SLE systeimic lupus erythematosisi  Prof Dr Muzamil Shahzad

 SLE is an inflammatory autoimmune disorder characterized by autoantibodies to nuclear antigens. It can affect multiple organ systems.).

 Many of its clinical manifestations are secondary to the trapping of antigen-antibody complexes in capillaries of visceral structures or to autoantibody-mediated destruction of host cells (eg, thrombocytopenia

 The clinical course is marked by spontaneous remission and relapses. The severity may vary from a mild episodic disorder to a rapidly fulminant, life- threatening illness.

 The incidence of SLE is influenced by many factors, including gender, race, and genetic inheritance. About 85% of patients are women.

 Sex hormones appear to play some role; most cases develop after menarche and before menopause. Among older individuals, the gender distribution is more equal.  Race is also a factor, as SLE occurs in 1:1000 white women but in 1:250 black women

Criteria for the classification  1. Malar rash  2. Discoid rash  3. Photosensitivity  4. Oral ulcers

 5. Arthritis  6. Serositis

 7. Kidney disease  8. Neurologic disease  Psychosis  FITS

 9. Hematologic disorders  Hemolytic anemia  Thrombocytopenia  Leucopenia  Lymphopenia

10. Immunologic abnormalities  a. Positive LE cell preparation  b. Antibody to native DNA  c. Antibody to Sm  d. False-positive serologic test for syphilis

 11. Positive ANA

 The diagnosis of SLE can be made with reasonable probability if 4 of the 11 criteria

Symptoms and Signs  The systemic features include fever, anorexia, malaise, and weight loss. Most patients have skin lesions at some time; the characteristic "butterfly" (malar) rash affects less than half of patientsThe clinical course is marked by spontaneous remission and relapses. The severity may vary from a mild episodic disorder to a rapidly fulminant, life-threatening illness.

 The clinical course is marked by spontaneous remission and relapses. The severity may vary from a mild episodic disorder to a rapidly fulminant, life- threatening illness.

 Joint symptoms, with or without active synovitis, occur in over 90% of patients and are often the earliest manifestation. The arthritis is seldom deforming; erosive changes are almost never noted on radiographs. Subcutaneous nodules are rare

 Ocular manifestations include conjunctivitis, photophobia, transient or permanent monocular blindness, and blurring of vision. 

 Cotton-wool spots on the retina (cytoid bodies) represent degeneration of nerve fibers due to occlusion of retinal blood vessels

 Pleurisy, pleural effusion, bronchopneumonia, and pneumonitis are frequent. Restrictive lung disease can develop. Alveolar hemorrhage is rare but life-threatening

 The pericardium is affected in the majority of patients. Cardiac failure may result from myocarditis and hypertension. Cardiac arrhythmias are common.

 Atypical verrucous endocarditis of Libman-Sacks is usually clinically silent but occasionally can produce acute or chronic valvular incompetence—most commonly mitral regurgitation—and can serve as a source of emboli

 Mesenteric vasculitis occasionally occurs in SLE and may closely resemble polyarteritis nodosa, including the presence of aneurysms in medium-sized blood vessels. Abdominal pain (particularly postprandial), ileus, peritonitis, and perforation may result

 Neurologic complications of SLE include  psychosis,  cognitive impairment,  seizures,

 peripheral and cranial neuropathies, transverse myelitis, and  strokes.  Severe depression and psychosis are sometimes exacerbated by the administration of large doses of corticosteroids

 Several forms of glomerulonephritis may occur, including  mesangial,  focal proliferative,  diffuse proliferative, and membranous

Laboratory Findings  SLE is characterized by the production of many different autoantibodies.  Antinuclear antibody tests are sensitive but not specific for SLE— ie, they are positive in virtually all patients with lupus but are positive also in many patients with nonlupus conditions such as rheumatoid arthritis, autoimmune thyroid disease, scleroderma, and Sjögren syndrome.

 Antibodies to double-stranded DNA and to Sm are specific for SLE but not sensitive, since they are present in only 60% and 30% of patients, respectively.  Depressed serum complement—a finding suggestive of disease activity—often returns toward normal in remission.  Anti-double-stranded DNA antibody levels also correlate with disease activity in some patients; anti-Sm levels do not

Treatment  Minor joint symptoms can usually be alleviated by rest and NSAIDs

 Antimalarials (hydroxychloroquine) may be helpful in treating lupus rashes or joint symptoms and appear to reduce the incidence of severe disease flares.  The dose of hydroxychloroquine is 200 or 400 mg/d orally and should not exceed 6.5 mg/kg/d; annual monitoring for retinal changes is recommended

 Corticosteroids are required for the control of certain complications. (Systemic corticosteroids are not usually given for minor arthritis, skin rash, leukopenia, or the anemia associated with chronic disease.)

 Glomerulonephritis,  hemolytic anemia,  pericarditis or myocarditis,  alveolar hemorrhage,  central nervous system involvement  thrombotic thrombocytopenic purpura all require corticosteroid treatment and often other interventions as well.

 Forty to 60 mg of oral prednisone is often needed initially; however, the lowest dose of corticosteroid that controls the condition should be used

 Central nervous system lupus may require higher doses of corticosteroids than are usually given; however, corticosteroid psychosis may mimic lupus cerebritis, in which case reduced doses are appropriate.

 Forty to 60 mg of oral prednisone is often needed initially; however, the lowest dose of corticosteroid that controls the condition should be used

 Cyclophosphamide, which improves renal survival but not patient survival, has been for many years the standard treatment for both phases of lupus nephritis.  Mycophenolate mofetil appears to be an effective alternative treatment for many patients with lupus nephritis. Very close follow-up is needed to watch for potential side effects when immunosuppressants are given; theagents should be administered by clinicians experienced in their use.

Course & Prognosis  The prognosis for patients with systemic lupus appears to be considerably better than older reports implied. From both community settings and university centers, 10-year survival rates exceeding 85% are routine.

 In most patients, the illness pursues a relapsing and remitting course. Prednisone, often needed in doses of 40 mg/d orally or more during severe flares, can usually be tapered to low doses (5– 10 mg/d) when the disease is inactive.  However, there are some in whom the disease pursues a virulent course, leading to serious impairment of vital structures such as lung, heart, brain, or kidneys, and the disease may lead to death

 Patients with SLE should receive influenza vaccination every year and pneumococcal vaccination every 5 years. Since some reports indicate that SLE patients have a higher risk of developing malignancy, preventive cancer screening recommendations should be followed assiduously.

. With more patients living longer, it has become evident that avascular necrosis of bone, affecting most commonly the hips and knees, is responsible for substantial morbidity. Still, the outlook for most patients with SLE has become increasingly favorable