conjunctivitis, and urethritis in ReA, spondylitis in AS, tophi in gout, butterßy rash in SLE, and so on.

6.1.2Systemic Lupus Erythematosus

Systemic lupus erythematosus is an autoimmune disease in which organs and cells undergo damage mediated by tissue-binding autoantibodies and immune complexes. The clinical course of SLE may be mild or severe and recurrent or continuous with a wide range of inßammatory manifestations in almost any organ of the body.

6.1.2.1 Epidemiology

The prevalence of SLE in urban areas of the USA ranges from 15.5 to 50.0 cases per 100,000. Onset of symptoms is more frequent between ages 15 and 45 years, women are nine times more likely to be affected than men, and it is more common among AfricanÐAmericans than among Caucasians [179, 180]. The prevalence of SLE among black women in the USA between ages 15 and 64 is one case per 245, whereas that for all women of the same ages is 1/700 [179]. SLE occurs in relatives of patients with the disease with a frequency between 0.4 and 5%, representing a several 100-fold increase over that of the general population [181]. Analysis of SLE families suggests that both genetic predisposition and environmental stimuli are important in the development of the disease; multiple interacting genes, within and outside of the major histocompatibility complex (MHC) [182], and environmental stimuli, such as viral infection, ultraviolet irradiation, or contact with certain drugs (hydralazine, procainamide, penicillin, sulfonamides, gold, phenytoin, isoniazide, and methyldopa) [183], may induce immunological alterations resulting in the formation of autoantibodies, including ANA.

6.1.2.2 Systemic Manifestations

Because constitutional symptoms are usually present at the time of diagnosis, any patient with fatigue, loss of weight, fever, malaise, and anorexia who is found to have ANAs in serum should be carefully studied for possible SLE.

Table 6.5 Common systemic manifestations of systemic lupus erythematosus

Articular: arthralgias and arthritis

Cutaneous: rash, alopecia, ulcers, and photosensitivity Renal: glomerulonephritis

Cardiovascular: pericarditis, RaynaudÕs phenomenon, and thrombophlebitis

Gastrointestinal: nausea, vomiting, and abdominal pain Neurologic: behavioral disturbance, seizures, and mononeuritis

Pulmonary: pleural effusions, pleurisy, and pneumonitis

Miscellaneous: splenomegaly, lymphadenopathy, and parotid swelling

Ocular: keratitis, episcleritis, scleritis, and retinopathy

Although almost any organ in the body can be affected, the most common systemic manifestations are shown in Table 6.5 and are described here.

Musculoskeletal

Joint disease is the most common involvement of SLE (95%) and occurs as the initial manifestation of the disease in many cases (55%) [184, 185]. In some SLE patients, joint pain or swelling may precede the onset of multisystem disease by 6 months to 5 years. The joint involvement is symmetrical and most commonly affects the proximal interphalangeal, knee, wrist, and metacarpophalangeal joints. Some SLE patients (about 15%) develop deforming arthritis changes, such as swan-neck deformities and ulnar deviation of the Þngers, similar to those seen in RA patients. Erosive arthritis is rare in SLE [186]. Myalgia, proximal muscle weakness, or muscle tenderness is common in patients with active disease [187]. Rheumatoid nodules occur in 5Ð7% of patients with SLE [17, 18].

Tegument

Cutaneous abnormalities occur in 80% of SLE patients and may be the Þrst manifestation of the disease in many cases (about 20%) [188]. The typical lesion, the butterßy facial rash, is slightly edematous and is located on both cheeks and across the bridge of the nose (Fig. 6.7). Although the rash is present in about half the patients at the moment of the diagnosis, it may be the Þrst manifestation of

the disease, preceding the multisystem involvement by weeks or months. The rash may be continuous or intermittent and is exacerbated by ultraviolet exposure, alcohol ingestion, or nervousness. The second most common rash is a maculopapular eruption, frequently pruritic and located at any place on the body.

Alopecia occurs in 25Ð40% of the patients with SLE. Because in many patients recurrent diffuse alopecia may be the Þrst manifestation of an impending SLE ßare-up, its presence should be viewed as evidence of disease activity.

Periungual erythema, atrophic blanche lesions, hives or angioneurotic edema, urticaria, bullous lesions, and nail deformities have also been described.

Vessels

Aside from RA, the connective tissue disease in which vasculitis occurs most frequently is SLE. Skin vasculitic lesions, noted in about 20% of patients with SLE, are most commonly located on the extensor surface of the forearm and on the Þngertips, but they also may be on the palms, soles of the feet, and lower legs near the malleoli. These lesions may ulcerate, particularly during the periods of disease exacerbation. Livedo reticularis, purpura, and splinter hemorrhages may also be noted in severe active disease. Mucosal vasculitic lesions, such as mucous membrane ulcers (nasal septum, palate, larynx, pharynx, and vagina), may be the Þrst manifestation of an impending SLE ßare-up.

RaynaudÕs phenomenon may occur in about 20% of SLE patients (Fig. 6.8). It is usually present with other manifestations at the time of diagnosis but occasionally may precede the onset of multisystem disease [189]. RaynaudÕs phenomenon may gradually disappear as the disease goes into remission, although in active SLE may result in digital gangrene with amputation of the Þngertips. Deep vein thrombosis also may occur and may be migratory and recurrent [189].

Peripheral neuropathy and cranial nerve involvement are characterized by arterial damage in nerve biopsy specimens. Psychosis, seizures, hemiparesis, and chorea may be the result of vasculitic cerebral involvement [189, 190].

Organ infarction, such as cerebral thrombosis and hemorrhages, myocardial infarction, diffuse proliferative lupus nephritis, or bowel perforation, may be caused by an arteritis of both smalland medium-sized arteries. Widespread necrotizing arteritis mimicking PAN has been described in a few patients with SLE.

Kidney

Although only 40Ð50% of patients have clinical evidence of renal disease (proteinuria or hematuria, nephrotic syndrome, or renal failure), nearly all show changes on renal biopsy. The spectrum of kidney involvement includes (1) focal proliferative lupus nephritis (mild), (2) diffuse proliferative lupus nephritis (severe), (3) membranous lupus nephritis (moderate), and (4) mesangial lupus nephritis (minimal) [191]. Hypertension is commonly associated. The extent and severity of the renal lesions correlate with the severity of the disease, and end-stage renal disease is the most common cause of death in patients with SLE.

Hearth

The most frequent cardiac manifestation in SLE is pericarditis, which occurs in about 25% of patients, often during acute exacerbations. Although a pericardial rub is easily detected, echocardiography is most helpful in detecting pericardial thickening [192]. Myocardial involvement may present as tachycardia, cardiac enlargement, congestive heart disease, arrhythmias, conduction defects, or even cardiac failure. Deaths caused by myocardial infarction from coronary arteritis have been reported early in the course of the disease in young patients [189, 193, 194]. Atypical verrucous endocarditis, termed LibmanÐSacks endocarditis, is usually of little clinical signiÞcance and is not easily diagnosed in life. The pathological Þndings at necropsy reveal ovoid vegetations, from 1 to 4 mm of diameter, made up of degenerating valve tissue with Þbrin and platelet thrombi. Although the original descriptions by Libman and Sacks [195] were observed on the tricuspid valve, more recent series show a higher incidence of lesions on the mitral valve [196]. Subacute bacterial endocarditis may occur when microorganisms become