Neutropenia, With a Cyclical Pattern, In Antibody Deficiency

Abstract

RATIONALE: We report 2 patients presenting with cyclic neutropenia, who were found to have antibody deficiency, with no ELA-2 mutations.RESULTS/CASES: Patient A is a 31 yo white female with a history of recurrent aphthous ulcers, skin infections, and pharyngitis, found to have a neutrophil count of 90 during her third pregnancy. Upon delivery, the infant had severe neutropenia requiring G-CSF and WBC infusions, but had a spontaneous resolution at around six months of age. Evaluation of the mother revealed a cyclical neutropenia pattern, with an 18-24 day cycle and a nadir count of 270. She had a poor antibody response to pneumococcal vaccine. G-CSF treatment successfully increased her neutrophils, but was discontinued because of severe side effects. She then developed recurrent aphthous ulcers, folliculitis, and three UTIs. She was started on IVIG (600mg/kg) with significant improvement of her symptoms, and a “re-setting” of her neutrophil nadir to about 600.Patient B is a 49 yo white female with recurrent sinusitis, sore throat, and aphthous ulcers, found to have cyclical neutropenia with a 6-week cycle and a nadir of 234. She was found to have antibody deficiency with no response to Pneumococcus, Tetanus or Diphtheria. She did well on prophylactic antibiotics.Both patients did not have ELA-2 mutations.CONCLUSIONS: Cyclic neutropenia can have several causes. These two patients suggest that neutropenia associated with anti-neutrophil antibody and/or antibody deficiency may have a cyclical pattern. Most importantly, patient A, who had anti-neutrophil antibodies, suggests that IVIG for such patients can result in significant clinical improvement. RATIONALE: We report 2 patients presenting with cyclic neutropenia, who were found to have antibody deficiency, with no ELA-2 mutations. RESULTS/CASES: Patient A is a 31 yo white female with a history of recurrent aphthous ulcers, skin infections, and pharyngitis, found to have a neutrophil count of 90 during her third pregnancy. Upon delivery, the infant had severe neutropenia requiring G-CSF and WBC infusions, but had a spontaneous resolution at around six months of age. Evaluation of the mother revealed a cyclical neutropenia pattern, with an 18-24 day cycle and a nadir count of 270. She had a poor antibody response to pneumococcal vaccine. G-CSF treatment successfully increased her neutrophils, but was discontinued because of severe side effects. She then developed recurrent aphthous ulcers, folliculitis, and three UTIs. She was started on IVIG (600mg/kg) with significant improvement of her symptoms, and a “re-setting” of her neutrophil nadir to about 600. Patient B is a 49 yo white female with recurrent sinusitis, sore throat, and aphthous ulcers, found to have cyclical neutropenia with a 6-week cycle and a nadir of 234. She was found to have antibody deficiency with no response to Pneumococcus, Tetanus or Diphtheria. She did well on prophylactic antibiotics. Both patients did not have ELA-2 mutations. CONCLUSIONS: Cyclic neutropenia can have several causes. These two patients suggest that neutropenia associated with anti-neutrophil antibody and/or antibody deficiency may have a cyclical pattern. Most importantly, patient A, who had anti-neutrophil antibodies, suggests that IVIG for such patients can result in significant clinical improvement.