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The principal goal of therapy in lupus nephritis is to normalize renal function or, at least, to prevent the progressive loss of renal
function. Therapy differs depending on the pathologic lesion. [23, 37] It is important to treat extrarenal manifestations and other
variables that may affect the kidneys.
Corticosteroid therapy should be instituted if the patient has clinically significant renal disease. Use immunosuppressive agents,
particularly cyclophosphamide, azathioprine, or mycophenolate mofetil, if the patient has aggressive proliferative renal lesions,
as they improve the renal outcome. Immunosuppressives can also be used if the patient has an inadequate response or
excessive sensitivity to corticosteroids. [37, 38, 39]
Calcineurin inhibitors, especially tacrolimus, have demonstrated benefit in lupus nephritis. However, most studies have been
limited to Asian patients, and further research is required on long-term benefits and disadvantages. [40, 41, 42]
Treat hypertension aggressively. On the basis of beneficial effects in other nephropathies, angiotensin-converting enzyme
inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) have been routinely used to treat proteinuria in lupus nephritis.
Alter the diet according to the presence of hypertension, hyperlipidemia, and renal insufficiency. Restrict fat intake or use lipid-
lowering therapy such as statins for hyperlipidemia secondary to nephrotic syndrome. Restrict protein intake if renal function is
significantly impaired.
Administer calcium supplementation to prevent osteoporosis if the patient is on long-term corticosteroid therapy, and consider
adding a bisphosphonate (depending on renal function).
Avoid drugs that affect renal function, including nonsteroidal anti-inflammatory drugs (NSAIDs), especially in patients with
elevated creatinine levels. Nonacetylated salicylates can be used to safely treat inflammatory symptoms in patients with renal
disease.
The first guidelines for managing lupus nephritis have been issued by the American College of Rheumatology. [45] Key points of
the guidelines are as follows:
Patients with clinical evidence of active, previously untreated lupus nephritis should have a renal biopsy to classify the
disease according to International Society of Nephrology/Renal Pathology Society criteria
All patients with lupus nephritis should receive background therapy with hydroxychloroquine, unless contraindicated; this
recommendation was based on a prospective controlled trial showing lower flare rates in those who continued
hydroxychloroquine, compared with those who switched to placebo [46]
Glucocorticoids plus either cyclophosphamide intravenously (IV) or mycophenolate mofetil orally for induction in patients
with ISN class III/IV disease; patients with ISN/RPS class I and II nephritis do not require immunosuppressive therapy
Administer ACEIs or ARBs if proteinuria is 0.5 g/24 h or more
Maintain blood pressure at or below 130/80 mm Hg
Joint guidelines for the management of adult and pediatric lupus nephritis have also been issued by European League Against
Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA). The EULAR/ERA-
EDTA recommendations include the following [47] :
Any sign of renal involvement can be an indication for biopsy, which should be performed within the first month after
disease onset, preferably before the institution of immunosuppressive treatment
Use mycophenolate mofetil or or low-dose IV cyclophosphamide plus glucocorticoids as the initial treatment for patients
with ISN class III–IV Adisease
In patients with adverse clinical or histological features, cyclophosphamide can be prescribed at higher doses, while
azathioprine is an alternative for milder cases
For pure class V lupus nephritis LN with nephrotic-range proteinuria, use mycophenolate mofetil in combination with oral
glucocorticoids for initial immunosuppressive therapy
Patients who improve after initial treatment should receive mycophenolate mofetil or azathioprine for at least 3 years;
patients who start on mycophenolate mofetil should continue on that agent
Patients in whom mycophenolate mofetil or cyclophosphamide therapy fails should be switched to the other agent or to
rituximab
Azathioprine can also be used as a second-line agent, with dose adjustments depending on hematologic response.
