Systemic Lupus Erythematosus: Organ Manifestations and Laboratory Assessment

Ninety percent of SLE cases occur in women, usually of child-bearing age. Almost all patients experience arthralgias and myalgias, and most develop intermittent arthritis. Erosions are rare; the differentiating joint feature is nonerosive arthritis.

Most patients with SLE have immunoglobulin deposits in the glomeruli, but only one-half have clinical nephritis, defined by proteinuria. Early disease is asymptomatic in most patients, although some develop nephrotic-syndrome edema. Urinalysis shows hematuria, cylindruria, and proteinuria.

Thrombosis in vessels of any size can be a major problem. Although vasculitis may underlie thrombosis, increasing evidence associates antibodies against phospholipids—lupus anticoagulant (LA) and anticardiolipin (ACL)—with clotting without inflammation.

ANAs are the best screening test. Antibodies to double-stranded DNA (dsDNA) and to CM are relatively specific for SLE. High serum ANA and anti-dsDNA levels together with low complement levels usually reflect disease activity, especially in patients with nephritis. Very low CH50 with normal C3 is seen.

Most patients complete pregnancy safely and deliver normal infants, and fertility rates are normal. However, spontaneous abortion and stillbirth are frequent, occurring in 10–30%, especially among women with lupus anticoagulant and/or anticardiolipin.

Myopathy may be inflammatory during active disease or secondary to treatment, including hypokalemia, glucocorticoid myopathy, and hydroxychloroquine myopathy. In patients receiving glucocorticoids, ischemic necrosis of bone is a common cause of pain in the hip, knee, or shoulder.

Papillary necrosis and wire-loop lesions are seen. Most patients with mesangial or mild focal proliferative nephritis maintain good renal function. By contrast, diffuse proliferative nephritis leads to renal failure if untreated. Renal involvement is the most common cause of death.

During active lupus, anemia of chronic disease occurs in most patients. Autoimmune hemolytic anemia is seen, including Coombs-positive hemolysis; cold antibodies also occur. Leukopenia is usually lymphopenia; mild thrombocytopenia is common, and pancytopenia can occur.

Hematologic abnormalities include anemia—usually normochromic normocytic but occasionally hemolytic—plus leukopenia, lymphopenia, and thrombocytopenia. The Westergren erythrocyte sedimentation rate correlates with disease activity in some patients. Perform urinalysis and measure serum creatinine periodically. Active nephritis usually produces proteinuria, hematuria, and cellular or granular casts.

Neonatal lupus results from transmission of maternal anti-Ro across the placenta. Manifestations consist of a transient skin rash and, rarely, permanent heart block. Transient thrombocytopenia also occurs because of maternal antiplatelet antibodies.

The malar “butterfly” rash is a photosensitive, fixed erythematous eruption. It may be flat or raised and extends over the cheeks and bridge of the nose, often involving the chin and ears. Scarring is absent, although telangiectasia may develop.

Mild cognitive dysfunction is the most frequent nervous-system manifestation of SLE. Headaches are common and may be either migraine-like or nonspecific, whereas seizures of any type may occur. Depression and anxiety are also frequent.

Clinical manifestations associated with lupus anticoagulant and anticardiolipin include thrombocytopenia, recurrent venous or arterial clotting, recurrent fetal loss, and valvular heart disease. These manifestations usually respond to glucocorticoids; clotting syndromes do not.

Drugs that can cause an SLE-like syndrome include procainamide, hydralazine, isoniazid, chlorpromazine, D-penicillamine, practolol, methyldopa, quinidine, and interferon A; hydantoin, ethosuximide, and oral contraceptives are possible causes. The syndrome is rare with all except procainamide—the most frequent offender—and hydralazine. Genetic predisposition is partly determined by drug acetylation rates.

A diffuse maculopapular rash that predominates in sun-exposed areas is also common and usually indicates a disease flare. Scalp hair loss is usually patchy but can be extensive.

Less frequent lesions include:

• Urticaria and bullae
• Erythema multiforme
• Lichen planus-like lesions
• Panniculitis called lupus profundus

Less frequent manifestations include psychosis, acute confusional states, demyelinating or movement disorders, cerebrovascular disease, aseptic meningitis, myelopathy, autonomic dysfunction, mood disorders, optic neuritis, subarachnoid hemorrhage, pseudotumor cerebri, and hypothalamic dysfunction with inappropriate vasopressin secretion. Cranial or peripheral mononeuropathy or polyneuropathy and acute demyelinating polyneuropathy (Guillain-Barre) may also occur.

Pericarditis is the most frequent cardiac manifestation. Effusions can occur and occasionally cause tamponade; constrictive pericarditis is rare. Myocarditis can cause arrhythmias, sudden death, and/or heart failure. Aortic or mitral insufficiency can occur with or without Libman-Sacks endocarditis. Myocardial infarcts usually reflect degenerative disease, although they can result from vasculitis.

Systemic complaints and arthralgias are most common in drug-induced lupus; polyarthritis and pleuropericarditis also occur. Renal and central nervous system involvement are rare. All patients have ANA, most have antibodies to histones, and antibodies to histones are the “best marker.”

Patients with SLE can develop a broad spectrum of vasculitic skin lesions. These include:

• Purpura and subcutaneous nodules
• Nailfold infarcts and ulcers
• Vasculitic urticaria and panniculitis
• Gangrene of the digits

Mucosal disease is also frequent: ulcers of the mouth and nose are shallow and slightly painful.

Pleurisy and pleural effusions are common. Other findings include lung cavitation, pulmonary fibrosis, shrinking lung syndrome, and polyserositis. Lupus pneumonitis causes fever, dyspnea, and cough; radiographs show fleeting infiltrates and/or plate-like atelectasis, and the syndrome responds to glucocorticoids. However, infection is the most common cause of pulmonary infiltrates in SLE.