PULMONARY MANIFESTATIONS.

Pulmonary involvement occurs in most patients and is manifested as pleurisy, coughing, dyspnea, abnormal pulmonary function tests, or chest radiographic abnormalities. Pleurisy occurs in over 50% of patients; the most common cause is chest wall pain on local pressure and/or movement. Pleuritis (inflammation of the pleura) also causes pleurisy. It is diagnosed by the presence of a pleural friction rub and/or the radiographic presence of a pleural effusion. Effusions typically have low complement and protein levels, few WBCs (the pleura has mononuclear cells), glucose levels approximating plasma levels (by contrast, they are low in rheumatoid arthritis), and LE cells. Cough usually represents an infection, but pulmonary edema secondary to cardiac or renal failure or fluid overload in a patient receiving corticosteroids should be considered.

Acute lupus pneumonitis occurs in 5 to 12% and is characterized by fever, cough (even hemoptysis), pleurisy, and dyspnea. Radiography shows diffuse acinar infiltrates, especially in the lower lobes. Subsequently, interstitial infiltrates and fibrosis may develop, with pulmonary function abnormalities. The prognosis is poor.

Pulmonary hypertension may complicate SLE but is more frequent with scleroderma or mixed connective tissue disease. Raynaud's phenomenon is common. Late findings include dyspnea, hypoxemia, restricting lung disease, and reduced CO₂diffusing capacity.

The shrinking or vanishing lung syndrome has been described in some patients. It is believed to result from weakening and elevation of the diaphragm (lung fields are radiographically clear).

CARDIOVASCULAR MANIFESTATIONS.

Pericardial effusion is observed by echocardiography in most patients, and clinical pericarditis, manifested as substernal chest pain, a pericardial rub, and electrocardiographic (ECG) changes, has been noted in up to 48% of patients. Tamponade and restrictive pericarditis are rare. The fluid has characteristics similar to SLE pleural fluids.

Myocarditis, characterized by resting tachycardia, arrhythmias, ECG non-specific ST-T wave abnormalities, and unexplained cardiomegaly with congestive heart failure, has been noted in 8 to 78% of large series.

Coronary artery disease is being recognized increasingly, particularly in patients with long-standing disease, especially those receiving chronic corticosteroids. As a result, a greater number of younger patients with angina, myocardial infarctions, and congestive heart failure are being seen. The cause of the premature atherosclerosis remains unclear, but steroid-induced lipid abnormalities, immune complex deposition along blood vessels, and hypertension may all play a role. Hypertension is common, especially with flares of nephritis, chronic renal disease, and steroid use.

Valvular disease has been noted in up to 25% of patients; most common is mitral valve prolapse. Murmurs are even more common and may represent valvular disease or be due to anemia, fever, and/or cardiomegaly. Echocardiography is very useful to detect Libman-Sacks verrucous endocarditis. Verrucae are typically near the edge of the valve. Bacterial endocarditis may develop on damaged valves.

Thrombophlebitis occurs in more than 10% of patients with SLE. It most commonly affects the lower part of the leg and is often associated with antiphospholipid antibodies and oral contraceptives. The renal veins and inferior vena cava are rarely involved, but their involvement may cause nephrotic syndrome; pulmonary embolisms are uncommon.

HEMATOLOGIC CONSIDERATIONS.

Abnormalities of the formed elements of blood and the clotting and fibrinolytic systems are common. Anemia occurs in at least 50% of patients. The most common cause is chronic disease; RBCs are normochromic and normocytic, the reticulocyte count is low, and iron stores are adequate. Anemia may reflect chronic gastrointestinal blood loss secondary to the use of non-steroidal anti-inflammatory drugs (NSAIDs) and/or steroids--or secondary to excessive menstrual bleeding. Hemolytic anemia frequently occurs, and the reticulocyte count is elevated, haptoglobin levels are low, and the Coombs' test is positive. A positive Coombs' test with both immunoglobulin and complement on RBCs is associated with hemolysis, whereas a positive complement Coombs' test and no other findings rarely features hemolysis. Antibodies are usually anti-Rh and are "warm." Medications, especially immunosuppressives, may induce anemia--here, reticulocyte counts will be low and haptoglobin levels normal.

