系统性红斑狼疮——英语.docx

1、Chapter 289SYSTEMIC LUPUS ERYTHEMATOSUSPeter H. SchurSystemic lupus erythematosus (SLE) is a disease of unknown cause that may produce variable combinations of fever, rash, hair loss, arthritis, pleuritis, pericarditis, nephritis, anemia, leukopenia, thrombocytopenia, and central nervous system (CNS

2、) disease. The clinical course is characterized by periods of remissions and acute or chronic relapses. Characteristic immune abnormalities, especially antibodies to a number of nuclear and other cellular antigens, develop in patients with SLE. The diagnosis is facilitated by determining whether the

3、 patient has 4 of the 11 clinical and/or laboratory criteria developed for the classification of SLE(Table 289-1).EPIDEMIOLOGY.SLE can occur at any age but has its onset primarily between ages 16 and 55. It occurs more frequently in women. In children, the female-male ratio is 1.4 to 5.8:1; in adult

4、s, it ranges from 8:1 to 13:1; and in older individuals, the ratio is 2:1. The prevalence of SLE is estimated to be between 4 and 250 cases per 100,000 population. In theUnited States, the highest incidence is among Asians inHawaii, blacks, and certain Native Americans (Sioux, Crow, Arapahoe). The r

5、isk of SLE developing in a black American female has been estimated to be 1:250. The prevalence is about the same worldwide; the disease appears to be common inChina, in Southeast Asia, and among blacks in the Caribbean, but is seen infrequently in blacks inAfrica. Limited observations suggest that

6、the incidence of discoid lupus erythematosus is the same as that for SLE.ETIOLOGY.The cause of SLE remains unknown, although many observations suggest a role for genetic, hormonal, immune, and environmental factors. The evidence for a genetic role is summarized inTable 289-2. Some of these genetic m

7、arker associations are found more frequently in SLE patients of different races and ethnicities. It has been calculated that at least four genes are involved in predisposing individuals to SLE. Each gene presumably affects some aspect of immune regulation, protein degradation, peptide transport acro

8、ss cell membranes, immune response, complement, the reticuloendothelial system (including phagocytosis), immunoglobulins, apoptosis, and sex hormones. Thus combinations of dissimilar gene defects may result in distinct abnormal responses and produce separate pathologic processes and different clinic

9、al expression.The evidence for hormonal abnormalities is based primarily on the observation that SLE is much more common among women in their childbearing years. In addition, SLE has been observed in some males with Klinefelters syndrome, and some abnormalities of estrogen metabolism have been noted

10、 in both men and women with SLE. However, the clinical expression of SLE is the same in men and women. Furthermore, a lupus-like disease ofNew Zealandmice is more common and more severe and has an earlier onset in females-and is ameliorated by oophorectomy or treatment with male hormones. However, i

11、n other strains of mice with a lupus-like disease, this gender difference is not noted.Numerous immune abnormalities occur in patients with SLE, the etiology of which remains unclear; nor do we know which are primary and which are secondary. Some of these immune defects are episodic, and some correl

12、ate with disease activity. SLE is primarilyPATHOGENESIS.Many manifestations are mediated by antibodies. The classic example is that of diffuse proliferative glomerulonephritis. Immune complexes, which consist of nuclear antigens (especiallyDNA) and high-affinity complement-fixing IgG (especially IgG

13、1 and IgG3) and ANAs (especially antibodies to DNA), form in the circulation and are deposited in the glomerular basement membrane (GBM) or form in situ; histone may facilitate immune complex deposition. The complement system is then activated and chemotactic factors are generated. These factors ind

14、uce the attraction and infiltration of leukocytes, which then phagocytose immune complexes and cause the release of mediators (such as activators of the clotting system), which further perpetuate the glomerular inflammation. With continuing immune complex deposition, chronic inflammation may ensue,

15、ultimately leading to fibrinoid necrosis and scarring (crescents) and loss of renal function. In lupus membranous glomerulonephritis, similar mechanisms occur, although immune complex-containing, poorly complement-fixing IgG2 and IgG4 form primarily in situ on the GBM; there is no cellular infiltrat

