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P219 Knowledge deficiencies of primary immunodeficiency diseases among internal medicine residents
Abstracts: Poster Sessions / Ann Allergy Asthma Immunol 117 (2016) S22eS124
Methods: A 9 day old female born full term to Mennonite parents presented to the hospital for evaluation due to an abnormal T-cell Receptor Excision Circle (TREC) value of 0.35 copies/uL (state cutoff > 29 copies/uL) on newborn screen. Upon presentation, the patient appeared well and had no abnormal findings on physical exam. She was feeding normally and had no symptoms of infection. B-cell and T-cell subset analysis revealed absent T and B-cells but a normal number of Natural Killer (NK) cells. She was subsequently diagnosed with T-B-NK+ SCID. Genetic testing was done to identify common mutations seen in the Amish community associated with SCID. A homozygous mutation in the ADA gene on human chromosome 20q12-q13.11 was found establishing a diagnosis of Adenosine deaminase (ADA) deficiency. Results: The patient is currently receiving Adagen therapy as a bridge to her final treatment, either stem cell transplant or gene therapy. Additionally, she is receiving anti-infective prophylaxis with Bactrim, fluconazole, and azithromycin, along with monthly intravenous immunoglobulin infusions. Conclusion: Newborn screening TREC analysis was initiated in Tennessee in January 2016 in order to screen newborns for T cell related immunodeficiencies. This is the first known diagnosis of SCID identified by newborn screening in Tennessee. Due to early diagnosis, she is able to receive early and appropriate therapy to prevent infection while she awaits definitive therapy.
P219 KNOWLEDGE DEFICIENCIES OF PRIMARY IMMUNODEFICIENCY DISEASES AMONG INTERNAL MEDICINE RESIDENTS S. Alvarado, K. Mattaparthi, J. Purser, Tulsa, OK. Introduction: Primary immunodeficiency diseases (PID) receive minimal instructional time during medical training. Appropriate referrals for testing require that primary care providers and hospitalists have some knowledge of PID. We aimed to increase the knowledge of PID in an internal medicine residency program. Methods: We developed a multiple-choice test about PID primarily using board review question banks. We administered the test to a group of medical and physician assistant students, interns, and second- and third- year residents in our internal medicine residency program. This was followed by a 25-minute teaching presentation on PID and then the post-test. Results: 35 learners ranging from medical or physician assistant students to third-year residents participated. The average exam score on the pre-test was 49.7%. There was no difference in these scores based on level of training (p ¼ .958). The average post-test score was 76.3%. The difference between pre- and post-test scores was statistically significant (p < .001). Partial eta squared indicated approximately 50.6% of the variance in PID exam scores could be attributed to the teaching presentation intervention. Pre- and posttest scores were significantly increased in the topic areas of common variable immunodeficiency (p ¼ .004), complement deficiency (p < .001), and complications of immunoglobulin replacement (p < .001). Conclusion: We found that baseline knowledge of PID was lacking in our internal medicine residency, and that knowledge among senior level residents was no greater than among medical students. A short presentation was able to significantly increase the knowledge of PID among all learners.
P220 SEVERE HYPOGAMMAGLOBULINEMIA AND POOR ANTIBODY RESPONSE IN AN ASYMPTOMATIC PATIENT WITH HETEROZYGOUS TACI MUTATION B. Cohen*, R. Mehta, L. Rampur, A. Rubinstein, Bronx, NY. Introduction: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced serum
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immunoglobulin levels and increased risk of infections, autoimmunity, and cancer. Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) mutations are found in 8-10% of CVID cases and sometimes in healthy non-hypogammaglobulinemic subjects. We present a 6 year-old boy with a heterozygous TACI mutation who had significant hypogammaglobulinemia and poor antibody responses but no infectious or autoimmune history. Methods: Case description Results: A 6 year-old boy with no family history of immunodeficiency presented with a diffuse rash from Gianotti-Crosti syndrome. After rash resolution, he developed fingernail shedding and cognitive slowing with prolonged recovery. Immune work-up revealed significant hypogammaglobulinemia [IgG 84mg/dL (633-1280), IgA <5mg/dL (48-207), IgM 27mg/dL (33-207), and low IgG subclasses]. He had no history of recurrent or serious infections, autoimmunity, or gastrointestinal or renal protein loss. Further work-up revealed no protective antibodies to Streptococcus pneumoniae, measles, mumps, and tetanus antigens despite being fully vaccinated and no history of vaccine-associated infections. He developed adequate S. pneumoniae response after re-vaccination. B cell count was normal but with low switched memory B cells, and genetic testing revealed a heterozygous TACI mutation of unknown significance (c.310T>C) and a homozygous synonymous TACI mutation. Conclusion: Although up to 10% of patients with CVID exhibit homozygous or heterozygous TACI mutations, heterozygous carriers can have normal gammaglobulin levels and no associated infectious history. We report a heterozygous TACI mutation of unknown significance in a patient with severe hypogammaglobulinemia and poor antibody responses without history of infections or autoimmunity.
