Systemic Lupus Erythematosus Systemic lupus erythematosus (SLE) derives its name from the typical facial rash,

which resembles the malar erythema of a wolf. It is a multi system involving autoimmune connective tissue disease of unknown etiology. It is characteri ed by the marked diversity and heterogeneity in clinical course as well as presentation. !he clinical pattern of lupus has been changed dramatically in recent decades from originally an acute fatal disease to the chronic inflammatory autoimmune disease, occasionally fatal. It is somewhat like an inflammatory syndrome for there is no single abnormality that can definitely establish the diagnosis. "s a result criteria have been developed and modified in an attempt to make a precise diagnosis with high sensitivity and specificity. Epidemiololgy "lthough SLE can occur at any age, more than #$ % of patients e&perience the onset of disease between ages from '( to )$ years old and female patients are predominant which accounts *$ % of the patient population. So it is also a disease that mainly involves the women of childbearing age. "nyhow the illness in male is no milder despite the low incidence. SLE is more common in "frican+"merican females. ,c-arty ./ etc. reported the annual incidence of SLE is two and half times more in "frican+"merican females than that in white females. "lso in 0riental population in 1orth "merica, the disease appears to be aggressive and is associated with a higher mortality. "ccording to a survey conducted in two decades ago in Shanghai, the prevalence of the disease is around 2$ per '$$,$$$ people and ''( per '$$,$$$ in female population. It is estimated that there are one million patients in -hina. 3oth genetic factors and se& hormone are contributed to the developing of the disease. If a family member has SLE, the likelihood of SLE increases with appro&imately ($ % for identical twins and 4% for other first+degree relatives. Etiopathogenesis In SLE, there is marked disturbance in immune regulation. !hese abnormalities may have arisen from genetic, environmental and hormonal factors. !he e&act mechanism of interplay of these combined effects is still unknown. 5enetic factors are important as SLE is known to occur in families and has a different distribution among different racial or ethnic groups. !he importance of specific genes in SLE is emphasi ed by the high fre6uency of certain 7L" haplotypes, especially .89 and .8(, and null complement alleles. Sunlight, stress and microbes are the usual environmental triggers that may induce the onset, flare or e&acerbate of the disease: 7ormone factors are suspected in the pathogenesis of SLE. ,ost SLE patients are women in the childbearing age and many studies indicated that the serum level of female hormone or its derivatives is correlated with the disease activity. !here is poly+clonal 3 cell activation giving rise to the production of a plethora of autoantibodies produced in SLE patients with
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antinuclear antibodies being the most notable. 3esides this there are antibodies to other cell structures like erythrocytes, platelets and phospholipids. !here may have immune comple& deposit in ;oints, small vessels or glomeruli. !he complement system is activated and together they can cause intense inflammation and tissue in;ury. Clinical features !he general symptoms for SLE may be non+specific like fever, anore&ia, malaise, and weight loss. Skin involvement ,ost patients have skin lesions at some time: !he classic form is so called <butterfly= rash which is a characteristic erythematosus malar rash together with photosensitivity. It happens on ($+)$ % of patients. 0ther cutaneous manifestations are discoid lupus, typical fingertip lesions, peri+ungual erythema, and nail fold infarcts. "lopecia is common. ,ucous ulcer tends to occur during periods of e&acerbation. 8aynaud>s phenomenon, presenting in about 9$% of patients, often antedates other features of the disease. 7istological e&amination may show non+specific inflammation and classic immune deposits are shown at the site of dermal+epidermal ;unction by immunoflourescence. Subacute cutaneous lupus (S-LE) is a non+scaring, annular or papulos6uamous eruption in sun+e&posed areas. ?atients with S-LE have significant levels of antinuclear antibodies such as the anti+8o antibodies. .iscoid lesions are fre6uently present in the absence of other manifestations of SLE. 0ther symptoms include vasculitis lesion such as telangiectasis, nail fold infarcts, livedo reticularis or chronic skin ulcers, alopecia, angioneurotic edema, and purpura. Musculoskeletal involvement /oint symptoms, with or without active synovitis, occur in over *$% of patients and are often the earliest manifestation. @sually it presents as non+erosive arthritis happened in interphalangeal, metarcarpophalangeal ;oints, wrists and knees. !he arthritis is seldom deforming: erosive changes are almost never noted on radiographs. !enosynovitis may happen in some patients. ,yositis in SLE can account for muscle weakness and pain. 3ut corticosteroids and anti+malarial drugs (chloro6uine and hydrochloro6uine) do give rise to drug+ related myopathy and must be taken into consideration in evaluating the musculoskeletal complaints of patients. Renal involvement 8enal involvement is present in appro&imately 4$+2$% patients. It may be asymptomatic but urine sample analysis demonstrates proteinuria, hematuria and casts. Several forms of glomerulonephritis may occur, including mesangial, focal proliferative, diffuse proliferative, and membranous. Some patients may also have interstitial nephritis. Aith appropriate therapy, the survival rate even for patients with serious renal disease (proliferative glomerulonephritis) is favorable, albeit a
