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New Treatments for Sarcoidosis
Sarcoidosis is a multisystem disease of unknown etiology that is characterized by the presence of noncaseating granulomas in various tissues. Any organ
system may be affected. Most patients are asymptomatic and come to medical attention because of unrelated respiratory symptoms. Most of
those asymptomatic patients are recognized through a chest radiograph abnormality. Fewer than 5% of patients who have
sarcoidosis have a normal chest radiograph. Furthermore, the morbidity and mortality that are associated with sarcoidosis result most often from pulmonary
involvement. Sarcoidosis is primarily a respiratory tract disorder that may also have features of extrapulmonary disease.
Many infectious and noninfectious conditions are associated with granuloma formation and a histopathologic picture indistinguishable from that of
sarcoidosis. Thus, diagnosis of sarcoidoses requires the exclusion of other causes of granuloma formation. Berylliosis and histoplasmosis, for example,
can have clinicopathologic features identical to those of sarcoidosis.
Epidemiology
Sarcoidosis occurs worldwide among all ethnic groups, but there are striking regional and ethnic differences in its incidence and prevalence.
For example, in the United States, sarcoidosis is 10 times more common among blacks than among whites and tends to be more
severe in black patients. However, this increased prevalence is not observed among blacks.
Pathogenesis
A specific sequence of events leads to granuloma formation in sarcoidosis. Expansion of the helper T cell population in the lungs likely
occurs through the activation of T cells by macrophages via interleuken-1 (IL-1) and the subsequent release of
IL-2 (also termed T cell growth factor) by the helper T cell. IL-2 causes self-replication of the existing T cell population.
This population of helper T cells, which are greatly increased in number and in degree of activity, recruits monocytes from peripheral blood into the lung by
Clinical Manifestations of Intrathoracic Sarcoidosis
The most common manifestations of intrathoracic sarcoidosis are bilateral hilar lymphadenopathy and diffuse infiltrative lung disease.
A staging system has been created on the basis of the presence or absence of these two manifestations on radiography: stage I,
bilateral hilar lymphadenopathy alone; stage II, bilateral hilar lymphadenopathy and diffuse infiltrative lung disease; and stage III, diffuse infiltrative
lung disease alone.
Symptoms resulting from parenchymal lung involvement include dyspnea and cough. Pulmonary function abnormalities are found in nearly all symptomatic
patients and in some patients who are asymptomatic. Physiologic abnormalities in patients with symptomatic sarcoidosis typically consist of a reduction in
Dlco and vital capacity without airflow obstruction. The Dlco typically becomes abnormal before the vital capacity, but both
measurements are usually affected in persons with moderate to severe symptoms. Airflow obstruction is relatively uncommon, except in patients with
advanced disease or with endobronchial involvement of larger airways. In rare instances, diffuse endobronchial
granulomas in small airways lead to a predominantly obstructive abnormality in patients who present with stage I disease.
Most patients with stage I sarcoidosis are asymptomatic, and the abnormality is detected on a routine chest radiograph. When stage I disease is symptomatic,
the symptoms are nonpulmonary in nature and consist of systemic complaints of fever, malaise, arthralgia, or erythema nodosum. The presence of fever,
bilateral hilar lymphadenopathy, arthralgia or arthritis, and erythema nodosum is known as Löfgren’s syndrome. Approximately 10% of
The frequency of symptoms is higher in patients with stage II sarcoidosis, but asymptomatic cases are not unusual. Symptoms may be primarily systemic,
as in stage I disease, or may arise from pulmonary involvement. A presentation of extensive radiographic abnormalities associated with only minimal respiratory
symptoms is not uncommon. Roughly 50% of patients with stage II sarcoidosis will be in remission 2 years after presentation. Stage
II disease is more likely to be progressive and to follow a chronic symptomatic course than stage I disease.
Stage III disease is found at presentation in 5% to 15% of patients. Respiratory symptoms are common, but as in stage II disease
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