) on chest radiographs. Physical findings are atypical of interstitial lung disease in that crackles are uncommon on chest examination. Other symptoms and findings may include parotid gland enlargement, hepatosplenomegaly, and lymphadenopathy.
Skin involvement in sarcoidosis (lupus pernio), here involving the nasal rim. (Used, with permission, from Richard P. Usatine, MD, in Usatine RP, Smith MA, Mayeaux EJ Jr, Chumley H, Tysinger J. The Color Atlas of Family Medicine. McGraw-Hill, 2009.)
Laboratory tests may show leukopenia, an elevated erythrocyte sedimentation rate, and hypercalcemia (about 5% of patients) or hypercalciuria (20%). Angiotensin-converting enzyme (ACE) levels are elevated in 40–80% of patients with active disease. This finding is neither sensitive nor specific enough to have diagnostic significance. Physiologic testing may reveal evidence of airflow obstruction, but restrictive changes with decreased lung volumes and diffusing capacity are more common. Skin test anergy is present in 70%. ECG may show conduction disturbances and dysrhythmias.
Radiographic findings are variable and include bilateral hilar adenopathy alone (radiographic stage I), hilar adenopathy and parenchymal involvement (radiographic stage II), or parenchymal involvement alone (radiographic stage III). Parenchymal involvement is usually manifested radiographically by diffuse reticular infiltrates, but focal infiltrates, acinar shadows, nodules, and, rarely, cavitation may be seen. Pleural effusion is noted in less than 10% of patients. Stage IV disease refers to advanced fibrotic changes principally in the upper lobes.
The diagnosis of sarcoidosis generally requires histologic demonstration of noncaseating granulomas in biopsies from a patient with other typical associated manifestations. Other granulomatous diseases (eg, berylliosis, tuberculosis, fungal infections) and lymphoma must be excluded. Biopsy of easily accessible sites (eg, palpable lymph nodes, skin lesions, or salivary glands) is likely to be positive. Transbronchial lung biopsy has a high yield (75–90%) as well, especially in patients with radiographic evidence of parenchymal involvement. Some clinicians believe that tissue biopsy is not necessary when stage I radiographic findings are detected in a clinical situation that strongly favors the diagnosis of sarcoidosis (eg, a young black woman with erythema nodosum). Biopsy is essential whenever clinical and radiographic findings suggest the possibility of an alternative diagnosis, such as lymphoma. BAL fluid in sarcoidosis is usually characterized by an increase in lymphocytes and a high CD4/CD8 cell ratio. BAL does not establish a diagnosis but may be useful in following the activity of sarcoidosis in selected patients. All patients require a complete ophthalmologic evaluation.