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small portion of patients with severe lupus nephritis still eventually re6uires renal replacement therapy. 8enal biopsy is helpful in delineating the pathological change in the way of microscopic e&amination as well as by immunofluorescence. Several histological classes have been described according to the classification of A70 listed below and it is believed that diffuse proliferative lesions and to a lesser e&tent, focal glomerular nephritis has a poorer prognosis than mesangial or membranous lupus nephritis. !ransformation of histological type does occur. "ctive diffuse type may change to the milder type via proper treatment and vice versa. Aorld 7ealth 0rgani ation classification of lupus nephritis I 1ormal glomeruli II ?ure mesangial nephritis III Bocal segmental glomerulonephritis IC .iffuse proliferative glomerulonephritis C ,embranous glomerulonephritis CI "dvanced sclerosing glomerulonephritis Cardiovascular and pulmonary involvement !he pericardium is affected in the ma;ority of patients. 0ther manifestations are myocarditis, endocarditis or coronary artery disease. ,yocarditis is often suspected when there are arrhythmias or abnormal conduction, une&plained cardiomegaly or tachycardia. -ardiac failure may result from myocarditis and hypertension. "typical verrucous endocarditis of Libman+Sacks is usually clinically silent but occasionally can produce acute or chronic valvular incompetenceDmost commonly mitral regurgitationDand can serve as a source of emboli. 3esides, coronary vasculitis duo to active disease may occur and atherosclerotic coronary artery disease occurs late in the disease process. ?leurisy, pleural effusion, bronchopneumonia, and pneumonitis are fre6uent. ?leural effusion is usually unilateral and generally e&udative in nature. "cute pneumonitis may lead to alveolar hemorrhage, though rare, but potentially life+threatening. ?atients may present with dyspnea and haemoptysis. .iffuse interstitial lung disease is characteri ed by chronic dyspnea, diffuse interstitial lung infiltrates on E+ray films, restrictive lung disease on full lung function test and fibrosis on histological e&amination. !rans+bronchial or open lung biopsy may be necessary to ascertain the diagnosis. ?ulmonary hypertension is associated with poor prognosis especially when the measured pulmonary arterial systolic pressure e&ceeds #$ mm7g. It has been ranked as the third killer for SLE patients following the infection and renal failure. Nervous system involvement 1eurologic complications of SLE are common including psychosis, organic brain syndrome, sei ures, peripheral and cranial neuropathies, transverse myelitis,
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and strokes. !he peripheral nerves are less commonly involved while the incidence of psychiatric disturbances ranges from '$+4$%. !hey may manifest as organic brain syndromes and depressive disorders. Severe psychosis are sometimes e&acerbated by the administration of large doses of corticosteroids. Gastrointestinal tract and liver involvement "ny part of the 5I tract may be involved. ?ainless oral ulcer is common while dysphagia is rare. "bdominal pain may be caused by lupus peritonitis, which usually is the result of small vessel involvement in the bowel serosa or retroperitoneum. Bever, tenderness, nausea, vomiting and diarrhea are the main symptoms presented. !hey respond well to corticosteroids. ?aracentesis is necessary to rule out bacterial peritonitis. ,esenteric vasculitis occasionally occurs in SLE. "bdominal pain (particularly postprandial), ileus, peritonitis, and perforation may result. 0ther manifestations include pancreatitis and protein+ losing enteropathy. ?ancreatitis may be due to the disease but drugs such as " athioprine ("F") must be e&cluded as the offending agent. Liver abnormalities are uncommon and may take the forms of the increase of en yme level or occasionally ;aundice. Sometimes the symptoms are caused by the drugs like 1S"I.s, immuosuppressives etc. Hematological involvement SLE can involve all the cellular elements in the bone marrow as well as the clotting system. " common manifestation is anemia but this may be due to multiple causes. "nemia of chronic disease is most common and may improve upon the control of the underlying disease process. 7emolytic anemia is another cause and is often associated with a positive -oombGs test. Leukopenia may be due to granulocytopenia or lymphopenia. !hrombocytopenia is observed in '4+94% patients. Severe thrombocytopenia is not rare and may not responsive to conventional corticosteroids therapy in a short duration. Intravenous immunoglobulin may work but the effects may not be sustained. Idiopathic thrombocytopenia purpura may precede the onset of SLE for years. !he most common clotting abnormality is caused by the presence of antiphospholipid antibodies, namely lupus anti+coagulant (L") and anti+cardiolipin antibodies. !he L" is manifested by the prolongation of the partial thromboplastin time, which is not corrected by addition of normal plasma. !he antiphopholipid antibodies have been associated with recurrent spontaneous abortions and thrombosis. Ocular involvement 0cular manifestations include con;unctivitis, photophobia, transient or permanent monocular blindness, and blurring of vision. -otton+wool spots on the retina represent degeneration of nerve fibers due to occlusion of retinal blood vessels. Laboratory findings "nemia is the commonest hematological finding in SLE. !he ma;ority present with a normochronic, normocytic anemia due to marrow suppression. " few
