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The Success of Newborn Screening for Severe Combined Immunodeficiency, Our Hospital's Experience
34
Good's Syndrome Presenting As T-Cell Large Granular Lymphocyte Leukemia Caroline V. Caperton, MD, MSPH, Sudhir Gupta, MD, PhD, FAAAAI; Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California School of Medicine, Irvine, CA. RATIONALE: Good Syndrome is an adult-onset immunodeficiency defined by hypogammaglobulinemia, low number of B cells, and benign thymic tumor. Rarely associated with malignancies. We report a case of Good’s syndrome that presented as T-cell Large granular lymphocytic leukemia (LGL). METHODS: Lymphocyte subset by flow cytometry, response to recall antigens and mitogens by 3H thymidine incorporation, PMN functions (phagocytosis and oxidative burst), fluorescence in situ hybridization (FISH) analysis for any chromosomal abnormality, and T-cell receptor (TCR) clonal rearrangement by polymerase chain reaction (PCR) on bone marrow aspirate were performed. RESULTS: The patient’s clinical course was complicated by anemia requiring multiple blood transfusions, neutropenia requiring granulocytecolony stimulating factor, opportunistic infections, including cytomegalovirus retinitis and cutaneous fungal infections. Immunological analysis revealed pan hypogammaglobulinemia, a markedly increased CD3+CD8+ T cells, and low proportions of CD3-/CD16+/CD56+ (NK) cells, and CD3+/CD4+ T cells, and absence of CD19+ (B) cells. Specific antibody responses to pneumococcus polysaccharides were lacking. The response to mitogens (PHA, ConA, PWM) and recall antigens (Candida, tetanus toxoid, mumps) were severely impaired; neutrophil functions are normal. Bone marrow biopsy revealed T-cell LGL involving approximately 20% of hypercellular marrow confirmed by flow cytometry. Clonal rearrangements of both TCR-beta and gamma chains were detected by PCR, consistent with the diagnosis of T-cell LGL leukemia. FISH analysis was normal. CONCLUSIONS: To best of our knowledge this is the first case of T-cell LGL associated with Good’s syndrome. Patient was successfully treated with cyclophosphamide and cyclosporine (for LGL) and intravenous immunoglobulin (for antibody deficiency).
35
Recurrent Human Papillomavirus Infection and Delayed Diagnosis of Idiopathic CD4 Lymphocytopenia Michelle Korah-Sedgwick, MD, Kenneth Paris, MD, MPH; LSU Health Sciences Center, New Orleans, New Orleans, LA. RATIONALE: Idiopathic CD4 lymphopenia is a rare disorder featuring an isolated CD4 lymphopenia in the absence of precipitating infections, drugs, or any known etiology. Patients have persistently depressed CD4 counts, and commonly present with recurrent infections, malignancy, or autoimmune disease as a result. METHODS: Molecular diagnostic testing, flow cytometry, and chart review were performed. RESULTS: Patient A presented at the age of 43 with a 25 year history of recurrent infections. History included severe, recurrent HPV affecting the extremities and genital tract, as well as recurrent painful oral aphthous ulcers, recurrent subcutaneous scalp cysts, and persistent molluscum contagiosum, all recalcitrant to therapy. Family history was negative. CBC and evaluation of humoral immunity was normal, and HIV1/HIV2 and HTLV were negative. Other evaluations for newly identified immunodeficiencies were normal. Patient B presented at age 23 with a similar 3 year history of recurrent HPV to the extremities and genital tract, all recalcitrant to both topical and surgical therapy. Family history was negative. CBC and evaluation of humoral immunity was normal, and HIV1/HIV2 and HTLV were negative. Lymphocyte subpopulations were obtained for both patients on 2 occasions 6 weeks apart and notable for isolated CD4 lymphopenia. CONCLUSIONS: We present 2 cases of idiopathic CD4 lymphopenia with no identified precipitating etiologies. One case features a 25 year
history of recurrent infections that remained undiagnosed with a normal but limited immunological evaluation. These cases highlight that recurrent HPV infections continue to be a hallmark of this immunodeficiency, and should prompt more extensive immunological evaluation.
