Page 1014 - Clinical Immunology_ Principles and Practice ( PDFDrive )

978 Part Seven Organ-Specific Inflammatory Disease

are difficult to differentiate from the primary pleuropulmonary occupational dust exposures have also been associated with this
manifestations of the disease. syndrome.
Pleuritis and Pleural Effusions Airway Disease
As in SLE, pleural abnormalities are one of the most common Airflow limitation is a common finding in patients with RA, being
pulmonary complications of RA. Pleural effusion is clinically present in approximately one-third of patients. The mechanism(s)
evident in approximately 5% of patients, and this can occur responsible for airway disease is poorly understood. The interplay
before the development of arthritis. Pleural disease is often of cigarette smoking and RA may play a role.
discovered as an incidental finding on routine chest radiography, A life-threatening complication of RA is upper airway
but nonspecific chest pain, dyspnea, and fever are not unusual. obstruction, resulting from synovitis of the cricoarytenoid joint.
The effusion can be unilateral or bilateral and can coexist with Common presenting complaints include a sore throat, hoarseness,
ILD. and fullness in the throat. It can progress to inspiratory stridor
Typically, the effusion is an exudate, with a glucose level less and upper airway obstruction. This complication occurs more
than 30 mg/mL in 70–80% of cases. The mechanism underlying commonly in women, particularly in those with advanced RA.
the low pleural fluid glucose is impaired membrane transport Seventy-five percent of patients were found to have cricoarytenoid
of glucose. A low pleural fluid pH is thought to occur secondary abnormalities when screening with direct or indirect laryngoscopy
to impaired carbon dioxide exit from the pleural space. If the and computed tomography (CT) was utilized. The treatment of
effusion is chronic, the cholesterol concentration can be increased, cricoarytenoid arthritis includes antiinflammatory medications.
and the pleural fluid can have a milky appearance (pseudochy- Bronchiolitis obliterans is a progressive form of obstructive
lothorax). Cytological examination reveals multinucleated giant lung disease that is being increasingly recognized as a complication
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cells, spindle-shaped macrophages, and necrotic debris. of RA. This entity was thought to develop secondary to the
Most rheumatoid effusions are small and asymptomatic, thus use of penicillamine in the treatment of RA, but most cases
requiring no treatment. They resolve over several months without occur in the absence of this therapy. The histopathological lesion
complications. The use of glucocorticoids for active articular of bronchiolitis obliterans is constrictive bronchiolitis, which is
disease hastens the resolution of the pleural process. characterized by concentric submucosal and peribronchiolar
fibrosis resulting in extrinsic compression and obliteration of
the bronchiolar lumen. The typical clinical presentation is insidi-
CLInICaL PearLS ous onset of cough and dyspnea, with a normal or hyperinflated
Lung Involvement in Rheumatoid Arthritis (RA) chest on radiography. This complication occurs more commonly
in women than in men. Pulmonary function studies show airflow
• RA is more common in women, but pleuropulmonary complications limitation with hyperinflation and a reduced diffusing capacity.
occur more frequently in men. Expiratory HRCT shows multiple areas of air trapping (mosaic
• Factors associated with pleuropulmonary complications of RA include pattern). Some individuals respond to high-dose glucocorticoids
more severe articular involvement, subcutaneous nodules, and high
levels of rheumatoid factor. and cytotoxic drugs, but in most patients, bronchiolitis obliterans
• Pleural effusions are the most common complication, characterized progresses to respiratory failure.
by an exudate and a low glucose and low pH. Bronchiectasis occurs at an increased frequency in RA, usually
• The differentiation of rheumatoid nodules from malignant lesions can in individuals with long-standing articular disease. Productive
be difficult. cough and dyspnea are the most common respiratory symptoms.
• The rapid growth of a nodule should prompt aggressive investigation In most patients, bronchiectasis is not clinically significant.
for a malignant cause.
Recurrent pneumonia and respiratory failure are potentially fatal
complications of this problem.

Rheumatoid Nodules Interstitial Lung Disease
Rheumatoid or necrobiotic nodules are the only pleuropulmonary Although ILD is a common complication of RA, the incidence is
manifestation specific for RA. These nodules are most commonly difficult to determine, since different methods of detection have
seen in men with active articular disease, high rheumatoid factor been employed and dissimilar populations of patients have been
titers, and subcutaneous nodules. Most individuals are asymp- studied. However, clinically significant ILD occurs in approxi-
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tomatic and are diagnosed on routine chest radiography. mately 14% of patients. The development of ILD in relation
Radiographically, these nodules can be singular or multiple with to the onset of arthritis is variable. Most often, the ILD develops
an upper to midlung zone predominance. Cavitation occurs in subsequent to arthritis, but in approximately 20% of patients,
approximately 50% of cases. HRCT indicates a higher frequency the lung disease precedes the onset of arthritis and is associated
of nodules than previously thought. Rarely, subpleural necrobiotic with cigarette smoking, presence of the shared HLA-DR4 epitope,
nodules can erode into the pleural space, resulting in a pneu- and RA-specific anticitrullinated protein antibodies.
mothorax with a complicating bronchopleural fistula. It can be The most common histopathologies identified in this patient
difficult to differentiate these nodules from malignant lesions, population are UIP, LIP, NSIP and BOOP. The clinical manifesta-
and open-lung biopsy is frequently necessary. Evidence of rapid tions of ILD in RA resemble those seen in idiopathic disease
growth on chest radiography should prompt an aggressive and include a dry, nonproductive cough and dyspnea on exertion.
diagnostic evaluation. Chest radiography and HRCT show increased reticular markings
Caplan syndrome refers to the rapid development of pulmonary with a predilection for the peripheral lower lung zones. Often,
nodules predominantly in the upper lung zone. This syndrome pleural abnormalities accompany the interstitial changes. With
was originally described in Welsh coalminers with RA. Histologi- advanced disease, progression to honeycomb lung occurs. LIP
cally, these nodules are identical to necrobiotic nodules. Other usually occurs in cases of RA complicated by Sjögren syndrome;