Case: A 12 year female child presented with history of fever for 1 month & shortness of breath with decreased urine output for 2 days. The child was in congestive cardiac failure. A diagnostic work up including complete blood count, blood biochemistry, culture sensitivity, serological markers of infection, immunological markers, chest X-ray and 2D echocardiography were performed to determine the etiology of her symptoms and to differentiate infective and non infective causes of fever with heart failure.
All Infective causes of fever with heart failure were ruled out. Finally in view of raised anti nuclear antibody and anti double stranded DNA a diagnosis of Systemic Lupus Erythematosus was made. Echocardiography showed evidence of Libman- Sacks endocarditis. Unfortunately the child expired despite treatment with antibiotic, immunosuppressives and anticoagulants.
This case provides the challenges in making the correct diagnosis when two disease processes present with similar findings.
Key words :
Anti nuclear antibody, anti double stranded DNA, Systemic Lupus Erythematosus, Libman- Sacks endocarditis.
Libman - Sacks endocarditis is a form of non bacterial endocarditis that is seen in Systemic Lupus Erythematosus. It was first decribed by Dr. Emanuel Libman and Benjamin Sacks at Mount Sinai Hospital in New York in 1924. Endocarditis and antiphospholipid syndrome was first noticed in 1985. The characteristics of Libman- Sack endocarditis were reported in postmortem studies in about 50% of fatal cases of systemic lupus erythematosus.
Case history :
A 12 year old female child presented at the emergency room with a history of low grade irregular fever for 1 month & respiratory distress gradually increasing in severity for 2 days. It was associated with history of swelling of feet and diminished urine output. There was no history of any congenital heart disease, joint pain and rash, bleeding manifestations, loss of consciousness or convulsions. She was being treated in a local hospital (records of which were not available) but there were no improvement.
Examination revealed an alert conscious febrile (axillary temperature 1010F) child with tachypnoea (respiratory rate 40/min.) & tachycardia (pulse rate 120/min., regular). She had severe pallor with extensive oral thrush and bilateral pitting pedal edema. Her blood pressure was 90/60 mm of Hg. Neck veins were engorged, pulsatile and jugular venous pressure was raised. Examination of the cardiovascular system showed cardiomegaly with grade 3/6 holosystolic murmur best heard in the lower left sternal border radiating to the axilla and a gallop (S3) was also audible. On chest examination there were bilateral basal crepitations. There was an enlarged soft tender liver with mild splenomegaly. There was no associated lymphadenopathy, clubbing, haemorrhagic manifestations, sensory or motor neurodeficit.
As the child was in congestive cardiac failure she was immediately shifted to intensive cardiac care unit. Initial laboratory investigations showed a hemoglobin level of 4gm/dl, total leucocyte count 18500/mm3 (80% neutrophil & 18% lymphocytes), platlet count 50000/mm3, erythrocyte sedimentation rate (ESR) 128mm 1st hour, C-reactive protein (CRP) 54mg/dl (Normal < 6mg/dl.), antistreptolysin O (ASO) titre 350. Blood biochemistry and liver function tests were within normal limits. Preliminary urine analysis showed microscopic hematuria with granular cast.
Considering congestive cardiac failure in a 12 year old child, (from a low socio economic background) a diagnosis of rheumatic heart disease was made. Chest X-ray showed cardiomegaly. 2D echocardiography showed ejection fraction 30% and vegetations in the ventricular side of the posterior mitral leaflet of the mitral valve. Thinking it to be a case of rheumatic heart disease with possible infective endocarditis (modified Dukes criteria: 1major criteria vegetation in echocardiography and 2 minor criteria - fever, evidence of immunological phenomenon - microscopic hematuria and granular cast) the child was put on intravenous antibiotics ceftrioxone with gentamycin along with decongestive therapy. But even after 48 hours fever continued and the child did not show any improvement. By this time she had developed serositis. 3 consecutive blood cultures from 3 different sites at 30 minutes interval proved to be sterile. Serological markers for infective etiology hepatitis B surface antigen (Hbs Ag), HIV screening, Widal tests were also negative. Thinking of a non infective inflammatory etiology, immunological markers were sent. Anti nuclear antibody (ANA by indirect immunofluorescence) was positive in 1: 234 dilution, anti double stranded DNA (anti dsDNA) was raised (1920), anti phospholipid antibodies were positive. INR was 3.
