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Indian Pediatr 2015;52:
333-334 |
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Childhood Lupus with Microangiopathic
Antiphospholipid Syndrome and Pulmonary Hemorrhage
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Dharmendra Bhadauria, Praveen Etta, Anupma Kaul And *Narayan
Prasad
From Departments of Nephrology and *Renal
Transplantation, SGPGI, Lucknow, Uttar Pradesh, India.
Correspondence to: Dr Dharmendra Bhadauria, Assistant
Professor, Department of Nephrology and Renal Transplantation, Sanjay
Gandhi Post Graduate Institute of Medical Sciences, Lucknow, Uttar
Pradesh, India.
Email: [email protected]
Received: October 24, 2014;
Initial review: December 04, 2014;
Accepted: February 10, 2015.
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Background: Concurrent thrombotic and hemorrhagic manifestations are
uncommon in patients with Antiphospholipid Syndrome. Case
characteristics: A 10-year-old girl with fever, edema, rash and
joint pains, who later developed deep venous thrombosis (DVT), stroke,
thrombotic microangiopathic hemolytic anemia and pulmonary hemorrhage.
Investigations confirmed Antiphospholipid syndrome associated with
systemic lupus erythematosus. Outcome: She went into complete
remission with intravenous immunoglobulins, plasmapheresis,
immunosuppression and anticoagulation. Message: Thrombotic
microangiopathic hemolytic anemia and anti-phospholipid syndrome can be
the presenting manifestations of systemic lupus erythematosus..
Keywords: Anti-phospholipid syndrome, Systemic
lupus erythematosus, Thrombosis.
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A ntiphospholipid syndrome (APS) is an acquired
thrombophilic disorder characterized by presence of antibodies against a
variety of phospholipids (PL) and PL-binding proteins, and uncommonly
presents as Thrombotic microangiopathic hemolytic anemia (TMHA) [1,2].
Less than 1% patients of APS develop multiple organ thromboses and
failure, defined as Catastrophic APS (CAPS) which has a mortality rate
of nearly 50% despite treatment. Here we report a case of Systemic Lupus
Erythematosus (SLE) with APS and TMHA in a child, who subsequently
developed CAPS with multiorgan involvement and pulmonary hemorrhage,
successfully treated with plasma exchange and intravenous
immunoglobulin, (IVIg) along with immunosuppressive drugs and
anticoagulants.
Case Report
A 10-year-old girl presented with three weeks history
of low grade fever, edema, rash over both lower limbs and polyarthralgia.
She had pallor, anasarca, left sided subconjunctival hemorrhage, oral
ulcers, livedo reticularis and purpura over lower limbs, bilateral
pleural effusion, and ascites. Her initial investigations are summarized
in Table I. Urine examination showed proteinuria (3+) with
active urinary sediments. In view of multiorgan involvement, we
suspected underlying connective tissue disorder. Serum Complement levels
were low (C3 and C4 18.7 and 5.8 IU, respectively). Anti-nuclear
antibodies (1:80) and anti double stranded DNA (>200 IU/mL) antibodies
were positive. She was diagnosed as childhood lupus syndrome. Renal
biopsy was not done as parents refused consent. She was given induction
therapy with steroids and parenteral cyclophosphamide.
Table I Laboratory Investigations In Case Presented
Parameter
|
Day-1 of
admission |
Day-6 of
admission |
Hemoglobin (g/dL) |
6.9 |
4.7 |
Total leukocyte count (× 103 / mm3) |
3.0 |
4.0 |
Platelet count (× 103 /mm3) |
72 |
30 |
Corrected reticulocyte count (%) |
2.0 |
5.0 |
Blood urea nitrogen (mg/dL) |
24 |
84 |
Serum creatinine (mg/dL) |
0.96 |
2.6 |
Sodium (mmol/l) |
136 |
133 |
Potassium (mmol/l) |
3.5 |
4.6 |
Corrected calcium (mg/dL) |
8.6 |
8.1 |
Phosphorus (mg/dL) |
4.5 |
5.8 |
Total bilirubin (mg/dL) |
0.3 |
3.0 |
SGPT (IU/L) |
18 |
22 |
Uric acid (mg/dL) |
5.4 |
6.5 |
Lactate dehydrogenase (IU/L) |
450 |
1900 |
Next day, she developed deep vein thrombosis (DVT) of
right lower limb, confirmed by Doppler Anti-cardiolipin antibodies (ACA)
IgG and IgM titers were >300 GPL units/mL and 137 MPL units/mL,
respectively with high Lupus anticoagulant activity (LA) (1:80 titer).
