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P228 Diagnosing and treating enteroviral CNS infections in agammaglobulinemia
S90
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
Methods: This is an IRB-approved, retrospective study involving 22 patients (average age 62.2 years) with suspected SAD who received PNCV followed by PCV at intervals between 1-36 months. Inferior responders were defined as mounting less than 70% protective pneumococcal titers (1.3mcg/mL with at least a 2-4 fold increase). Results: A non-protective response to PCV was found in 72.7% (16/22) of patients. Of those who received PCV less than 12 months after PNCV, 45% (10/22) were non responders and 50% (3/6) were responders. Conclusion: The majority of the patients with inferior response to PNCV also had an inferior response to PCV. Administration of PCV less than a year after PNCV did not lead to a decrease response compared to those who received PCV after 12 months. The data demonstrates patients with suspected SAD may not benefit from a conjugated vaccine, suggesting a defect that may affect more than just humoral responses.
P228 DIAGNOSING AND TREATING ENTEROVIRAL CNS INFECTIONS IN AGAMMAGLOBULINEMIA J. Lee*1, G. Seminario2, S. Jyonouchi1, I. Moreira2, A. Gomez Raccio2, L. Bezrodnik2, K. Sullivan1, 1. Philadelphia, PA; 2. Buenos Aires, Argentina. Introduction: Patients with agammaglobulinemia can develop severe, life-threatening enteroviral CNS infections, even on adequate immunoglobulin replacement. This knowledge is critical to guide diagnosis and offer treatment. We aim to report our experience diagnosing and treating enteroviral CNS infections in a cohort of agammaglobulinemia patients. Methods: We reviewed charts of 4 agammaglobulinemia patients with enteroviral CNS infection. Results: Ages ranged from 6 months to 5 years at onset of CNS symptoms. Three patients had known agammaglobulinemia (2 Xlinked, 1 autosomal recessive) and were on therapeutic IVIG. One was diagnosed with XLA subsequently. Three patients presented with recurrent meningoencephalitis, one with progressive developmental regression. All patients underwent lumbar puncture at least twice; CSF enterovirus PCR returned negative each time. Positive enterovirus PCR ultimately resulted from a third CSF sample in one patient, stool samples in two, and on brain biopsy in the patient with developmental regression. Two patients have had resolution of symptoms; one with high dose IVIG and one with high dose IVIG, intrathecal IG, and pocapavir combined. The other two patients remain on high dose IVIG. Discussion: Neurodevelopmental symptoms in agammaglobulinemia are highly suspicious for enteroviral infection. Multiple repeat CSF studies, or additional studies such as brain biopsy or stool samples, may be necessary to yield the diagnosis. Treatment options are currently limited but include high dose IVIG. Anti-enteroviral agents such as pocapavir and pleconaril have been offered for compassionate use in the past and were effective but are not available currently. Fluoxetine and itraconazole have shown antienteroviral properties in-vitro and may warrant clinical studies.
P229 DELAYED DIAGNOSIS OF B-CELL LYMPHOMA IN A PATIENT WITH HYPER-IGE SYNDROME: CASE REPORT T. Weinberger*, C. Cunningham-Rundles, T. Smith, J. Truglio, New York, NY. Introduction: Patient’s with Hyper-IgE syndrome have an increased relative risk of lymphoma, with the most common being Diffuse Large B-Cell Lymphoma (DLBCL). However, cancerous growths may be mistaken for an infectious process in these patients and diagnosis can be delayed. Case: Patient is a 26-year-old male diagnosed with Hyper-IgE syndrome in infancy after suffering from recurrent staphylococcal infections and severe eczema. His IgE levels in 2009 were 6,730 KU/L. In
2013 the patient presented with a non-painful and non-erythematous submental growth. He also had regional lymphadenopathy, consistent with recurrent facial and dental abscesses. Labs were notable for an LDH of 369. CT scan of the growth showed a homogeneous welldelineated node. Fine needle aspiration of the mass showed a granuloma with a mixed lymphocytic population. The mass partially regressed after completing a course of antibiotics and was thought to have been a reactive lymph node. Patient was lost to follow up and represented in 2016 with multiple abscesses and an enlargement of the submental growth while off antibiotic prophylaxis. After two weeks of appropriate antibiotic therapy his acute infection resolved but the submental growth was persistently larger in size, measuring approximately 3.5x2cm. A submental lymph node excision was completed and pathology showed DLBCL, non-germinal center type. Immunophenotype showed a high growth fraction (CD10-, MUM1+, BCL-6+; Ki-67 90%), associated with a poor prognosis. Conclusion: This case presentation highlights that, in addition to abscesses and lymphadenitis, B-cell lymphomas have been reported in patients with Hyper IgE syndrome and this should be on the differential.