So the diagnosis was revised. The 12 year female child presented with fever and congestive cardiac failure without any proven infective etiology. Considering raised immunological markers and positive antiphospholipid antibodies, a diagnosis of Systemic Lupus Erythematosus (SLE) with Libman- Sacks endocarditis was made. The child was put on immunosuppresives -- intravenous methyl prednisolone with cyclophosphomide and anticoagulation with warfarin were started. Within 48 hours congestive cardiac failure was controlled and fever gradually subsided. Unfortunately on day 5 of admission the child developed status epilepticus and inspite of aggressive anticonvulsant therapy she succumbed.
Prognosis of patients with SLE depends on the underlying organ involvement- mainly renal and myocardial involvement. Libman - Sacks endocarditis is noted in >10% (by transthoracic echocardiography) and upto 30% (by trans esophageal Echo cardiography) of SLE patients. Of this mitral regurgitation is commonest followed by aortic regurgitation[5-6]. About 41% cases with SLE with valvular involvement have antiphospholipid antibodies[7-8]. Increased titre of antiphospholipid antibodies is associated with severe valvular damage. Though significant occurrence of embolic phenomenon due to antiphospholipid antibodies is quite low. In our case it may have caused the sudden onset of convulsions which let to the death of the child. Because of the occurrence of infective endocarditis in patients with persistent Libman- Sacks endocarditis is not uncommon, it is very important to differentiate between the 2 conditions, as the management is different.
Modified Dukes criteria utilizing pathological and clinical criteria can be useful in differentiating between the 2 conditions. Patients of definite infective endocardits have 2 major or 1 major and 3 minor criteria or 5 minor criteria while patients with probable infective endocardits have 1 major and 1 minor criteria or 3 minor criteria. Major criteria include demonstrations of typical micro organisms from 2 separate sites of blood cultures and endocardial involvement evidenced by positive echocardiography or new valvular regurgitation. Minor criteria include predisposing heart condition or injecting drug use, fever > 100.40F, vascular and immunological phenomenon, micro biological evidence with blood cultures not meeting major criteria or serological evidence of active infection with organisms consistent with infective endocardits. Our patients had 1 major and 2 minor criteria. Some authors suggest that certain laboratory tests may be useful in differentiating the 2 conditions -
1) WBC count - usually low in a lupus flare.
2) CRP level - usually low in a lupus flare.
3) Antiphospholipid Antibodies if levels are high it is more suggestive of lupus[7-8]. Infective endocardits vegetations are likely to be noted at the leaflets line of closure, homogenous in echogenicity and may show a vibratory motion. In contrast vegetations of Libman - Sack endocarditis are located at basal, middle or tip of leaflets on the atrial side of mitral valve or vessel side of aortic valve, heterogenous and of variable size. The prominent finding is valvular thickening.
As medical therapy improves, clinicians should expect to see Systemic Lupus Erythematosus patients live longer and develop a more chronic picture over time. At times infective causes can closely mimic noninfective inflammatory lesions in systemic lupus erythematosus leading to misdirected treatment and fatal outcomes. In tropical countries like India where rheumatic heart disease is very much prevalent noninfective endocarditis may be overlooked and may be misdiagnosed as rheumatic carditis or infective endocarditis which should be kept in mind to avoid fatal outcome.
Our patient was only 12 years old and had a high titre of antiphospholipid antibodies which might have predisposed to embolic manifestations. Clinicians treating any child with fever and congestive cardiac failure without any prior congenital or rheumatic heart disease should also keep in mind non infective inflammatory causes. Prompt and appropriate treatment can save a child.