A complex disorder of multifactorial origin resulting from interactions among genetic, hormonal and environmental factors acting in concert to cause activation of helper T cells and B cells that results in the secretion of several species of autoantibodies.
In this complex web, each factor may be necessary but not enough for the clinical expression of the disease; the relative importance of various factors may vary from individual to individual.
Fixed erythema, flat or raised, over malar eminences, tending to spare nasolabial folds Erythematous raised patches of adherent keratotic scaling and follicular plugging. Atrophic scarring may be seen in older lesions. Skin rash as a result of unusual reaction to sunlight (UV rays) Oral or nasopharyngeal ulcers, usually painless, observed by a physician Non-erosive arthritis involving 2 or more peripheral joints, characterised by tenderness, swelling or effusion Pleuritis – pleuritic pain, rub heard or pleural effusion, or, Pericarditis – documented by ECG or rub or pericardial effusion Persistent proteinuria > 0.5g/day not > 3+. Cellular casts: red cell, haemoglobin, granular, tubular or mixed. Seizures or psychosis in the absence of offending drugs or metabolic derangement. Haemolytic anaemia with reticulocytes, or: Leucopenia < 4000/mm 3 on 2 or more occassions, or: Lymphopenia <1500/mm 3 on 2 or more occasions, or: Thrombocytopenia<100000/mm 3 in absence of offending drugs Anti-DNA antibody, or: Anti-Sm antibody, or: Anti-phospholipid antibodies: i. abnormal anticardiolipin antibody IgG or IgM; ii. Positive lupus anticoagulant; iii. False positive for syphilis for > 6 months Abnormal titre of ANA at any point in absence of drugs known to be associated with drug induced lupus 4 out of 11 criteria gives a 96% sensitivity and 96% specificity for SLE. Criteria do not all have to be present at a defined time and can be cumulative.
Any patient with SLE who has clinical or laboratory evidence of active nephritis, especially with the first episode of nephritis
Patients with recurrent episodes of nephritis
TO GUIDE TREATMENT ON USE OF POTENTIALLY TOXIC DRUGS TO PREDICT OUTCOME
International Society of Nephrology 2003 classification of lupus nephritis Chronic lesions and sclerosis Advanced sclerosing Class VI Predominantly nephrotic disease Membranous Class V >50% of glomeruli involved Diffuse proliferative Class IV <50% of glomeruli involved Focal proliferative Class III Hypercellular on light microscopy Mesangial proliferative Class II Normal light microscopy findings, abnormal electron microscopy findings Minimal mesangial Class I
Class I: Minimal mesangial lupus nephritis require no specific therapy.
Class II: Mesangial proliferative lupus nephritis may require treatment if proteinuria is greater than 1000 mg/d. Consider prednisone in low-to-moderate doses (ie, 20-40 mg/d) for 1-3 months, with subsequent taper.
Classes III and IV: Patients with either focal or diffuse lupus nephritis are at high risk of progressing to end-stage renal disease and require aggressive therapy.
Administer prednisone 1 mg/kg/d for at least 4 weeks, depending on clinical response. Then, taper it gradually to a daily maintenance dose of 5-10 mg/d for approximately 2 years. In acutely ill patients, intravenous methylprednisolone of up to 1000 mg/d for 3 days may be used to initiate corticosteroid therapy.
Both cyclophosphamide and azathioprine are effective for proliferative lupus nephritis, although cyclophosphamide is apparently more effective in preventing progression to end-stage renal disease.
Administer iv cyclophosphamide monthly for 6 months and every 2-3 months thereafter, depending on clinical response. The usual duration of therapy is 2-2.5 years. Reduce the dose if the creatinine clearance is less than 30 mL/min. Adjust the dose depending on the hematologic response. Gonadotropin-releasing hormone analog, leuprolide acetate, protects against ovarian failure.
Azathioprine can also be used as a second-line agent , with dose adjustments depending on hematologic response.
Mycophenolate mofetil is useful in patients with focal or diffuse lupus nephritis and has been to be at least effective as iv cyclophosphamide with less toxicity in patients with stable renal function . Can be used alone or sequentially after a 6-month course of iv cyclophosphamide.
SLE is a potentially life-threatening disease, however pts can do well if the disease is recognized early and treated aggressively.
Renal disease is a major cause of morbidity and mortality in children with SLE.
The short and long term outcome have improved in recent years.
As pts survive longer, there is significant morbidity from the disease and its treatments and it is difficult to balance minimising permanent organ damage with side effects from potentially harmful drugs.