P230 SPECIFIC ANTIBODY DEFICIENCY IN CHILDREN WITH DOWN SYNDROME AND LIFE-THREATENING INFECTIONS W. De Jesus-Rojas*, K. McBeth, K. Smith, S. Pacheco, Houston, TX. Introduction: Specific antibody deficiency (SAD) is characterized by recurrent sinopulmonary infections in children and adults. Patients with Down syndrome have recurrent infections and immunological abnormalities including T and B cell lymphopenia with impaired lymphoproliferative and antibody vaccine response. However, a specific immunological diagnosis has not been identified. Methods: The immunological characterization of three fully immunized patients (2-4 years) with Down syndrome and lifethreatening infections (i.e. streptococcal, staphylococcal bacteremia and complicated pneumonia with empyema) was obtained. Immunoglobulin classes, specific antibody response to vaccines, lymphocyte phenotyping/function and B-cell subsets, were analyzed. Patients with poor response to streptococcal polysaccharide antigens were immunized with the 23-valent-pneumococcal vaccine. Results: The immune evaluation was significant for normal lymphocyte phenotyping, lymphoproliferative assay, immunoglobulin classes and antibody responses to diphtheria and tetanus. Total memory B-cell including class switched (CD19+, CD27+, IgD-) and non-switched cells (CD19+, CD27+, IgD+) were abnormal in one patient. Pre-immunization titers to streptococcal antigens were decreased below protective levels (1.3 mg/mL) in all patients (5/23, 0/13, 0/13). There was a limited increase in the antibody response after 6 weeks post 23-valent-pneumococcal immunization (8/23, 14/23, 11/23), respectively. Conclusion: Patients with Down syndrome and life-threatening infections have poor vaccine response to polysaccharide antigens and may have decreased percentages of switched memory B-cells. These findings are consistent with SAD phenotypes. SAD must be considered in the differential diagnosis of patients with Down syndrome and recurrent infections.
P231 SERUM CYTIDINE DEAMINASE ACTIVITY IN PATIENTS WITH VIRAL INFECTIONS K. Pavlov1, L. Titov*1, L. DuBuske2, 1. Minsk, Belarus; 2. Gardner, MA. Background: Cytidine deaminase (CDA) completes the somatic recombination and somatic hypermutation processes for immunoglobulin heavy chains genes. CDA activity is present in normal serum and increases during eclampsia, pre-eclampsia and breast cancer and changes in HIV and HCV patients. Methods: CDA activity(IU / L) was measured in serum samples of patients witch were examined for HIV (n¼77), HCV (n¼29),
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
Methods: This is an IRB-approved, retrospective study involving 22 patients (average age 62.2 years) with suspected SAD who received PNCV followed by PCV at intervals between 1-36 months. Inferior responders were defined as mounting less than 70% protective pneumococcal titers (1.3mcg/mL with at least a 2-4 fold increase). Results: A non-protective response to PCV was found in 72.7% (16/22) of patients. Of those who received PCV less than 12 months after PNCV, 45% (10/22) were non responders and 50% (3/6) were responders. Conclusion: The majority of the patients with inferior response to PNCV also had an inferior response to PCV. Administration of PCV less than a year after PNCV did not lead to a decrease response compared to those who received PCV after 12 months. The data demonstrates patients with suspected SAD may not benefit from a conjugated vaccine, suggesting a defect that may affect more than just humoral responses.
P228 DIAGNOSING AND TREATING ENTEROVIRAL CNS INFECTIONS IN AGAMMAGLOBULINEMIA J. Lee*1, G. Seminario2, S. Jyonouchi1, I. Moreira2, A. Gomez Raccio2, L. Bezrodnik2, K. Sullivan1, 1. Philadelphia, PA; 2. Buenos Aires, Argentina. Introduction: Patients with agammaglobulinemia can develop severe, life-threatening enteroviral CNS infections, even on adequate immunoglobulin replacement. This knowledge is critical to guide diagnosis and offer treatment. We aim to report our experience diagnosing and treating enteroviral CNS infections in a cohort of agammaglobulinemia patients. Methods: We reviewed charts of 4 agammaglobulinemia patients with enteroviral CNS infection. Results: Ages ranged from 6 months to 5 years at onset of CNS symptoms. Three patients had known agammaglobulinemia (2 Xlinked, 1 autosomal recessive) and were on therapeutic IVIG. One was diagnosed with XLA subsequently. Three patients presented with recurrent meningoencephalitis, one with progressive developmental regression. All patients underwent lumbar puncture at least twice; CSF enterovirus PCR returned negative each time. Positive enterovirus PCR ultimately resulted from a third CSF sample in one patient, stool samples in two, and on brain biopsy in the patient with developmental regression. Two patients have had resolution of symptoms; one with high dose IVIG and one with high dose IVIG, intrathecal IG, and pocapavir combined. The other two patients remain on high dose IVIG. Discussion: Neurodevelopmental symptoms in agammaglobulinemia are highly suspicious for enteroviral infection. Multiple repeat CSF studies, or additional studies such as brain biopsy or stool samples, may be necessary to yield the diagnosis. Treatment options are currently limited but include high dose IVIG. Anti-enteroviral agents such as pocapavir and pleconaril have been offered for compassionate use in the past and were effective but are not available currently. Fluoxetine and itraconazole have shown antienteroviral properties in-vitro and may warrant clinical studies.