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develop -oombGs test positive hemolytic anemia. Leukopenia is common, but the white count rarely fails below 9$$$Hul. !hrombocytopenia is commonly seen. proteinuria (varying from mild to nephrotic range) is fre6uent during e&acerbation of the disease and to a less e&tent do shower of red blood cells and cast. !hese disorders usually abate with remission. !he sedimentation rate is high in almost all cases. ,ost patients have elevated serum levels of globulin. Serum complement levels are depressed to various degrees. ,arkedly depressed complement levels including -74$, -), and -( are seen primarily in patients with active lupus nephritis. !he low compliment levels probably reflect in vivo activation and fi&ation of complement components by circulating immune comple&es. SLE is characteri ed by the production of many different autoantibodies. "ntinuclear antibody tests are sensitive but not specific for SLEDi.e. they are positive in virtually all patients with lupus but are positive also in many patients with nonlupus conditions such as rheumatoid arthritis, various forms of hepatitis, and interstitial lung disease. !here are several patterns of immunofluorescent staining for antinuclear antibodiesI ". 3. !he <homogeneous= pattern is the morphologic e&pression of antideo&yribonucleoprotein antibodies. !he peripheral pattern is the morphologic e&pression of anti+ds.1" antibodies and antibodies to soluble nucleoprotein. It is characteristic of active SLE. !he speckled pattern reflects the presence of antibodies directed against non+.1" nuclear constituents. !he antigens to which these antibodies are directed can be e&tracted from the nucleus using saline. !he anti+E1" assay detects antibodies against the extractable nuclear antigen like Sm, 81? etc. !he nucleolar pattern is caused by the homogeneous staining of the nucleolus. It has been suggested that this antigen be the ribosomal precursor of ribonucleoprotein. !his pattern is most often associated with scleroderma or polymyositis+dermatomyositis. !he centromere pattern only can be seen in dividing cell line. ,ore often it is associated with -8ES! syndrome, which is a special subtype of scleroderma.

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"ntibodies to double+stranded .1" and to Sm are specific for SLE but not sensitive, since they are present in only #$% and ($% of patients respectively. Low levels of anti+ds.1" antibodies may present in normal individuals and in many patients with other diseases. 7owever, a significant titer (which varies with each laboratory) is present only in SLE patients. "nticardiolipin antibodies can be detected and in many cases, it appears to be directed at a serum cofactor ( 9+glycoprotein+I) rather than at phospholipid itself.
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Lupus Band est !LB " Studies of non+lesional skin from patients with SLE show that about half of them have deposits of immunoglobulin and complement proteins at the dermal+ epidermal ;unction. !his is so called Lupus 3and !est. !his is not specific for SLE patient since patients with other rheumatic diseases and skin diseases also may have these granular deposits. It may be of help in the diagnosis of SLE patients whose symptoms are atypical with a negative serum finding. Diagnosis SLE should be suspected in patients with multi+system disease including ;oint pain. !he related symptoms are une&plained fever, purpura, splenomegaly, adenopathy, or aseptic meningitis. !he presence of a single symptom, such as serositis, along with antibodies to double+stranded .1" in a young woman is highly suggestive of SLE. !he '**2 revised criteria for the classification of SLE is listed below. " patient is classified as having SLE if any ) or more of '' criteria are met. Criteria for the classification of SLE. '. ,alar rash 9. .iscoid rash (. ?hotosensitivity ). 0ral ulcers usually less painful 4. "rthritis usually non+difomity #. Serositis 2. 8enal disease a. J $.4 gHd proteinuria, orDb. K (L dipstick proteinuria, orD c. -ellular casts M. 1eurologic disease a. Sei ures, orDb. ?sychosis (without other cause) *. 7ematologic disorders a. 7emolytic anemia, orDb. Leukopenia (N )$$$HOL), orD c. Lymphopenia (N '4$$HOL), orDd. !hrombocytopenia (N '$$,$$$HOL) '$. Immunologic abnormalities a. ?ositive LE cell preparation, orDb. "ntibody to native .1", orDc. "ntibody to Sm, orDd. Balse+positive serologic test for syphilis ''. ?ositive "1" Therapy 5enerally patients need more than normal rest and should be cautioned against sun e&posure. ?rotective lotion may be applied while out of doors. Education and emotional support are important. Stress, including surgery, infections, abortions and psychological pressures may e&acerbate or worsen the disease. Since the various manifestations of idiopathic SLE affect prognosis differently and since SLE activity often wa&es and wanes, drug therapyDboth the choice of agents and the intensity of their useDmust be tailored to match disease severity. " fine balance should be kept between aggressive and prompt treatment and attendant complications brought upon by the therapy itself. Ae may divide the disease activity into ma;or organ involvement and non+ma;or organ involvement.
