A 15-year-old previously healthy South Asian, Sri Lankan female presented with three episodes of generalized tonic clonic seizures over a 24-h period, which progressed to status epilepticus within 2 h of admission. A targeted history from observer and family member revealed that she had developed an erythematous painless rash over both legs that had progressed over the preceding 2 weeks prior to the presentation. Furthermore, she also had a headache for 2 days, which had been diffuse in nature without features favoring meningism, discernible systemic symptoms, or fever to suggest an association or etiology. There was no background history of autoimmune diseases. The patient and family failed to recognize the clinical significance and did not seek medical intervention when these symptoms had occurred.
On examination, she was afebrile. She had mild periorbital edema and a resolving purpuric rash was noted on both her ankles. Despite a detailed neurological examination, no focal neurological signs were demonstrable. The fundi were also normal with no papilledema. Examination of her cardiovascular system revealed her blood pressure to be within reference range; however, a tachycardia was noted, though it was regular in rhythm. The jugular venous pressure was however elevated. Auscultation revealed a grade 2 pan-systolic murmur at the apex, favoring a mitral regurgitation, but the apex was not shifted. Respiratory system examination revealed tachypnea and presence of bibasal lung crepitations, in the absence of other features. Abdominal examination failed to reveal clinically significant findings.
In view of her seizures and status epilepticus, she was treated with intravenous diazepam 10 mg followed by intravenous phenytoin 18 mg/kg bolus along with oral sodium valproate via a nasogastric tube, which failed to control seizures. She was therefore electively intubated and ventilated while inducing paralysis and was started on intravenous midazolam followed by thiopentone sodium.
Capillary blood sugar values and serum electrolytes were within normal reference range. All basic investigations including blood counts, biochemistry, and cultures were done along with a lumbar puncture. Erring on the side of caution, she was empirically treated with intravenous ceftriaxone and intravenous acyclovir along with intravenous dexamethasone to cover the possible spectrum of meningoencephalitis.
While on treatment for possible meningoencephalitis, her clinical picture deteriorated; her tachycardia worsened and desaturated on atmospheric oxygen. Worsening signs of heart failure alerted us to the possibility of myocarditis. Electrocardiogram showed sinus tachycardia with T wave inversions in chest leads V2 to V6. Despite this, her cardiac enzyme assay (Troponin T and I, CK- MB) was negative. Her chest x-ray revealed relative cardiomegaly. Transthoracic 2D-echocardiohraphy (Phillips EQIP CVx, made in Germany) revealed moderate left ventricular systolic dysfunction with an ejection fraction of 40% with left ventricular global hypokinesia, along with a grade 2 severity mitral regurgitation, grade 1 severity aortic regurgitation; a clinically insignificant thin rim of pericardial effusion with no right atrial or ventricular collapse was noted. Following a cardiac consult, a clinical decision was taken to manage her medically with diuretics and fluid restriction. Upon stabilization, she was started on bisoprolol 2.5 mg bd and ivabradine 2.5 mg daily for control of heart rate along with a low dose enalapril of 2.5 mg daily.
Upon clinical recovery from status epilepticus and cardiomyopathy, while still under investigation, we noted a trend toward reduction in cell counts in her whole blood analysis. Pancytopenia was seen on day 14 of her presentation. Hemoglobin dropped from 12.4 to 8.2 g/dL, while the total white blood cell count (WBC) was noted to have reduced to 3.5 x 109/L (4-10) with a differential count suggestive of neutropenia (2.8 x 109/L) and a lymphocyte count of 0.35 x 109/L. Thrombocytopenia was also noted. Blood picture revealed few fragmented red blood cells (RBC) with the lactate dehydrogenase elevated at 851 U/L (225-450). Coomb's test was negative. Ongoing inflammation was appreciated, as the C-reactive protein was initially elevated at 60 mg/l (< 5), which then decreased to 8 mg/l (< 5). The erythrocyte sedimentation rate (ESR) also rose from 22 mm in the first hour, to reach 50 mm later in the second week of her presentation. Her coagulation profile (prothrombin time/international normalized ratio, activated partial thromboplastin time and plasma fibrinogen, renal and thyroid function tests, and liver profile) were all normal (Table 1). 
In suspecting a multisystem disease, three urinalysis reports done within the first 2 weeks repeatedly showed moderately field full RBC in a high power field with 40% dysmorphic RBC, red cell casts, and WBC (25-30 cells/per high power field). Despite this, her urine culture was sterile. She also had a sub-nephrotic proteinuria (600 mg of protein for 24 h). Ionized calcium and serum magnesium were repeatedly marginally below the reference value with normal urinary excretion of calcium and magnesium. Serum parathyroid hormone level was also normal (Table 1).Vitamin B12 levels were normal at 273 pmol/L (140-650).
Extensive neurological investigations were carried out. Non-contrast CT brain was suggestive of mild cerebral edema. Magnetic resonance imaging with T2 flair image showed very subtle altered signal intensity in bilateral parietal and occipital regions, suggesting acute parenchymal inflammatory changes favoring encephalitis. The cerebrospinal fluid (CSF) analysis showed isolated high levels of protein (387 mg/dL) in the absence of leucocytes and red blood cells. CSF for gram stain, culture, Ziehl-Neelsen stain, polymerase chain reaction (PCR) for mycobacterium tuberculosis, tuberculosis culture, herpes simplex virus 1 PCR, Japanese encephalitis IgM antibodies, anti-NMDA (N-methyl d-aspartate) and receptor antibodies were all negative. Electroencephalogram revealed only diffuse slow waves.
Cultures of blood, endotracheal secretions, and urine were sterile. Leptospirosis serology (microscopic agglutination test for leptospirosis), Rickettsia serology, viral studies for HIV (human immunodeficiency virus antigen and antibody), JE (Japanese encephalitis antibodies IgG and Ig M), EBV (Epstein-Barr virus monospot and antibody test), CMV (Cytomegalovirus IgG, IgM, and PCR), and dengue were all negative.
On suspicion of connective tissue disease, anti nuclear antibodies (ANA) were done and was found to be weakly positive (1: 40) (Method used: indirect immunofluorescence assay, Substrate used HEp 2 cells). Anti dsDNA showed positivity with very high titers of > 150 IU/mL. (Positive if > 46.1 in method used ELISA, confirmed by IFA). Human complement 3 (C3) and human complement 4 (C4) were both low: C3 = 41 mg/dL (83-177), C4 = 03 mg/dL (12-36). Anti cardiolipin antibody, anti-beta 2 glycoprotein antibody, and lupus anticoagulant were negative.
Intravenous antibiotics and antivirals were ceased with negative cultures and a working diagnosis of SLE was made. Heart failure treatment was continued till she showed clinical and echocardiographic recovery. Sodium valproate was continued at a dose of 200 mg tds while phenytoin infusion was tailed off gradually. By day 14, she had recovered back to her premorbid state with complete recovery from both her neurological and cardiac conditions. Serial ECHOs were done and by day 14 the left ventricular ejection fraction had improved back to 60% with no regional wall motion abnormalities. She was discharged on day 21, on sodium valproate and folic acid with a follow up review planned by the multidisciplinary team. A repeated urinalysis on the day 21 only showed few RBC and WBC. The urine protein creatinine ratio was marginally elevated at 0.5 (< 0.4). Because of the resolving microscopic hematuria and proteinuria, renal biopsy was not done during the current admission. A repeated ANA done on day 28 was high (1/320) and the dsDNA too was elevated at 81.7 IU/mL.