P229 DELAYED DIAGNOSIS OF B-CELL LYMPHOMA IN A PATIENT WITH HYPER-IGE SYNDROME: CASE REPORT T. Weinberger*, C. Cunningham-Rundles, T. Smith, J. Truglio, New York, NY. Introduction: Patient’s with Hyper-IgE syndrome have an increased relative risk of lymphoma, with the most common being Diffuse Large B-Cell Lymphoma (DLBCL). However, cancerous growths may be mistaken for an infectious process in these patients and diagnosis can be delayed. Case: Patient is a 26-year-old male diagnosed with Hyper-IgE syndrome in infancy after suffering from recurrent staphylococcal infections and severe eczema. His IgE levels in 2009 were 6,730 KU/L. In
2013 the patient presented with a non-painful and non-erythematous submental growth. He also had regional lymphadenopathy, consistent with recurrent facial and dental abscesses. Labs were notable for an LDH of 369. CT scan of the growth showed a homogeneous welldelineated node. Fine needle aspiration of the mass showed a granuloma with a mixed lymphocytic population. The mass partially regressed after completing a course of antibiotics and was thought to have been a reactive lymph node. Patient was lost to follow up and represented in 2016 with multiple abscesses and an enlargement of the submental growth while off antibiotic prophylaxis. After two weeks of appropriate antibiotic therapy his acute infection resolved but the submental growth was persistently larger in size, measuring approximately 3.5x2cm. A submental lymph node excision was completed and pathology showed DLBCL, non-germinal center type. Immunophenotype showed a high growth fraction (CD10-, MUM1+, BCL-6+; Ki-67 90%), associated with a poor prognosis. Conclusion: This case presentation highlights that, in addition to abscesses and lymphadenitis, B-cell lymphomas have been reported in patients with Hyper IgE syndrome and this should be on the differential.
P230 SPECIFIC ANTIBODY DEFICIENCY IN CHILDREN WITH DOWN SYNDROME AND LIFE-THREATENING INFECTIONS W. De Jesus-Rojas*, K. McBeth, K. Smith, S. Pacheco, Houston, TX. Introduction: Specific antibody deficiency (SAD) is characterized by recurrent sinopulmonary infections in children and adults. Patients with Down syndrome have recurrent infections and immunological abnormalities including T and B cell lymphopenia with impaired lymphoproliferative and antibody vaccine response. However, a specific immunological diagnosis has not been identified. Methods: The immunological characterization of three fully immunized patients (2-4 years) with Down syndrome and lifethreatening infections (i.e. streptococcal, staphylococcal bacteremia and complicated pneumonia with empyema) was obtained. Immunoglobulin classes, specific antibody response to vaccines, lymphocyte phenotyping/function and B-cell subsets, were analyzed. Patients with poor response to streptococcal polysaccharide antigens were immunized with the 23-valent-pneumococcal vaccine. Results: The immune evaluation was significant for normal lymphocyte phenotyping, lymphoproliferative assay, immunoglobulin classes and antibody responses to diphtheria and tetanus. Total memory B-cell including class switched (CD19+, CD27+, IgD-) and non-switched cells (CD19+, CD27+, IgD+) were abnormal in one patient. Pre-immunization titers to streptococcal antigens were decreased below protective levels (1.3 mg/mL) in all patients (5/23, 0/13, 0/13). There was a limited increase in the antibody response after 6 weeks post 23-valent-pneumococcal immunization (8/23, 14/23, 11/23), respectively. Conclusion: Patients with Down syndrome and life-threatening infections have poor vaccine response to polysaccharide antigens and may have decreased percentages of switched memory B-cells. These findings are consistent with SAD phenotypes. SAD must be considered in the differential diagnosis of patients with Down syndrome and recurrent infections.
P231 SERUM CYTIDINE DEAMINASE ACTIVITY IN PATIENTS WITH VIRAL INFECTIONS K. Pavlov1, L. Titov*1, L. DuBuske2, 1. Minsk, Belarus; 2. Gardner, MA. Background: Cytidine deaminase (CDA) completes the somatic recombination and somatic hypermutation processes for immunoglobulin heavy chains genes. CDA activity is present in normal serum and increases during eclampsia, pre-eclampsia and breast cancer and changes in HIV and HCV patients. Methods: CDA activity(IU / L) was measured in serum samples of patients witch were examined for HIV (n¼77), HCV (n¼29),