CARDIAC MANIFESTATIONS.

Pericardial disease is the most common cardiac feature of RA. Evidence of pericardial involvement with old fibrinous lesions is found in approximately 40% of patients at autopsy. A similar frequency of pericardial abnormalities can be detected by echocardiography in asymptomatic RA patients. Clinically evident pericarditis in RA, however, is infrequent. Large pericardial effusions with cardiac tamponade and death are rare. Constrictive pericarditis is somewhat more common and is typically manifested as dyspnea, right-sided heart failure, and peripheral edema. Pericardial fluid characteristics include a low glucose concentration, increased level of lactate dehydrogenase, elevated immunoglobulin levels, and low complement activity.

Rheumatoid nodules may occasionally develop in the myocardium or heart valves, and vasculitis may involve the coronary arteries. Conduction abnormalities, valvular incompetence or stenosis, and myocardial infarction are all rare clinical sequelae of rheumatoid heart disease.

PULMONARY MANIFESTATIONS.

Rheumatoid pleural disease, although frequently found at autopsy, is most commonly asymptomatic. Occasionally a pleural effusion may cause respiratory limitation. Neoplasm and infection should be ruled out by a pleural tap. Typically the pleural fluid is exudative, and white cell counts vary greatly but are generally less than 5000 per microliter. Glucose levels tend to be low, and the lactate dehydrogenase level is high. Total hemolytic complement, C3, and C4 levels are low. Immune complexes and rheumatoid factor are frequently found in the pleural fluid.

Intrapulmonary nodules may also be seen (Fig. 286-8) . Although usually asymptomatic, they may become infected and cavitate or rupture into the pleural space and produce a pneumothorax. Malignancy must be excluded in an RA patient with a solitary lung nodule, as in any other patient. Similar but distinct nodular infiltrates may also be seen in rheumatoid lungs in association with pneumoconiosis (Caplan's syndrome).

Finally, a diffuse interstitial fibrosis with pneumonitis may progress to a honeycomb appearance on the radiograph, bronchiectasis, chronic cough, and progressive dyspnea. Pulmonary function tests show diminished compliance and a restrictive ventilatory pattern. Large airways are not involved. An irreversible combination of respiratory insufficiency and resultant right-sided cardiac failure is possible. Rarely, small airway obstruction may develop into a necrotizing bronchiolitis. This complication also may result from treatment with gold and D-penicillamine.

NEUROLOGIC MANIFESTATIONS.

Peripheral neuropathies can be produced by proliferating synovium causing compression of nerves. Carpal tunnel syndrome (median neuropathy) (see under Articular Manifestations) is common, and a similar entrapment of the anterior tibial nerve (tarsal tunnel syndrome) can result in paresthesias with footdrop. Rheumatoid vasculitis may cause a mononeuritis multiplex condition with patchy sensory loss in one or more extremities, often in association with wristdrop or footdrop. Cervical myelopathy can result from atlantoaxial subluxation (see under Articular Manifestations). The central nervous system is usually spared, although cerebral vasculitis and rheumatoid nodules in the meninges have been described.

OPHTHALMOLOGIC MANIFESTATIONS.

Sjogren's syndrome is the most frequent ocular complication and may cause corneal damage associated with dryness of the eyes. Xerostomia and/or parotid gland enlargement may accompany ocular dryness. Episcleritis is a self-limited condition associated with redness of the eye and only mild pain. Scleritis is more painful and may result in visual impairment. If this condition progresses to thinning of the tissue allowing the dark blue color of the choroid below to show through, it is termed "scleromalacia perforans." The histologic picture is similar to that of a rheumatoid nodule.

FELTY'S SYNDROME.

This triad of chronic RA, splenomegaly, and neutropenia is often accompanied by lymphadenopathy, hepatomegaly, fever, weight loss, anemia, and thrombocytopenia. Hyperpigmentation and leg ulcers may also occur. The syndrome typically appears late in the course of a seropositive, destructive arthritis, often after joint disease is believed to be "burnt out." Recurrent infections with gram-positive organisms constitute the most serious clinical problems and do not correlate with the severity of neutropenia. The bone marrow is typically hyperplastic. Hypersplenism and immune-mediated destruction of white blood cells are believed to cause the neutropenia. Splenectomy may correct the neutropenia and prevent further infections in some patients, but many do not improve. The "large granular lymphocyte syndrome," which is probably a pre-malignant disorder of T lymphocytes, may mimic Felty's syndrome in RA patients. Splenectomy should not be performed for this disorder because it may hasten the onset of malignancy.

LABORATORY FEATURES.

A chronic normocytic, normochromic anemia with hematocrit values from 30 to 35% is usual. Typically, both serum iron levels and iron-binding capacity are low. The anemia does not respond to administration of iron, but erythropoietin may be effective when the anemia is severe. The white blood cell count and differential are typically normal, but eosinophilia may occur in severe systemic disease. The platelet count may be moderately elevated because of chronic inflammation. The erythrocyte sedimentation rate is elevated in most patients but only roughly parallels disease activity. The presence of rheumatoid factor is detected in more than 80% of cases and is useful in clinical diagnosis. Antinuclear antibodies detected by immunofluorescence, usually in low titer, can be found in 30 to 40% of cases. DNA typing of RA-associated HLA-DRB1 alleles (DR4, DR1, others; see Table 286-2) has no diagnostic utility because these genes occur in high frequencies in the normal population. However, detection of patients homozygous for these DRB1 "susceptibility/severity" alleles early in disease may predict the worst prognosis, in which case early, aggressive therapy is indicated.

Synovial fluid analysis usually shows a poor mucin clot test and white cell counts in the range of 5000 to 20,000 per cubic millimeter, with 50 to 70% as polymorphonuclear leukocytes (Table 286-4) . The synovial fluid glucose concentration is usually normal, but very low values occur occasionally, even in the absence of a superimposed infectious arthritis. Complement levels are typically low.