Rheumatology Case: Seizure in a Patient with Lupus

Given her prior diagnosis of SLE, which seems correct, the differential diagnosis should include lupus-related conditions. The physical examination is very helpful. She has evidence of active lupus with rash, retinopathy, and periungual infarcts. Her current symptoms could be due to CNS vasculitis or cerebritis with encephalopathy and seizures. It is of prime importance to rule out the most serious, treatable conditions immediately, therefore, CNS infections must also be considered in patients with SLE.

Thrombosis or emboli should always be considered in lupus because antiphospholipid antibodies are frequently found in patients with lupus and can be thrombogenic. Her use of oral contraceptives and cigarettes may further increase her risk of thrombosis. Multifocal infarcts from thrombosis or emboli could produce these symptoms. Likewise, given the cardiac murmur, bacterial endocarditis should also be considered since it could cause cerebral emboli and retinal and skin lesions. Abuse of drugs such as cocaine can trigger seizures and the skin infarcts described. The presence of new hypertension and edema suggests hypertensive encephalopathy , which could also be lupus-related.

Lupus-independent conditions such as idiopathic epilepsy would be unlikely to present over this period of time with these physical findings. Similarly, carotid atherosclerotic disease is very unlikely at this young age and would probably not lead to generalized seizures. Migraine, though common in lupus, rarely leads to generalized seizures.

A. Spinal fluid analysis.
B. EEG.
C. Skull x-ray.
D. Brain MRI.
E. PT and PTT.
F. Cerebral angiogram.
G. Drug screen.
H. Echocardiogram.

Systemic infection and CNS infection are the most serious conditions and must be diagnosed immediately so that treatment can be started. Therefore, in addition to the blood cultures already obtained, a spinal fluid analysis for cell count, gram stain, and culture should be done at once. In addition to the CSF analysis and culture, an MRI is indicated to identify an intracerebral space-occupying lesion, hemorrhage, or vasculitis. A PT and PTT are warranted to detect a coagulation disorder that might predispose to CNS bleeding or intravascular clotting (e.g., lupus anticoagulant). A drug screen for cocaine should be done to exclude cocaine-induced seizures and vasculitic lesions. Even though blood cultures were negative, nonbacterial valvular vegetations can develop in SLE (Libman-Sacks endocarditis). An echocardiogram should be done to evaluate the murmur and look for vegetations that could be a source of emboli.

An EEG may be normal or show nonspecific abnormalities and would be unlikely to help in the differential diagnosis. Although cerebral angiography is still used in certain situations, it has generally been supplanted by MRI/MR angiography in the setting of SLE. Skull films might be done even in the absence of a trauma history, but are of low yield.

Anti-dsDNA antibodies are highly specific for SLE, and a high titer with low C3 and C4 levels indicates active disease. Although there is no need to repeat an ANA in a patient with lupus, serial anti-dsDNA antibodies and complement levels are helpful in following patients with renal SLE. A 24-hour urine collection is needed to document the degree of proteinuria and the severity of the patient’s renal insufficiency. Although the PTT is normal, the antiphospholipid syndrome cannot be entirely excluded, because it can result from antibodies specific for cardiolipin, which do not prolong the PTT. In addition, some procoagulant lupus inhibitors are detectable only with methods utilizing multiple substrates in the activated PTT test. Therefore, anticardiolipin antibody and lupus anticoagulant should be ordered in addition to the PTT.

Clinical renal involvement occurs in about 50% of patients with SLE. Serious renal involvement with significant proteinuria and/or renal insufficiency is seen in about 20% of all lupus patients. In patients with nephrotic-range proteinuria, the major differential diagnosis is between diffuse proliferative glomerulonephritis and the less common but more benign membranous lupus nephritis. Since treatment for diffuse lupus nephritis often requires cytotoxic medication in addition to corticosteroids, it is important to distinguish between these two conditions, which requires renal biopsy. Abnormal urinary sediment, low C3 and C4, and very high anti-dsDNA antibody levels would point to diffuse proliferative glomerulonephritis. A renal biopsy would confirm this diagnosis. Activity and chronicity indices, which add to the evaluation of biopsies, have been developed. Some physicians would argue that renal biopsy is not absolutely necessary because testing shows active SLE and is most compatible with diffuse proliferative glomerulonephritis. However, since prognosis and treatment are dependent largely on the nature of the renal involvement, most would recommend renal biopsy in this situation.

Other factors may contribute to renal dysfunction in this patient. For example, NSAIDs can result in clinically significant decreased renal blood flow and cause mild to moderate elevations of serum creatinine. Therefore, ibuprofen should be discontinued, and the serum creatinine and creatinine clearance measured again in four to five days.

Antibody to glomerular basement membrane is a marker for Goodpasture's syndrome. Patients with this disease occasionally present with renal findings alone, as in this case, but usually they also have evidence of pulmonary hemorrhage, with hemoptysis and pulmonary infiltrates. The presence of cANCA is a marker for Wegener's granulomatosis, which would be considered in the differential diagnosis of glomerulonephritis without symptoms of SLE.
Cerebral angiography , renal angiography, and brain biopsy are not indicated at this stage before the results of noninvasive testing are known.

Answer is E

In this patient, high doses of corticosteroids are indicated for initial therapy of active, severe SLE, and given her mental status, parenteral (intravenous) therapy is preferred. Control of seizures is also needed while treatment of acute lupus is initiated. There is good evidence that early treatment of diffuse proliferative glomerulonephritis in SLE with pulse IV cyclophosphamide results in improved survival of both patients and their kidneys. Thus therapy with high-dose corticosteroids, IV cyclophosphamide, and anticonvulsants is the most effective choice for this patient.
Salicylates and low doses of prednisone are suitable for mild cases of SLE, but would not be adequate therapy for severe SLE. Anticonvulsants alone are effective treatment for seizures, but this patient also requires treatment for lupus renal and CNS disease. Intravenous heparin and oral anticoagulants would be indicated in the treatment of patients with lupus who have antiphospholipid antibodies and clinical thromboembolism.

This patient has developed corticosteroid-induced diabetes , emotional lability with insomnia and hyperactivity, and myopathy. A common problem in SLE patients being treated with high doses of corticosteroids is distinguishing steroid side effects, including opportunistic infection, from lupus-related symptoms. The side effects occur much more frequently and severely when prednisone doses are greater than 20 mg/day. The important side effects that can lead to diagnostic confusion include CNS effects with insomnia, hypomania, mood swings, and frank psychosis; induction or exacerbation of diabetes mellitus; myopathy with proximal muscle weakness; and avascular necrosis of the hips and knees.

This patient's symptoms are most likely due to steroid side effects rather than worsening SLE , given her improvement in renal function, proteinuria, and serologic values, including anti-dsDNA titers and C3 and C4 levels. There is nothing to suggest systemic infection or renal vein thrombosis. Therefore, the treatment of choice is to give insulin for the diabetes and lower the steroid dose as quickly as possible. An advantage of the early use of a cytotoxic agent such as cyclophosphamide is the potential for a more rapid reduction of the corticosteroid dose.