36
The Success of Newborn Screening for Severe Combined Immunodeficiency, Our Hospital's Experience Catherine D. Kubiak, MD1, Jessica R. Trotter, MA, BS2, Aleksandra Petrovic, MD3, Jennifer W. Leiding, MD2; 1University of South Florida, St Petersburg, FL, 2University of South Florida, St. Petersburg, FL, 3All Children’s Hospital, St. Petersburg, FL. RATIONALE: Severe combined immunodeficiency (SCID) is usually fatal due to serious infection in the first two years of life. Early detection is difficult due to the infant’s relative health initially maintained by maternal IgG. Diagnosis and treatment at an early age is less costly and more efficacious. Population based newborn screening (NBS) for SCID was added in Florida in 2012 with quantification of T cell receptor excision circles. We report the clinical outcome and cost analysis of two patients with SCID diagnosed in Florida. METHODS: Retrospective chart review of two patients diagnosed and treated for SCID at All Children’s Hospital was performed. Patient 1 was born just prior to SCID NBS in Florida; patient 2 was born shortly after. Hospital level of care, complications, treatments, and outcomes were collected as were financial charges including inpatient and outpatient visits up to 2 months post-hematopoietic stem cell transplant (HSCT). RESULTS: Patient 1 was 10 months when diagnosed with X-linked SCID after developing recurrent infections and failure to thrive. He spent 55 days in the critical care setting with multiple infections, respiratory failure, and died relatively quickly prior to HSCT. Patient 2 was diagnosed at 6 days of life with NBS and never required critical care. HSCT was performed without complication at 8 months. Total hospital days were 55 and 46 respectively. Combining all healthcare charges, patient 1 accrued $1,540,049 compared to $867,232 for patient 2. CONCLUSIONS: These two patients highlight the improved outcome and cost savings associated with NBS for SCID.
SATURDAY
Abstracts AB11
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Good's Syndrome Presenting As T-Cell Large Granular Lymphocyte Leukemia Caroline V. Caperton, MD, MSPH, Sudhir Gupta, MD, PhD, FAAAAI; Program in Primary Immunodeficiency and Aging, Division of Basic and Clinical Immunology, University of California School of Medicine, Irvine, CA. RATIONALE: Good Syndrome is an adult-onset immunodeficiency defined by hypogammaglobulinemia, low number of B cells, and benign thymic tumor. Rarely associated with malignancies. We report a case of Good’s syndrome that presented as T-cell Large granular lymphocytic leukemia (LGL). METHODS: Lymphocyte subset by flow cytometry, response to recall antigens and mitogens by 3H thymidine incorporation, PMN functions (phagocytosis and oxidative burst), fluorescence in situ hybridization (FISH) analysis for any chromosomal abnormality, and T-cell receptor (TCR) clonal rearrangement by polymerase chain reaction (PCR) on bone marrow aspirate were performed. RESULTS: The patient’s clinical course was complicated by anemia requiring multiple blood transfusions, neutropenia requiring granulocytecolony stimulating factor, opportunistic infections, including cytomegalovirus retinitis and cutaneous fungal infections. Immunological analysis revealed pan hypogammaglobulinemia, a markedly increased CD3+CD8+ T cells, and low proportions of CD3-/CD16+/CD56+ (NK) cells, and CD3+/CD4+ T cells, and absence of CD19+ (B) cells. Specific antibody responses to pneumococcus polysaccharides were lacking. The response to mitogens (PHA, ConA, PWM) and recall antigens (Candida, tetanus toxoid, mumps) were severely impaired; neutrophil functions are normal. Bone marrow biopsy revealed T-cell LGL involving approximately 20% of hypercellular marrow confirmed by flow cytometry. Clonal rearrangements of both TCR-beta and gamma chains were detected by PCR, consistent with the diagnosis of T-cell LGL leukemia. FISH analysis was normal. CONCLUSIONS: To best of our knowledge this is the first case of T-cell LGL associated with Good’s syndrome. Patient was successfully treated with cyclophosphamide and cyclosporine (for LGL) and intravenous immunoglobulin (for antibody deficiency).
