A 21-year-old female of mixed heritage (Caucasian and African American), with a history of provoked deep venous thrombosis diagnosed six months before, currently treated with warfarin, presented with complaints of acute chest pain. The pain was midsternal, severe, sharp, and worse with inspiration but improved by sitting upright. Vital signs revealed tachycardia (154 beats per minute), tachypnea (30 breaths per minute), and normal blood pressure (136/73 mmHg). The INR was 5.4 on admission. The chest X-ray showed cardiomegaly with a bottle neck sign. The echocardiogram showed a large pericardial effusion, with evidence of right-sided collapse during diastole. Chest, abdomen, and pelvis CT demonstrated a large pericardial effusion, consistent with hemorrhage. There were no pulmonary emboli or signs of pulmonary hemorrhage. The patient was transfused plasma and blood with improvement of the INR to 2.1. Pericardiocentesis was performed with a return of 500 cc of bloody fluid, and a drain was placed. Her vital signs improved and symptoms diminished immediately after the procedure.
She was diagnosed with underlying pericarditis with effusion that converted to a hemorrhage from the anticoagulation. The etiology of her pericarditis was sought. She denied any recent viral illnesses, tuberculosis exposure, malignancy, or fungal infections. She denied any arthritis, oral ulcers, fever, weight loss, night sweats, rash, or family history of autoimmune disease. Pericardial fluid was sent for cytology as well as viral, fungal, aerobic, anaerobic, and AFB cultures that were all negative. No autoimmune testing was performed on the pericardial fluid. Initial laboratory work revealed normal electrolyte panel and renal function and BNP 59 pg/ml (0-100). She had mildly elevated liver function tests with AST 69 U/L (10-37) and ALT 52 U/L (8-37). She was also found to have normocytic anemia. The hemoglobin was 9 g/dl (baseline was 11.1) with a normal white blood cell and platelet count. Inflammatory markers were elevated: erythrocyte sedimentation rate was 35 mm/hr (0-18), C-reactive protein was 10.4 mg/dl (0-0.8), and ferritin was 314 ng/ml (12-207).
Autoimmune evaluation showed an ANA titer of 1 : 1280 with speckled pattern and markedly elevated anti-double-stranded DNA 195 IU/ml (<100). SSA Ab and SSB Ab were also elevated at 187 and 538 AU/ml (<100), respectively. The patient did not have any clinical symptoms to suggest sicca syndrome (no dry eyes or mouth). TSH on admission was 0.60 (0.5-5.20 mcIU/ml) with repeat serial TSH remaining in normal limits. Clinically, she was never symptomatic with thyroiditis. Complement C4 was low at 7 mg/dl (12-43). Rheumatoid factor was 27 IU/ml (0-14). ANCA, SPEP, CCP, anti-Smith Ab, RNP Ab, and complement C3 were normal. Initial antiphospholipid screen (APS) was positive; however, repeat testing approximately 12 weeks later was negative. Initial APS enzyme-linked immunosorbent assay (ELISA) showed anti-cardiolipin Ab IgA < 9.5 (<12 APL), IgG 21.6 (<15 GPL), IgM 19.7 (<12.5 MPL), beta-2 glycoprotein 1 IgG 12.1 (<20 SUG), and beta-2 glycoprotein I IgM 24.5 (<20 SMU). Repeat APS panel was negative with all results at <9.5. DRVVT screen was 50 (0-52 seconds). The patient was determined to not have antiphospholipid syndrome due to lack of positive repeat APS Ab blood work. Infectious work-up including VDRL, HIV, pericardial fluid Gram-stain, culture, AFB stain and culture, and virus culture was negative. Pericardial fluid cytology was negative for malignancy and revealed increased neutrophils and lymphocytes.
The patient was diagnosed with systemic lupus erythematosus and was started on intravenous (IV) methylprednisolone 100 mg for 3 days with transition to prednisone 40 mg daily, hydroxychloroquine 200 mg twice daily, and colchicine 0.6 mg twice daily. She was also treated with ibuprofen 400 mg every 6 hours and opioids for pain control. Over the next 48 hours, an additional 120 cc bloody fluid was drained after repositioning the pericardial drain, which was then successfully removed. In hospital day 3, troponin peaked at 3.09 ng/dl (0-0.05) and lupus myocarditis was considered. A cardiac MRI showed normal LV function and no evidence of myocarditis. However, it did reveal severe diffuse, circumferential pericardial contrast uptake involving both the visceral and parietal pericardium with trivial pericardial effusion. She continued to improve and was discharged after 8 days from the hospital with colchicine 0.6 mg twice daily, hydroxychloroquine 200 mg daily, and prednisone 40 mg daily. Colchicine was used to treat the patient for inflammatory pericarditis as imaging revealed inflammation, and she remained symptomatic despite evacuation of pericardial fluid.