P221 IMMUNOGLOBULIN G4-RELATED DISEASE (IGG4-RD) PRESENTING AS MULTIPLE MYELOMA S. Alandijani*, A. Bulkhi, R. Lockey, D. Ledford, Tampa, FL. Introduction: IgG4-RD is a rare syndrome with various presentations including angioedema, eosinophilia, elevated serum IgG4 and lymphadenopathy. Methods: A 71-year-old female with a history of Sjogren’s syndrome presents with fatigue, lethargy and back pain. Examination reveals diffuse lymphadenopathy. A left axillary lymph node biopsy shows clonal plasma cells with kappa light chains. The bone marrow biopsy shows normocellular marrow for the age with maturing trilineage hematopoiesis and kappa restricted plasma cell neoplasm. She is started on bortezomib (proteasome inhibitor), cyclophosphamide and dexamethasone for 6 weeks for a presumed multiple myeloma. A subsequent review of her bone marrow and lymph node biopsies reveals few plasma cells and many CD138+ immunoblasts and 50% IgG4 cells, consistent with IgG4-RD. Cytotoxic therapy is discontinued and she is started on tapering doses of prednisone. Her latest serum IgG4 is 276 mg/dl (2.4-121.0 mg/dl). Results: The etiology of IgG4-RD is unknown and requires a tissue biopsy typically showing extensive lymphocyte and plasma cells infiltration, IgG4 immunoblasts, storiform fibrosis (fibrosis in a cartwheel distribution), eosinophil tissue infiltration and obliterative phlebitis. Elevated serum IgG4 levels or eosinophilia may be present. Treatment with systemic glucocorticosteroids is recommended in symptomatic and asymptomatic cases involving kidney or pancreas. Conclusion: IgG4-RD is an immune-mediated condition that may affect multiple organs. Allergists/Immunologists should include IgG4-RD in differential diagnosis of subjects with
Methods: A 9 day old female born full term to Mennonite parents presented to the hospital for evaluation due to an abnormal T-cell Receptor Excision Circle (TREC) value of 0.35 copies/uL (state cutoff > 29 copies/uL) on newborn screen. Upon presentation, the patient appeared well and had no abnormal findings on physical exam. She was feeding normally and had no symptoms of infection. B-cell and T-cell subset analysis revealed absent T and B-cells but a normal number of Natural Killer (NK) cells. She was subsequently diagnosed with T-B-NK+ SCID. Genetic testing was done to identify common mutations seen in the Amish community associated with SCID. A homozygous mutation in the ADA gene on human chromosome 20q12-q13.11 was found establishing a diagnosis of Adenosine deaminase (ADA) deficiency. Results: The patient is currently receiving Adagen therapy as a bridge to her final treatment, either stem cell transplant or gene therapy. Additionally, she is receiving anti-infective prophylaxis with Bactrim, fluconazole, and azithromycin, along with monthly intravenous immunoglobulin infusions. Conclusion: Newborn screening TREC analysis was initiated in Tennessee in January 2016 in order to screen newborns for T cell related immunodeficiencies. This is the first known diagnosis of SCID identified by newborn screening in Tennessee. Due to early diagnosis, she is able to receive early and appropriate therapy to prevent infection while she awaits definitive therapy.
P219 KNOWLEDGE DEFICIENCIES OF PRIMARY IMMUNODEFICIENCY DISEASES AMONG INTERNAL MEDICINE RESIDENTS S. Alvarado, K. Mattaparthi, J. Purser, Tulsa, OK. Introduction: Primary immunodeficiency diseases (PID) receive minimal instructional time during medical training. Appropriate referrals for testing require that primary care providers and hospitalists have some knowledge of PID. We aimed to increase the knowledge of PID in an internal medicine residency program. Methods: We developed a multiple-choice test about PID primarily using board review question banks. We administered the test to a group of medical and physician assistant students, interns, and second- and third- year residents in our internal medicine residency program. This was followed by a 25-minute teaching presentation on PID and then the post-test. Results: 35 learners ranging from medical or physician assistant students to third-year residents participated. The average exam score on the pre-test was 49.7%. There was no difference in these scores based on level of training (p ¼ .958). The average post-test score was 76.3%. The difference between pre- and post-test scores was statistically significant (p < .001). Partial eta squared indicated approximately 50.6% of the variance in PID exam scores could be attributed to the teaching presentation intervention. Pre- and posttest scores were significantly increased in the topic areas of common variable immunodeficiency (p ¼ .004), complement deficiency (p < .001), and complications of immunoglobulin replacement (p < .001). Conclusion: We found that baseline knowledge of PID was lacking in our internal medicine residency, and that knowledge among senior level residents was no greater than among medical students. A short presentation was able to significantly increase the knowledge of PID among all learners.