35
Recurrent Human Papillomavirus Infection and Delayed Diagnosis of Idiopathic CD4 Lymphocytopenia Michelle Korah-Sedgwick, MD, Kenneth Paris, MD, MPH; LSU Health Sciences Center, New Orleans, New Orleans, LA. RATIONALE: Idiopathic CD4 lymphopenia is a rare disorder featuring an isolated CD4 lymphopenia in the absence of precipitating infections, drugs, or any known etiology. Patients have persistently depressed CD4 counts, and commonly present with recurrent infections, malignancy, or autoimmune disease as a result. METHODS: Molecular diagnostic testing, flow cytometry, and chart review were performed. RESULTS: Patient A presented at the age of 43 with a 25 year history of recurrent infections. History included severe, recurrent HPV affecting the extremities and genital tract, as well as recurrent painful oral aphthous ulcers, recurrent subcutaneous scalp cysts, and persistent molluscum contagiosum, all recalcitrant to therapy. Family history was negative. CBC and evaluation of humoral immunity was normal, and HIV1/HIV2 and HTLV were negative. Other evaluations for newly identified immunodeficiencies were normal. Patient B presented at age 23 with a similar 3 year history of recurrent HPV to the extremities and genital tract, all recalcitrant to both topical and surgical therapy. Family history was negative. CBC and evaluation of humoral immunity was normal, and HIV1/HIV2 and HTLV were negative. Lymphocyte subpopulations were obtained for both patients on 2 occasions 6 weeks apart and notable for isolated CD4 lymphopenia. CONCLUSIONS: We present 2 cases of idiopathic CD4 lymphopenia with no identified precipitating etiologies. One case features a 25 year
history of recurrent infections that remained undiagnosed with a normal but limited immunological evaluation. These cases highlight that recurrent HPV infections continue to be a hallmark of this immunodeficiency, and should prompt more extensive immunological evaluation.
36
The Success of Newborn Screening for Severe Combined Immunodeficiency, Our Hospital's Experience Catherine D. Kubiak, MD1, Jessica R. Trotter, MA, BS2, Aleksandra Petrovic, MD3, Jennifer W. Leiding, MD2; 1University of South Florida, St Petersburg, FL, 2University of South Florida, St. Petersburg, FL, 3All Children’s Hospital, St. Petersburg, FL. RATIONALE: Severe combined immunodeficiency (SCID) is usually fatal due to serious infection in the first two years of life. Early detection is difficult due to the infant’s relative health initially maintained by maternal IgG. Diagnosis and treatment at an early age is less costly and more efficacious. Population based newborn screening (NBS) for SCID was added in Florida in 2012 with quantification of T cell receptor excision circles. We report the clinical outcome and cost analysis of two patients with SCID diagnosed in Florida. METHODS: Retrospective chart review of two patients diagnosed and treated for SCID at All Children’s Hospital was performed. Patient 1 was born just prior to SCID NBS in Florida; patient 2 was born shortly after. Hospital level of care, complications, treatments, and outcomes were collected as were financial charges including inpatient and outpatient visits up to 2 months post-hematopoietic stem cell transplant (HSCT). RESULTS: Patient 1 was 10 months when diagnosed with X-linked SCID after developing recurrent infections and failure to thrive. He spent 55 days in the critical care setting with multiple infections, respiratory failure, and died relatively quickly prior to HSCT. Patient 2 was diagnosed at 6 days of life with NBS and never required critical care. HSCT was performed without complication at 8 months. Total hospital days were 55 and 46 respectively. Combining all healthcare charges, patient 1 accrued $1,540,049 compared to $867,232 for patient 2. CONCLUSIONS: These two patients highlight the improved outcome and cost savings associated with NBS for SCID.
SATURDAY
Abstracts AB11
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2