1. RENAL & CARDIAC MANIFESTATIONS OF SLE

2. Systemic lupus erythematosus
Patients with SLE are subject to a variety of symptoms, complaints, and inflammatory involvement that can affect virtually every organ
The most common pattern is a mixture of constitutional complaints with skin, musculoskeletal, mild hematologic, and serologic involvement

3. CLINICAL CRITERIA FOR DIAGNOSIS
Most physicians rely on the ARA revised Criteria for the Classification of SLE
The diagnosis of SLE is made if four or more of the manifestations are present, either serially or simultaneously
When tested against other rheumatic diseases, these criteria have a sensitivity and specificity of approximately 96 percent

4. ARA Criteria for diagnosis of Systemic Lupus Erythematosus
criterion definition
malar rash fixed erythema, flap or raised, over the mainandevidence

5. AUTOANTIBODIES
The ANA test is the best screening test for SLE and should be performed whenever SLE is suspected
The ANA is positive in significant titer (usually 1:160 or higher) in virtually all patients with SLE

6. AUTOANTIBODIES dsDNA and Sm antibodies
There are two autoantibodies that are highly specific for SLE
anti-double-stranded DNA (dsDNA) antibodies
anti-Sm antibodies
Sensitivity – 66 to 95 percent
Specificity – 75 to 100 percent
Predictive value – 89 to 100 percent

7. Renal manifestations of SLE
Renal involvement is common in SLE
An abnormal urinalysis is present in approximately 50% of patients at the time of diagnosis and eventually develops in more than 75 percent of cases
The most frequently observed abnormality is proteinuria (80 percent); while approximately 40 percent have hematuria and/or pyuria sometime during the course of their illness

8. Renal manifestations of SLE
The total incidence of renal involvement among patients with SLE probably exceeds 90 percent since renal biopsy in patients without any clinical evidence of renal disease often reveals a focal or diffuse proliferative glomerulonephritis
There are a number of different types of renal disease in SLE, with immune complex-mediated glomerular diseases being most common

9. IMMUNE COMPLEX GLOMERULAR DISEASE
Most patients with lupus nephritis have an immune complex-mediated glomerular disease
The standard classification divides these disorders into five different patterns in which (type I) represents no disease
Mesangial (type II)
Focal proliferative (type III)
Diffuse proliferative (type IV)
Membranous (type V)

10. Mesangial lupus nephritis (type II)
Occurs in 10 to 20% of cases and represents the earliest and mildest form of glomerular involvement
Presents clinically as microscopic hematuria and/or proteinuria; hypertension is uncommon, and the nephrotic syndrome and renal insufficiency are virtually never seen
The renal prognosis is excellent and no specific therapy is indicated unless the patient progresses to more advanced disease

11. Mesangial proliferative glomerulonephritis
Mesangial proliferative glomerulonephritis. Light micrograph of a mesangial glomerulonephritis showing segmental areas of increased mesangial matrix and cellularity (arrows). This finding alone can be seen in many diseases, including lupus nephritis and IgA nephropathy.

12. Focal proliferative lupus nephritis (type III)
Occurs in 10 to 20% of cases, but represents more advanced involvement than mesangial disease
Hematuria and proteinuria are seen in almost all patients, some of whom also have the nephrotic syndrome, hypertension, and an elevated plasma creatinine concentration
By definition, less than 50 percent of glomeruli are affected on light microscopy
Electron microscopy shows immune deposits in the subendothelial space of the glomerular capillary wall as well as the mesangium

13. Focal proliferative lupus nephritis (type III)
The renal prognosis in focal proliferative lupus nephritis is variable
Progressive renal dysfunction appears to be uncommon when less than 25 percent of the glomeruli are affected on light microscopy
On the other hand, more widespread or severe involvement (40 to 50 percent of glomeruli affected, nephrotic range proteinuria, and/or hypertension) has a long-term prognosis that is similar to that of diffuse disease

14. Memberanoproliferative lupus nephritis
Memberanoproliferative lupus nephritis. Light micrograph showing a memberanoproliferative pattern in lupus nephritis, characterized by areas of cellular proliferation (long arrows) and by thickening of the glomerular capillary wall (due to immune deposits) that may be prominent enough to form a “wire-loop” (short arrows). Although proliferative changes can be focal (affecting less than 50% of glomeruli), disease ofthis severity is usually diffuse.