16、e. The mechanism for the GBM protein leakage, which results in the nephrotic syndrome, is not clear. In lupus mesangial glomerulonephritis, mesangial cells (macrophage-likePATHOLOGY.Few unique pathologic features are associated withSLE. In patients with arthritis, the synovial histopathology tends t

17、o be non-specific, with superficial fibrin-like material and local or diffuse cell lining proliferation. Vascular changes include perivascular mononuclear cells, lumen obliteration, enlarged endothelial cells, and thrombi, but fibrinoid necrosis is uncommon. Biopsies of the malar erythema may reveal

18、 some minor basal layer abnormalities, as well as immune complex deposits at the dermal-epidermal junction. Discoid skin lesions are characterized by hyperkeratosis, follicular plugging, and more basal cell layer changes, including immune complexes at the dermal-epidermal junction. Pleura and perica

19、rdium are infiltrated by mononuclear cells. Lupus pneumonitis is characterized by alveolar wall injury, hemorrhage, and edema; hyaline membrane formation; and immune complex deposits. Coronary arteries often demonstrate premature-onset atherosclerosis. Libman-Sacks endocarditis is characterized by t

20、he accumulation of immune complexes, mononuclear cells, hematoxylin bodies, and fibrin and platelet thrombi. Pathologic examination of the spleen often reveals an onion skin appearance of the splenic arteries, which is thought to represent healed arteritis.RENAL DISEASE.Minimal disease (type IIA mes

21、angial disease) of glomeruli has immune complex deposits only in mesangial cells. Type IIb mesangial nephritis also has mesangial hypercellularity. Focal proliferative nephritis (type III) has segmental proliferation in glomerular tufts and in the mesangium and immune complex deposits in the mesangi

22、um and scattered granular deposits in the subendothelial, subepithelial, and intrabasement GBM. Active diffuse proliferative glomerulonephritis (type IV) affects more than 50% of glomeruli with cellular proliferation, necrosis, wire loops, subendothelial deposits, and hematoxylin bodies. When chroni

23、c, the process involves sclerosis, adhesions, crescents, and (tubular) atrophy. Extensive lumpy and bumpy deposits of immune complexes are present. In membranous nephritis (type V) diffuse, uniform thickening of the GBM is seen, with a fine granular deposition of immune complexes in the subendotheli

24、al region beneath fused foot processes. Tubular degenerative changes with interstitial mononuclear cells are not uncommon. Extensive crescent formation, representing scarring, indicates a poor prognosis.The brain is notable for the paucity of pathologic changes. Some minor blood vessel abnormalities

25、, an occasional microinfarct, and some perivascular infiltration have been noted.CLINICAL MANIFESTATIONS.SLE is highly variable in onset as well as course. The initial symptoms may be non-specific(Table 289-4)and include myalgia, nausea, vomiting, headaches, depression, easy bruising, or more specif

26、ic symptoms or any combination thereof. These symptoms may be mild or severe, fleeting or persistent.GENERAL SYMPTOMS.Fatigue occurs in virtually all patients with SLE. Fatigue may parallel the onset of SLE or its relapse but should be distinguished from the fatigue associated with other factors suc

27、h as increased workload, sleep disturbance, depression, unhealthful habits, stress, deconditioning, anemia, the use of certainmedications (including prednisone), and any intercurrent disease. Fever is seen in 80% of patients; it is usually episodic. Infections, which occur commonly in SLE patients,

28、must always be considered.MUSCULOSKELETAL MANIFESTATIONS.Arthralgia and arthritis have been noted in 95% of patients with SLE. Symptoms tend to be asymmetrical and migratory, with complaints in a particular joint often gone in 1 to 3 days. Fingers, hands, wrists, knees, and less frequently, ankles,

29、elbows, shoulders, and hips are affected. Morning stiffness is generally measured in minutes, in contrast to hours in rheumatoid arthritis. Although joint deformities are considered to be more a feature of rheumatoid arthritis, damage to periarticulaPULMONARY MANIFESTATIONS.Pulmonary involvement occ

30、urs 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) a

31、lso 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, the

32、y 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, c

33、ough (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 complicateSLEbut is more frequent with scleroderma o