Three weeks later, she presented with recurrent chest pain despite compliance with her medications. ECG showed new T-wave inversions in multiple leads and troponin peaked at 4 ng/dl (0-0.05). BNP was elevated at 742 pg/ml (0-100). A transesophageal echocardiogram showed an ejection fraction of 45% with mild-moderate mitral regurgitation. A cardiac MRI showed midmyocardial and epicardial hyperenhancement in the midlateral and inferolateral walls, suggestive of myocarditis. It also revealed persistent pericarditis similar to prior cardiac MRI but no pericardial effusion or constriction. Myocardial perfusion imaging showed fixed radiotracer defect in the mid-distal inferior and inferolateral walls concerning for myocardial scar. PET Myocardial Perfusion and Viability study showed resting hypoperfusion in the midinferior lateral region, which was matched on FDG suspected to be scar formation and flow-metabolic mismatch in the basal inferior and basal inferolateral regions, approximating 12% of the left ventricle. The myocardial scar was estimated to be 6% of the left ventricle myocardium. She was started on aspirin and carvedilol 3.125 mg twice daily. She was again treated with IV steroids and started on azathioprine 50 mg twice daily. Repeat anti-double-stranded DNA had decreased to 130 IU/ml (<100); however, complements C3 and C4 remained low at 76 mg/dl (80-200) and <6 mg/dl (12-43), respectively. Her symptoms improved, and she was discharged home after 6 days from the hospital.
Six weeks later, she presented to the hospital again with recurring chest pain that was associated with bilateral leg swelling, dyspnea with exertion, and orthopnea. BNP was markedly elevated at 1098 pg/ml (0-100). Transesophageal echocardiogram also revealed EF 35% with left ventricular global hypokinesis and moderate-severe mitral regurgitation. Infectious endocarditis was ruled out with serial blood cultures, and no vegetations were found on imaging. A third cardiac MRI was performed which showed a severely depressed ejection fraction 29% and midinferolateral wall akinesis with full thickness hyperenhancement. When compared to the prior MRI, it also showed progression of her myopericarditis.
Cardiac catheterization showed normal coronary arteries, ejection fraction 25%, global hypokinesis, and severe +4 mitral regurgitation with severely enlarged left atrium. Cardiovascular surgery was consulted regarding evaluation for mitral valve repair; however, recommendations were made to pursue surgery only if she were to fail maximum medical treatment. Given no recommendations for surgery, invasive myocardial biopsy was deferred as well. She was treated for acute decompensated congestive heart failure with IV furosemide, and later adequate diuresis was transitioned to oral furosemide 20 mg daily. She was also started on spironolactone 25 mg daily, carvedilol 6.25 mg twice daily, and lisinopril 5 mg daily.
Interestingly, a repeat anti-double-stranded DNA was normal at 83 IU/ml (<100); however, complement C4 remained low at 6 mg/dl (12-43). Given progression of her disease despite medication compliance, she was treated with 1 gram IV methylprednisolone for 3 days along with IVIG for 2 days. She was continued on hydroxychloroquine sulfate 200 mg twice daily and colchicine. Azathioprine was eventually discontinued and changed to mycophenolate mofetil 500 mg twice daily with plans to increase to 1000 mg twice daily.
She was monitored by serial echocardiograms which showed stabilization and mild improvement in her valve function. She was then discharged home after 12 days from the hospital. Repeat PET Myocardial Perfusion and Viability study performed 3 weeks later (and 4 months after initial presentation) showed similar findings to a prior study with active inflammation of the basal inferior, and basal inferior lateral regions were estimated to be 12% of the left ventricle myocardium. Myocardial scar/fibrosis was estimated to be 8% of the left ventricle myocardium. She was then started on cyclophosphamide with repeat echocardiogram showing improvement in ejection fraction to 36% and mild-moderate mitral regurgitation and complement levels improving. Fortunately, her most recent echocardiogram (2.5 years after initial diagnosis) reveals an EF of 55%, mild mitral regurgitation, and no hypokinesis appreciated. Her complement levels and anti-double-stranded DNA remain within normal range and no other manifestations of SLE. Unfortunately, due to prolonged, high-dose steroid use for over 1 year, she developed avascular necrosis of her bilateral femoral heads and condyles necessitating surgery on her bilateral knees and hip. Currently, her only immunosuppressive medication remains hydroxychloroquine.