15. Diffuse proliferative lupus nephritis (type IV)
The most common and most severe form of lupus nephritis affecting 40 to 60% of cases
Hematuria and proteinuria are seen in almost all cases, and the nephrotic syndrome, hypertension, and renal insufficiency are all frequently seen
Affected patients typically have significant hypocomplementemia and elevated anti-DNA levels, especially during active disease
Immunosuppressive therapy is generally required to prevent progression of active diffuse proliferative lupus nephritis to ESRD

16. Diffuse proliferative lupus nephritis
Diffuse proliferative lupus nephritis. Kidney biopsy from a patient with diffuse proliferative lupus nephritis showing, on immunofluorescence microscopy, massive lumpy bumpy deposits of IgG.

17. Membranous lupus (type V)
Affects 10 to 20 percent of patients
Patients typically present with nephrotic syndrome
Microscopic hematuria and hypertension also may be seen at presentation, and the plasma creatinine concentration is usually normal or slightly elevated
Membranous lupus is the one form of lupus nephritis that may present with no other clinical or serologic manifestations of SLE
Most patients maintain a normal or near normal plasma creatinine concentration for five years or more and may not require immunosuppressive therapy

18. Membranous lupus nephritis
Membranous lupus nephritis. Light micrograph of membranous lupus nephritis. The changes are similar to those in any form of membranous nephropathy with diffuse thickening of the glomerular capillary wall being the major abnormality (short arrows). Focal areas of mesangial expansion and hypercellularity (long arrows) are the only findings suggestive of an underlying disease such as lupus, although they can also be seen in idiopathic membranous nephropathy.

19. Membranous lupus nephritis
Membranous lupus nephritis. Electron micrograph of membranous lupus nephritis. The subepithelial immune deposits (D) are characteristic of any form of membranous nephropathy, but the intraendothelial tubuloreticular structures (arrow) strongly suggest underlying lupus. GBM = glomerular basement membrane; EP = epithelial cell.

20. Other Renal manifestations of SLE
In addition to these glomerulopathies, there are three other less common forms of lupus renal disease
interstitial nephritis;
vascular disease; and
renal disease infrequently associated with drug-induced lupus

21. Tubulointerstitial nephritis
Tubulointerstitial disease (interstitial infiltrate, tubular injury) is a common finding in lupus nephritis, almost always being seen with concurrent glomerular disease
The severity of the tubulointerstitial involvement is an important prognostic sign, correlating positively with the presence of hypertension, an elevated plasma creatinine concentration, and a progressive course

22. Vascular disease
Involvement of the renal vasculature is not uncommon in lupus nephritis and its presence can adversely affect the prognosis of the renal disease
The most common problems are immune complex deposition, immunoglobulin microvascular casts, a thrombotic microangiopathy leading to a syndrome similar to TTP, and vasculitis
Vascular immune deposits typically produce no inflammation, but fibrinoid necrosis with vascular narrowing can be seen in severe cases

23. Vascular disease
Other patients present with glomerular and vascular thrombi, often in association with antiphospholipid antibodies
Renal involvement is characterized by fibrin thrombi in the small arteries and glomerular capillaries and, in some cases, in the larger renal artery branches
These changes may occur as a primary disease or may be superimposed upon one of the immune complex forms of lupus nephritis
Rarely, patients with lupus nephritis develop renal vein thrombosis

24. Drug-induced lupus
A variety of drugs can induce a lupus-like syndrome, particularly those that are acetylated in the liver, such as hydralazine, procainamide, and less often isoniazid
Renal involvement is uncommon but a proliferative glomerulonephritis or the nephrotic syndrome can occur

25. Cardiac manifestations of SLE
Cardiac disease is common among patients with SLE as pericardial, myocardial, valvular, and coronary artery involvement can occur
The incidence of these problems can be summarized as follows
Cardiac abnormalities – up to 55 percent
Valvular disease – up to 50 percent
Pericardial disease, usually a clinically silent effusion – up to 48 percent
Myocardial dysfunction – up to 78 percent

26. VALVULAR DISEASE
Systolic murmurs have been noted in 16 to 44 percent of patients
Structural valvular disease is most common but anemia, fever, tachycardia, and cardiomegaly can induce functional murmurs
Diastolic murmurs have been noted in one to three percent of patients
They often reflect aortic insufficiency, which occasionally requires valve replacement.