P220 SEVERE HYPOGAMMAGLOBULINEMIA AND POOR ANTIBODY RESPONSE IN AN ASYMPTOMATIC PATIENT WITH HETEROZYGOUS TACI MUTATION B. Cohen*, R. Mehta, L. Rampur, A. Rubinstein, Bronx, NY. Introduction: Common variable immunodeficiency (CVID) is a primary immunodeficiency characterized by reduced serum
S87
immunoglobulin levels and increased risk of infections, autoimmunity, and cancer. Transmembrane activator and calcium-modulating cyclophilin ligand interactor (TACI) mutations are found in 8-10% of CVID cases and sometimes in healthy non-hypogammaglobulinemic subjects. We present a 6 year-old boy with a heterozygous TACI mutation who had significant hypogammaglobulinemia and poor antibody responses but no infectious or autoimmune history. Methods: Case description Results: A 6 year-old boy with no family history of immunodeficiency presented with a diffuse rash from Gianotti-Crosti syndrome. After rash resolution, he developed fingernail shedding and cognitive slowing with prolonged recovery. Immune work-up revealed significant hypogammaglobulinemia [IgG 84mg/dL (633-1280), IgA <5mg/dL (48-207), IgM 27mg/dL (33-207), and low IgG subclasses]. He had no history of recurrent or serious infections, autoimmunity, or gastrointestinal or renal protein loss. Further work-up revealed no protective antibodies to Streptococcus pneumoniae, measles, mumps, and tetanus antigens despite being fully vaccinated and no history of vaccine-associated infections. He developed adequate S. pneumoniae response after re-vaccination. B cell count was normal but with low switched memory B cells, and genetic testing revealed a heterozygous TACI mutation of unknown significance (c.310T>C) and a homozygous synonymous TACI mutation. Conclusion: Although up to 10% of patients with CVID exhibit homozygous or heterozygous TACI mutations, heterozygous carriers can have normal gammaglobulin levels and no associated infectious history. We report a heterozygous TACI mutation of unknown significance in a patient with severe hypogammaglobulinemia and poor antibody responses without history of infections or autoimmunity.
P221 IMMUNOGLOBULIN G4-RELATED DISEASE (IGG4-RD) PRESENTING AS MULTIPLE MYELOMA S. Alandijani*, A. Bulkhi, R. Lockey, D. Ledford, Tampa, FL. Introduction: IgG4-RD is a rare syndrome with various presentations including angioedema, eosinophilia, elevated serum IgG4 and lymphadenopathy. Methods: A 71-year-old female with a history of Sjogren’s syndrome presents with fatigue, lethargy and back pain. Examination reveals diffuse lymphadenopathy. A left axillary lymph node biopsy shows clonal plasma cells with kappa light chains. The bone marrow biopsy shows normocellular marrow for the age with maturing trilineage hematopoiesis and kappa restricted plasma cell neoplasm. She is started on bortezomib (proteasome inhibitor), cyclophosphamide and dexamethasone for 6 weeks for a presumed multiple myeloma. A subsequent review of her bone marrow and lymph node biopsies reveals few plasma cells and many CD138+ immunoblasts and 50% IgG4 cells, consistent with IgG4-RD. Cytotoxic therapy is discontinued and she is started on tapering doses of prednisone. Her latest serum IgG4 is 276 mg/dl (2.4-121.0 mg/dl). Results: The etiology of IgG4-RD is unknown and requires a tissue biopsy typically showing extensive lymphocyte and plasma cells infiltration, IgG4 immunoblasts, storiform fibrosis (fibrosis in a cartwheel distribution), eosinophil tissue infiltration and obliterative phlebitis. Elevated serum IgG4 levels or eosinophilia may be present. Treatment with systemic glucocorticosteroids is recommended in symptomatic and asymptomatic cases involving kidney or pancreas. Conclusion: IgG4-RD is an immune-mediated condition that may affect multiple organs. Allergists/Immunologists should include IgG4-RD in differential diagnosis of subjects with