Mycophenolate mofetil was found to be superior to azathioprine in maintaining control and preventing relapses of lupus
nephritis in patients who have responded to induction therapy. [55]
In a 10-year follow-up of the MAINTAIN Nephritis Trial, which compared azathioprine and mycophenolate mofetil as
maintenance therapy of proliferative lupus nephritis, Tamirou and colleagues found that the two treatments resulted in similar
outcomes. Two deaths and one case of end-stage renal disease developed in the azathioprine group, versus three deaths and
three cases of end-stage renal disease in the mycophenolate mofetil group. [56]
Class V
Patients with membranous lupus nephritis are generally treated with prednisone for 1-3 months, followed by tapering for 1-2
years if a response occurs. If no response occurs, the drug is discontinued. Immunosuppressive drugs are generally not used
unless renal function worsens or a proliferative component is present on renal biopsy samples. Some clinical evidence indicates
that azathioprine, cyclophosphamide, cyclosporine, and chlorambucil are effective in reducing proteinuria. Mycophenolate
mofetil may also be effective.
In a study of membranous lupus nephritis, 38 patients were treated with corticosteroids and azathioprine; after 12 months of
treatment, 67% of patients had a complete remission and 22% had a partial remission, with only 11% resistant to
treatment. [57] Long-term follow-up of 12 years showed 19 episodes of renal flares. Retreatment with corticosteroids and
azathioprine showed similar responses.
NON-SCARRING ALOPECIA
Diffuse thinning or hair fragility with visibly broken hairs, in
the absence of other causes such as alopecia areata, drugs,
iron deficiency, and androgenic alopecia
CLINICAL CRITERIA--LUPUS
SYNOVITIS INVOLVING 2 OR MORE JOINTS
ACUTE CUTANEOUS LUPUS OR SUBACUTE CUTANEOUS Characterized by swelling or effusion
LUPUS OR tenderness in 2 or more joints and at least 30 minutes
Acute cutaneous lupus: lupus malar rash (do not count if of morning stiffness
malar discoid), bullous lupus, toxic epidermal necrolysis SEROSITIS
variant of SLE, maculopapular lupus rash, photosensitive Typical pleurisy for more than 1 day OR pleural effusions
lupus rash (in the absence of dermatomyositis). OR pleural rub
Subacute cutaneous lupus: nonindurated psoriasiform Typical pericardial pain (pain with recumbency improved by
and/or annular polycyclic lesions that resolve without sitting forward) for more than 1 day OR pericardial effusion
scarring, although occasionally with postinflammatory OR pericardial rub OR pericarditis by electrocardiography
dyspigmentation or telangiectasias). In the absence of other causes, such as infection, uremia,
and Dressler’s pericarditis
LUPUS MANAGEMENT - ill patients require education and general prophylactic measures to prevent disease flares:
2- Skin manifestations respond to hydroxychloroquine 400mg/d + topical steroid (hydroxychloroquine is also indicated in
arthralgia resistant to
NSAIDs) .
- Steroids are used for almost all manifestations of lupus in doses ranging from extremely small alternate day doses to huge
pulsed intravenous doses .
- Prolonged steroid therapy usually lead to DM , accelerated atherosclerosis, osteoporosis, glucoma, cataract, avascular necrosis
and increased risk of
infections.
To avoid such toxicities, different cytotoxic drugs can be used to provide steroid sparing effect (see below).
Role of steroids
To control the inflammatory reaction --> prevent end organ damage.
Method
Give full dose of steroid 60-80 mg predinsolone / day till activity of the disease disappears i.e :
* Resolution of symptoms and signs.
* - ve Anti-DNA
* Normal C3 and C4
4- Immunosuppressive drugs
Used in severe disease activity e.g severe lupus nephritis or cerebral disease.
• Azathioprine (Immuran): - 2mg/kg/d orally. It is used when steroid alone is not fully effective. It is also a steroid sparing drug.
i.e it allows
a reduction of steroid dose. The side effects are leucopenia, anaemia & infections.
• Cyclophosphamide (Endoxan):
1-3 mg/kg/d orally, also it can be given as pulse therapy 0.5-1 gm/m Iv.
It is important to monitor the side effects e.g Infections, bone marrow depression and infertility.
This drug is extremely toxic so, it is reserved for the most severe disease manifestations.
• Cyclosporine (Sandimmun) and mycophenolate (myfortic) can also be used with severe disease activity and to avoid the side
effects of other
immunosuppressive drugs.
Pulse steroid therapy can be used in SLE with severe activity. e.g. Vasculitis, cresentic GN, severe cerebral or haematological
disease.
Precautions :
• Prophylaxis for peptic ulceration by proton pump inhibitors.
• Control blood pressure.
• Control blood sugar.
• Isolation to guard against infection.