1. Clinical course after Rituximab
RITUXIMAB IN THE MANAGEMENT OF ANTIPHOSPHOLIPID ANTIBODIES ASSOCIATED CHOREA IN A CHILD WITH LUPUS
Vignesh P, Sikha Agarwal, Anju Gupta, Jasmina Ahluwalia#, Deepti Suri, Amit Rawat, Surjit Singh
Pediatric Allergy and Immunology Unit, Department of Pediatrics, Advanced Pediatrics Centre, PGIMER, Chandigarh, India
#Department of Hematopathology, PGIMER, Chandigarh, India
Introduction
Clinical course after Rituximab
Variable prevalence of neuropsychiatric manifestations in children with lupus, reported to be between 20%-95%1
Chorea as an isolated manifestation in lupus children is rare
Result of both thrombotic and nonthrombotic immune mediated damage2
Strongly linked to coexisting antiphospholipid antibodies (APLA) (4%)
Showed complete symptom recovery after rituximab infusions. APLA was negative six months down the line
Done well for next one year but later succumbed to pneumonia and acute respiratory distress syndrome
MRI Brain
Clinical Profile
YEAR year girl diagnosed to have lupus3
Presented with spastic quadriparesis, constitutional symptoms, malar rash, anemia thrombocytopenia, ANA 4+ diffuse pattern, raised anti- ds DNA titres.
APLA- Lupus anticoagulant (LA) positive. IgM anti cardiolipin (aCL) antibodies elevated. T2 MRI brain and spine images- multiple increased signal intensity changes, [Fig. 1A].
Started on oral prednisolone, hydroxychloroquine, aspirin.
Later Prednisolone tapered, started on azathioprine maintenance.
Remarkable improvement in two months.
YEAR Relapsed with multiple joint pains, seizures and foot drop related to mononeuritis multiplex.
MRI brain- T2 FLAIR periventricular hyperintensities, [Fig. 1B].
Improved with oral prednisolone 2 mg/kg. Azathioprine restarted.
YEAR Relapsed with seizures and chorea. MRI- T2 white matter hyperintensities and no evidence of thrombus.
LA positive. Responded to IV methylprednisolone and cyclophosphamide pulses.
YEAR LA negative, aCL- negative, anti-beta2 glycoprotein I antibody (beta2GPI)- negative.
YEAR LA negative, aCL- negative, anti-beta2GPI- negative.
YEAR Relapsed with choreiform movements and aggressive behavior. LA positive. MRI brain- normal.
No response to haloperidol, steroids and warfarin.
Administered 3 doses of rituximab (500 mg/m2 at one weekly interval). B A
Figure 1. MRI Brain showing A) T2 weighted hyperintensities in corona radiata and centrum semiovale. B) T2 FLAIR hyperintensities in periventricular white matter
Discussion
High dose steroids and cyclophosphamide consitute the initial primary treatment of neuropsychiatric lupus
Rituximab has been used successfully in management of nephritis and hematological manifestations of lupus
Few case reports suggest some efficacy of rituximab in neuropsychiatric manifestations4
Moreover, early remission following rituximab in the index patient suggests its promising role in neuropsychiatric lupus
Conclusion
Rituximab can be considered as an effective treatment modality in APLA related chorea where conventional measures have failed
References
1. Singh S, Gupta M, Ahluwalia J, et al. Neuropsychiatric manifestations and antiphospholipid antibodies in pediatric onset lupus: 14 years of experience from a tertiary center of North India. Rheumatol Int 2009; 29: 1455–1461.
2. Avcin T, Silverman ED. Antiphospholipid antibodies in pediatric systemic lupus erythematosus and the antiphospholipid syndrome. Lupus 2007; 16: 627–633.
3. Gupta A, Singh S, Singh P, et al. Spastic quadriparesis: an unusual early manifestation of systemic lupus erythematosus. Scand J Rheumatol 2003; 32: 189–190.
4. Brogna C, Mariotti P, Manna R. Conventional and intravenous immunoglobulin therapy in paediatric antiphospholipid antibodies-related chorea. Lupus 2014; 23: 1449–1451.