Leukopenia with a WBC count under 4500 has been noted in over 50% of patients, whereas counts under 4000 occur in only 17%. Granulocytes are affected more than lymphocytes. Leukopenia usually results from immune mechanisms (i.e., antineutrophil antibodies, immune complexes) or medications. Lymphocytopenia (which may be due to complement-fixing IgM or cold-reactive antibodies) may occur during active disease. Leukocytosis, or an excess of neutrophils, generally reflects infection or steroid use. An increase in activated T cells and a decrease in natural killer cells are noted, especially during active disease.

Thrombocytopenia with platelet counts under 150,000 per cubic millimeter has been noted in over 50% of patients, whereas counts under 50,000 have been noted in only 10%. Thrombocytopenia may reflect myeloproliferative diseases, ineffective thrombopoiesis (e.g., megaloblastic anemia), abnormal platelet distribution (e.g., splenomegaly), and abnormal immune mechanisms (antiplatelet antibodies, disseminated intravascular coagulation, and idiopathic thrombocytopenic purpura [ITP]). ITP may be the first manifestation of SLE. Most patients with both hemolytic anemia and ITP (Evans' syndrome) have SLE. In SLE-associated ITP, platelets are sensitized by IgG antibodies, which then bind to (splenic) macrophage Fc receptors with resulting phagocytosis--thrombocytopenia ensues when production fails to keep up with accelerated destruction. Platelet counts under 50,000 may rarely cause symptomatic bleeding, whereas counts under 20,000 per cubic millimeter may cause petechiae, purpura, nosebleeds, and gum bleeding.

Lymphadenopathy occurs in 50% of patients, especially during active disease. Nodes are typically small, soft, non-tender, and discrete in the neck, axillary, and inguinal areas. Biopsies may reveal follicular hyperplasia. Infection and malignancy should always be considered. When in doubt, a biopsy should be done.

Splenomegaly occurs in 10 to 20% of patients, especially during active disease and in association with lymphadenopathy. Splenomegaly does not necessarily cause hemolytic anemia but is usually associated with leukopenia. A slight increase in lymphoproliferative malignancies is observed in patients with SLE.

Antibodies to many clotting factors have been described in patients with SLE, including Factors VIII, IX, XI, XII, and XIII. These antibodies may induce bleeding. Antiphospholipid antibodies are found in about 25% of patients with SLE (seeChapter 187). They should be suspected when the patient has a prolonged partial thromboplastin time, arterial and venous thromboses, thrombocytopenia, false-positive tests for syphilis, or recurrent midtrimester miscarriages. Weaker associations have been noted with livedo reticularis, renal disease, pulmonary hypertension, and cardiac valvular disease. Some individuals with antiphospholipid antibodies do not have SLE. Antiphospholipid antibodies can be detected as a lupus anticoagulant and as anticardiolipin antibodies. Clinical risks increase with higher titers.

False-positive tests for syphilis have been noted in 25% of SLE patients and in fact may precede SLE by years. The "false" nature is confirmed when aTreponema pallidumimmobilization test or fluorescent treponemal antibody absorption test is negative. There is no rationale for performing tests for syphilis in patients with SLE unless syphilis is suspected.

The erythrocyte sedimentation rate is elevated in most patients with SLE and is thought by some observers to correlate with clinical activity (seeChapter 282).

RENAL MANIFESTATIONS.

Clinical lupus nephritis is observed in about 50% of SLE patients and is characterized by either urinary or functional (e.g., clearance) abnormalities. Also, many more patients have electron microscopic and/or immunofluorescence evidence of immune complex deposits in the glomeruli, even in the absence of light microscopic abnormalities. The presence of clinical lupus nephritis is of concern because of its potential for morbidity and mortality.

Minimal or mesangial nephritis (type II) develops in about 24% of patients. Patients may have some urinary abnormalities, the glomerular filtration rate is usually normal, complement levels may be somewhat depressed, and anti-DNA antibodies may be somewhat elevated. The prognosis is very good. Focal proliferative nephritis (type III) develops in 15% of patients; the clinical picture is similar to that of mesangial (type IIB) disease but is somewhat more severe. The prognosis is good.