In the January 2009 edition of Pediatrics, Kumar et al1 describe the
safety and efficacy of rituximab for the treatment of autoimmune
thrombocytopenia and autoimmune hemolytic anemia (AIHA) in pediatric
systemic lupus erythematosus (SLE). Despite the fact that all patients
experienced “complete B cell depletion” for four to seven months, the
authors reported no serious infections and suggest that routine
intravenous gamma globulin (IVIg) may not be required for these patients.
We would like to report a child who suffered from recurrent serious
infections for five months after receipt of a single dose of rituximab.
The patient was a 20 month-old female with AIHA who received one dose
of rituximab (375 mg/m2) at seventeen months of age when her hemoglobin
decreased to 5.4 g/dL despite oral corticosteroid therapy. Although her
anemia resolved 2 weeks later, she subsequently required 6 separate
hospital admissions for pneumonia, sinusitis, and periorbital cellulitis.
An immune evaluation demonstrated lymphopenia (absolute lymphocyte count
of 960 cells/mm3), complete B lymphocyte depletion (CD19+ cells of 0
cells/mm3), and hypogammaglobulinemia (IgG of 117 mg/dL). She was started
on monthly IVIg (400 mg/kg) and her corticosteroid dose was tapered. Her
B-lymphocyte count normalized seven months after rituximab was given, at
which time her anemia recurred. Corticosteroid therapy was re-started with
successful recovery of her hemoglobin concentration. She continues to
receive replacement immunoglobulin therapy and remains healthy.
Rituximab administration results in rapid and often prolonged
depletion of CD20+ B cells2,3,4. While the use of rituximab for various
hematological disorders shows promise, the risk of potential long-term
immunosuppression must be considered, especially in the context of
concomitant prolonged corticosteroid therapy or use of other
immunosuppressive agents.
We suggest a routine baseline screen of humoral immunity with
quantitative analysis of serum IgG, IgA, IgM and B-lymphocyte numbers
identified by CD19 and/or CD20 prior to rituximab administration in
children. Following rituximab administration, IgG levels and B-lymphocyte
numbers should be monitored over time, especially in those patients
developing recurrent infections, failure to thrive, or other clinical
manifestations of secondary, iatrogenic immunodeficiency. Such measures
may identify patients with underlying humoral immunodeficiency in whom
rituximab therapy may be contraindicated, and also identify candidates for
IVIg replacement therapy.
REFERENCES
1. S Kumar, S Benseler, Melanie Kirby-Allen, and Earl D. Silverman. B-Cell
Depletion for Autoimmune Thrombocytopenia and Autoimmune Hemolytic Anemia
in Pediatric Systemic Lupus Erythematosus. Pediatrics 2009; 123: e159-
e163.
2. A Rao, M Kelly, M Musselman, J Ramada et al. Safety, Efficacy, and
Immune Reconstitution After Rituximab Therapy in Pediatric Patients with
Chronic or Refractory Hematologic Autoimmune Cytopenias. Pediatr Blood
Cancer 2008; 50: 822–825.
3. M El-Hallak, B Binstadt, A Leichtner et al. Clinical Effects and Safety
of Rituximab for Treatment of Refractory Pediatric Autoimmune Diseases. J
Pediatr 2007;150: 376-82.
4. P Quartier, B Brethon, P Philippet et al. Treatment of childhood
autoimmune haemolytic anaemia with rituximab. The Lancet 2001; 358: 1511-
1513.
Conflict of Interest:
None declared
eLetters: ![[Read eLetters]](/icons/misc/sectionDOWN.gif){kind=icon}
