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51 Lupus Flare How
51 Lupus Flare How
INTRODUCTION
PATHOGENESIS
SLE is characterized by abnormal immune response due
to persistence of pathogenic B and T cells in genetically
282 Medicine Update-2011
know the clinical features of SLE (Table I). During flare, Clinically relevant lupus nephritis is associated with a 30%
organ system may be involved singly or in combination. decrease in creatinine clearance, proteinuria of greater than
The onset may be acute or insidious. The symptoms may 1000 mg/d, and renal biopsy findings indicating active lupus
be non-specific constitutional or specific for the organ nephritis. Anti-nucleosome antibodies appear early in the
system involved.Arthalgia, fever and rash are the common course of the autoimmune response in SLE. They have high
presenting features. sensitivity and specificity for the diagnosis of SLE, and the
titers correlate with disease activity. Anti-C1q antibodies
Immunological profile in lupus flares are associated with lupus nephritis; higher titers correlate
Disease activity can be evaluated with anti-dsDNA, with active renal disease.
complement determinations (C3, C4, and CH 50), and
erythrocyte sedimentation rate (ESR) .Generally, an Systemic Lupus Erythematosus Disease Activity Index1
elevated ESR and anti-dsDNA and low C3, C4 levels are (SLEDAI-Table II) scores correlate with the clinician’s
associated with active disease, especially lupus nephritis. impression of level of disease activity.
events. Pericarditis
Demyelination, transverse myelopathy, chorea: These Arthritis
are rare manifestations. Incidence is 1-3%. Transverse Renal
myelopathy and chorea present as acute manifestations and Vasculitis
have strong association with APLA. Transverse myeopathy
is almost always secondary to vascular occlusion. Sensory Frequency of flares in pregnancy4
motor neuropathy has incidence upto 28%. 1st trimester-13.3%
2nd trimester-40%
DIAGNOSTIC IMAGING FOR C.N.S. FLARE 3rd trimester-13.3%
C.T. - Only for acute cerebral hemorrhage. Post partum-33.3%
MRI - T2 weighted images identify edema. Fixed lesions in
paraventricular and sub cortical white matter within the Pregnancy in patients with SLE should not be regarded as an
territory of major cerebral blood vessel may be found. unacceptable high risk condition provided that conception is
Diffuse sub cortical white matter lesions and patchy hyper accurately planned and patients are managed with a careful
intensities in gray matter may be found. Other lesions may multidisciplinary treatment schedule. Flares usually occur
be venous thrombosis and increase signals in spinal cord. during the last half of pregnancy and within the first few
MR Spectroscopy - Allows identification and quantification of weeks after delivery .The patients should hence be carefully
brain metabolites. It gives an indirect assessment of cellular monitored during this period (Table III). The presence of
changes. Neurocognitive dysfunction is associated with APLA increases the risk for miscarriages.5 Lupus antibodies
reduced N-acetyl levels. Brain lactate levels are increased can be transferred from the mother to the fetus and result in
indicating ischemic inflammation. Choline compounds are neonatal lupus. Problems can also develop in the conducting
increased reflecting damaged cell membranes and myelin system of the heart (congenital heart block). Women
destruction. pregnant and known to have the antibodies for anti-Ro (SSA)
or anti-La (SSB) should have frequent echocardiograms to
Biologic markers in CSF monitor fetal heart and surrounding vasculature.
Pleocytosis.
Elevated proteins. Monitoring SLE flare
Elevated neurofilament triplet protein- 74% sensitive, 65% 1. Watch for clinical signs and symptoms
specific. 2. Hematological tests
CSF- Gilal fibrillary acidic protein (GFAP) - 48% sensitive, 87% 3. Biochemical tests
specific.GFAP levels are associated with MRI abnormalities 4. Immunological tests (Table IV)
and decreased following therapy with cyclophosphamide. 5. Specific organ system monitoring
Every SLE patient may have subclinical CNS involvement 6. Imaging
which can flare to any bizarre clinical picture. A clinical
suspicion and appropriate imaging (PET scan, angiography, TREATMENT OF S.L.E. FLARE
MRI) should be instituted early. Arthritis and cutaneous flare
Acute severe joint pain should initially be treated with short
Myositis course NSAIDs.Animalarials are particularly useful for arthritis
During lupus exacerbations, myositis with muscle tenderness and cutaneous manifestations of SLE. These agents have
and proximal muscle weakness is common. It occurs in multiple properties: immunosuppressive, anti-inflammatory
~10% patients. Raised CPK, aldolase and EMG do not help and sun-blocking. They are also reported to possess anti-
to differentiate other inflammatory myopathies from lupus platelet and cholesterol lowering effects. The drug of
myositis. At times, normal enzymes may be found. A muscle choice is hydroxychloroquine (200 mg BD for 3 months and
biopsy is required in such cases. then 200 mg daily). The maintenance dose must not exceed
6 mg/kg/day. Although the incidence of retinal toxicity is
Effect of pregnancy on SLE flares very low, annual monitoring of vision is recommended (for
The types of flares can be as follows: chloroquine, 6-monthly monitoring is desirable). Topical
Cutaneous sunscreens with SPF of atleast >15 should be applied on
Hematological (thrombocytopenia) exposed parts. In non-responders, low dose corticosteroids
Medicine Update-2011 285
Table III: Laboratory monitoring in pregnancy and antiphospholipid syndrome with lupus flare
or methotrexate or leflunomide should be added. induce a complete or partial remission in more than 80%
Renal flare of patients with proliferative lupus nephritis.Azathioprine
Reduction of proteinuria with angiotensin converting or mycophenolate with low dose steroids can be used
enzyme (ACE) inhibitors delays and prevents renal sclerosis. for maintenance. Rituximab, a B-lymphocyte- depleting
A combination of ACE inhibitors and angiotensin receptor therapy, appears to be effective in SLE and is being used for
blockers reduce proteinuria by ~50%.Spironolactone also SLE and lupus nephritis.8 Statins are indicated in patients
helps to reduce proteinuria.Eplerenone can be used in men with nephrotic syndrome and patients who have developed
because of its low risk of causing gynaecomastia. steroid induced hyperlipidemia. Besides lipid lowering,
they have anti inflammatory properties. They are useful in
Mycophenolate mofetil is the preferred medication for reducing the incidence of inflammatory and steroid related
induction in active nephritis because of its therapeutic atherosclerosis in SLE.
equivalence with Cyclophosphamide (CYC) and lower
rates of adverse events.6 The standard regimen of CYC CNS flare
or mycophenolate with corticosteroids still remains the Important step is to determine whether the event can be
best option to preserve renal function in patients with convincingly attributed to SLE. Low hemoglobin, high ESR,
proliferative lupus nephritis.7 Solid evidence shows that low C3, C4 levels, rising titers of dsDNA indicate a flare.
this drug combination administered either traditionally CSF study to rule out infections such as tuberculosis and
(corticosteroid and monthly pulse CYC) or in modified India ink preparation for fungi is the next important step.
regimen (smaller doses of CYC given at weekly or Methyl prednisolone 1 gm IV daily for 3 days followed by IV
fortnightly intervals over a short treatment duration) can cyclophosphomide 1 gm on 4th day is a standard protocol
286 Medicine Update-2011
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Exp Rheumatol 1999 Jul-Aug; 17(4): 467-70 Nephron clin Pract 2005; 100(3):c92-100.
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