Diagnosis of APS secondary to SLE was made. She was started on heparin,
followed by oral warfarin. Rheumatoid factor and cryoglobulin levels
were negative. She had right sided focal seizure involving face and
upper limb. Magnetic resonance imaging (MRI) of brain showed multiple
acute infarcts in bilateral frontal, parietal and occipital regions. She
also had progressively worsening anemia with reticulocytosis,
thrombocytopenia, azotemia, and elevated lactate dehydrogenase level (Table
I). Peripheral blood smear showed fair number of fragmented red
blood cells, suggestive of associated TMHA. Direct and Indirect Coomb's
tests were negative. Coagulation profile and D-dimer levels were normal.
Subsequently she developed sudden onset
breathlessness, cough, hemoptysis and respiratory failure requiring
mechanical ventilation. Chest radiograph showed bilateral, diffuse
alveolar opacities suggestive of pulmonary hemorrhage. Echocardiography
was normal. She received six sessions of plasmapheresis along with IVIg.
She progressively improved, both clinically and biochemically. Chest
radiograph normalized after three days. After two weeks, her
neurological status was normal, renal functions stabilized, and
thrombocytopenia and microangiopathic hemolytic anemia resolved. Repeat
tests after 12 weeks showed high titers of both ACA and LA. She was
later switched to low dose prednisolone and Mycophenolate mofetil
maintenance therapy, and was continued on oral anticoagulants.
Discussion
Our patient of SLE had concurrent thrombotic and
hemorrhagic manifestations, and was successfully treated with
Immunosuppressive drugs, plasmapheresis and IVIg. About 30% to 40% of
SLE patients have anti-phosphalipid antibodies, but only about 10% have
APS, and less than 1% of APS patients progress to CAPS. Mmanifestations
of APS can range from asymptomatic to life threatening multiorgan
failure. DVT of lower extremities was observed in 29% to 55% of cases of
APS in various studies, and more than half of the patients with
symptomatic DVT had asymptomatic pulmonary embolism. Espinosa, et al.
[3] in their study of 47 episodes of TMHA with APS (in 46 patients),
reported CAPS in 23%. Nesher, et al. [4] reviewed 28 patients
with SLE and TMHA; tests for LA or ACA were positive in 5 out of 8
patients. Prevalence of diffuse alveolar hemorrhage (DAH) in European
patient cohort study of 1000 patients with APS was <1% [2]. Asherson,
et al. [5] reported 6% patients of CAPS with DAH. Elazary, et al.
[6] reported pulmonary hemorrhage in 13 out of 63 patients of APS, and
observed that these patients were more likely to have mitral valve
disease, skin disease, central nervous system (CNS) involvement, and
higher titer of anti-phospholipid antibodies than other APS patients.
Our patient had pulmonary hemorrhage during first attack itself and also
had CNS and skin involvement.
Differential diagnosis of TMHA includes hemolytic
uremic syndrome, thrombotic thrombocytopenic purpura, malignant
hypertension and disseminated intravascular coagulation [3]. Systemic
endothelial cell damage leading to widespread microvascular thrombosis
appears to be a central phenomenon in the pathogenesis of all TMHA
syndromes. Treatment of CAPS associated TMHA includes anticoagulation
therapy, steroids, plasma-pharesis and IVIg [8]. Most patients receive a
combination of these therapies [3]. Rituximab has been tried in few
refractory cases [9].
We conclude that TMHA is a rare complication in
patients with APS, and can be the first clinical manifestation of this
syndrome. Early diagnosis and aggressive institution of treatment is the
key to successful outcome.
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