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,a;or organ involvement includesI glomerulonephritis, central nervous system disease, myocarditis, pneumonitis, thrombocytopenic purpura, hemolytic anemia, severe granulocytopenia and mesenteric vasculitis while non+ma;or organ involvement includesI fever, fatigue, arthritis, myalgia, pleurisy, peritonitis, skin rash, 8aynaudGs phenomenon, mucosal ulcers, lymphadenopathy, and episcleritis. !he management of ma;or organ involvement is usually directed at the preservation of function and prevention of organ failure or death. Intravenous corticosteroids are re6uired in relatively large initial doses, which often e&ceed the dose e6uivalents to 'mgHkg3A prednisone. Steroid psychosis may mimic lupus cerebritis, in which case reduced doses are appropriate. !he dosage of corticosteroids should be individuali ed and depend on the severity of the disease. ?ulse intravenous corticosteroids is controversial. Immunosuppressive agents such as -lophosphamide (-!E), ,ycophenolate mofetil, and "athioprine are used in combination with the corticosteroids. 3oluses of intravenous -!E may be particularly beneficial in lupus nephritis and vascular manifestations of SLE, which improves renal survival. ,ycophenolate mofetil has been shown to be as effective and less to&ic than -!E in the treatment of diffuse proliferative glomerulonephritis. Since -!E is e&creted through kidneys, the doses have to be reduced in case of renal impairment. !he side effects of -!E are substantial. 5astrointestinal irritations are common. "lopecia, bone marrow depression and infections are other notable adverse effects. Long+term use may produce damage to gonadal tissue and lead to ovarian failure and a oospermia. .amage to bladder mucosa may result in hemorrhagic cystitis, bladder fibrosis and transitional cell carcinoma. 5enerous intake of fluids is recommended to reduce these complications. 0ther routine drugs of same family are "F", methotre&ate (,!E) and -yclosporine " (-ys"). " close follow+up is needed to watch for potential side effects when immunosuppressants are given: these agents should be used cautiously and prescribed by e&perienced physicians. Bor patients with the antiphospholipid syndromeDthe presence of antiphospholipid antibodies and compatible clinical eventsDanticoagulation is the treatment of choice. ,oderate intensive anticoagulation with Aarfarin to achieve an I18 of 9.$P(.$ is as effective as more intensive regimens. 1on+ma;or organ involvement does not need aggressive treatment, which is best handled with symptomatic therapy. 8est and 1S"I.s can usually alleviate minor ;oint symptoms. "ntimalarials may be helpful in treating lupus rashes or ;oint symptoms, the doses of which should not e&ceed 94$mgHd for chloro6uine and )$$ mgHd for hydro&ychloro6uine. 3iannual monitoring for retinal changes is recommended. .rug+induced neuropathy and myopathy may be erroneously ascribed to the underlying disease. !o most patients ?,- protocal may be of choice, which is composed of low dose of ?rednisone, ,!E and antimalarials. .ana ol may be effective therapy for thrombocytopenia not responsive to corticosteroids. Course & Prognosise
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!he prognosis for patients with systemic lupus appears to be considerably improved compared to the past as the '$+year survival rates has e&ceeded M4%. It is closely related to the early diagnosis, treatment and long term doctor+patient interaction. Social economic situation is another crucial issue. In most patients, the illness pursues a relapsing and remitting course. Since remission does not e6ual to cure, -orticosteroids should not be 6uit even though the dosage can ultimately be tapered to low doses (4P'$ mgHd). 7owever, there are some in whom the disease pursues a virulent course, leading to serious impairment of vital organs such as lung, heart, brain, or kidney resulting in death. !he mortality and morbidity patterns in lupus have changed. InfectionsDespecially with opportunistic organismsDhave become the leading cause of death, followed by active SLE, chiefly due to renal, cardiovascular disease. "ccelerated atherosclerosis, attributed in part to corticosteroid use, has been responsible for a rise in late deaths due to myocardial infarction. !herefore, it is especially important for SLE patients to avoid smoking and to minimi e other conventional risk factors for atherosclerosis (eg, hypercholesterolemia, hypertension, obesity, and inactivity). Aith 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. Bemale patients who has e&perienced a disease 6uiescent period for more than one year with the steroid administration less than '$mg prednisone or e6uivalent may take consideration for pregnancy. !he escort of low dose steroids is necessary. !he maternal+fetal outcome has been favorable according to the reports of different center.