27. VALVULAR DISEASE
Mitral valve involvement is most common; a mild to moderate regurgitant murmur may be heard but most patients remain asymptomatic
Mitral valve prolapse appears to occur with increased frequency in lupus, occurring in 25 percent of cases

28. Verrucous endocarditis
Libman-Sacks endocarditis is a not uncommon complication of SLE
In one report of 74 patients, seven had verrucous lesions detected by TTE
However, a higher frequency (43 percent) has been noted when more sensitive TEE is performed
In addition, Libman-Sacks endocarditis is often associated with antiphospholipid antibodies
Verrucous endocarditis is typically asymptomatic
However, the verrucae can fragment and produce systemic emboli

29. PERICARDIAL DISEASE
Pericardial involvement is the second most common echocardiographic lesion in SLE, and is the most frequent cause of symptomatic cardiac disease
Pericardial effusion occurs at some point in over one-half of patients, and a benign pericarditis may precede the clinical signs of lupus
Pericardial disease is usually asymptomatic, and is generally diagnosed by echocardiography performed for some other reason

30. PERICARDIAL DISEASE
Symptomatic pericarditis typically presents with positional substernal chest pain with an audible rub on auscultation
The pericardial fluid is a fibrinous exudate or transudate that may contain antinuclear antibodies, LE cells, low complement levels, and immune complexes
The pericardium may reveal foci of inflammatory lesions with immune complexes

31. PERICARDIAL DISEASE
The course is benign in the large majority of patients with pericardial disease
Symptomatic pericarditis often responds to an NSAID, especially indomethacin
Patients who do not tolerate or respond to an NSAID can be treated with prednisone
The most serious consequence is the development of purulent pericarditis in the immunosuppressed, debilitated patient
Large effusions, suggestive of tamponade, and constrictive pericarditis are rare in SLE

32. MYOCARDITIS
Myocarditis is an uncommon, often asymptomatic manifestation of SLE with a prevalence of 8 to 25%
It should be suspected if there is resting tachycardia disproportionate to body temp., EKG abnormalities and unexplained cardiomegaly
Echocardiography may reveal abnormalities in both systolic and diastolic function of the left ventricle
Acute myocarditis may accompany other manifestations of acute SLE, particularly pericarditis
Myocarditis should be treated with prednisone plus usual therapy for congestive heart failure if present

33. CONDUCTION ABNORMALITIES
Conduction defects, which may represent a sequel of active or past pericarditis and/or myocarditis have been noted in 34 to 70 percent of patients with SLE
Congenital heart block may be part of the neonatal lupus syndrome
Many mothers of these infants have either SLE or Sjögren's syndrome, antibodies to Ro (SS-A) and/or La (SS-B), and are HLA-DR3 positive
The anti-Ro and anti-La antibodies may induce autoimmune injury that prevents normal development of the conduction fibers
It is recommended that anti-Ro antibody titers be measured early in pregnancy in women with SLE

34. CORONARY ARTERY DISEASE
Coronary artery disease has been recognized in 2 to 16% of patients with SLE and can lead to acute myocardial infarction in young women
Coronary disease, leading to angina, myocardial infarction, congestive heart failure, and death, is becoming an increasing problem, particularly in the young patient with long-standing SLE maintained on corticosteroids
In one report, coronary disease (defined as angina, myocardial infarction, or sudden death) occurred in 8.3 percent of 229 patients and was responsible for 3 of 10 deaths

35. CORONARY ARTERY DISEASE
Patients with SLE should be made aware of the importance of risk factor reduction
Patients with lupus should be advised to stop smoking, exercise, consider the use of hormone replacement therapy, and follow measures designed to improve lipid profiles
Hydroxychloroquine should be used in preference to prednisone whenever possible and aspirin should be prescribed for its antiplatelet properties
Symptomatic coronary artery disease should be treated as in patients without lupus

36. VENOUS THROMBOSIS
Thrombophlebitis has been reported in approximately 10 percent of patients with SLE
It generally involves the lower extremity, but can also affect the renal veins and inferior vena cava
Risk factors for venous thrombosis include antiphospholipid antibodies and the use of oral contraceptives, particularly in association with smoking cigarettes