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Immune deficiency in VACTERL syndrome complicating chylothorax
Abstracts S229
J ALLERGY CLIN IMMUNOL VOLUME 111, NUMBER 2
39 Von Willebrand Disease Type III and Diminished Responseto 641 Trimethoprim-Sulfamethoxazole (TMP-SMX)--Associated NeuBacteriophage phiX174Testing tropenia in a Patient with X-linked Hyper IgM Syndrome I', H. Sher j , N. Wasserbauer2, R. W. Hostoffer, Jr.3; ICase Western Reserve University, Highland Heights, OH, 2Chicago College of Osteopathic Medicine, Chicago, IL, 3Case Western Reserve University, Cleveland, OH. RATIONALE: The association of bleeding disorders and acquired immunodeficiency has been described, although primary immunodeficiencies have not. We report a case of a 6yo child with Von Willebrand's Disease (vWd) Type Ili and a primary antibody production deficiency. METHODS: AM is the 6yo white female product and twin A of a normal twin gestation pregnancy. Her first middle ear infection was experienced at 7 wks of life. At 4 months of life she developed a periorbital hematoma and was subsequently diagnosed with vWd. Thereafter we document 47 episodes of otitis media, 3 episodes of Bronchiolitis/URl, and 3 central line infections. RESULTS: She has a normal response to pneumococcal, tetanus and diphtheria vaccination, suggesting a normal T-cell dependent and T-cell independent response, respectively. Serum immunoglobulin levels are normal with IgGl at 706 mg/dL (330-1065 mg/dL), IgG2 at 218 mg/dL (57-345), lgG3 at 50 mg/dL (8-126 mg/dL), IgG4 at <1. Total IgG was measured at 1020 mg/dL (460-1280 mg/dL), also within normal limits. Neutrophils were found to be normal in migration and superoxide production. Metabolic testing has proven to be normal. Testing of AM's immune system via bacteriophage vaccination showed that her primary immunization response was low and her secondary immunization responses were subnormal. The patient was placed on monthly IvlgG beginning July 2002. She has been infection free since this time. CONCLUSIONS: This case presents the association of a homozygous bleeding disorder associated with an antibody production deficiency defined by bacteriophage testing.
Funding: Self-funded
640 IothoraxlmmuneDeficiency in VACTERLSyndrome Complicating ChyN. Kashemsri j, K. E. Georgeson 2, T. P. Atkinsonl; rPediatrics, University of Alabama at Birmingham, Birmingham, AL, 2Surgery, University of Alabama at Birmingham, Birmingham, AL. RATIONALE: Immune deficiency following thoracic duct laceration is not well known. We report a case of VACTERL syndrome who developed immune deficiency alter severe thoracic duct laceration. M E T H O D S : We serially evaluated quantitative immunoglobulins, peripheral blood lymphocyte subpopulations by flow cytometry and antibody responses to vaccines in a VACTERL syndrome patient, who developed immune deficiency associated with a post-operative chylothorax, over the course of one year. RESULTS: A newborn infant with VACTERL syndrome (distal tracheoesophageal fistula and proximal esophageal atresia, patent ductus arteriosus, coarctation of aorta, vertebral anomalies) developed a left chylothorax following a thoracoscopic repair of tracheoesophageal fistula on the day she was born. At one month of age, following two subsequent surgeries, she developed sepsis with Candida parapsilopsis and Staphylococcus epidermidis. Her circulating B lymphocytes were markedly decreased at 93/ram 3 (2%) with normal circulating T cell numbers and distribution (absolute T lymphocytes 2430/mm 3, CD4/CD8 ratio 2.3). At six weeks of age, her absolute B lymphocytes were still low: 223/mm 3 (4%) with normal T lymphocytes (3,706/mm 3 (CD4/CD8 ratio 1.7)). Immunoglobulin M was depressed for age: lgM < 4, IgA 4, IgG 610, IgE 4. After broad spectrum antibiotics and IVIG, she recovered. When she was four months old, immunoglobulins revealed continued hypogammaglobulinemia and improving B cell lymphopenia: IgG 231, lgA 6, lgM 6, absolute B cells 767/mm 3 (7%), absolute T cells 3,718/mm 3 (CD4/CD8 ratio 1.8). This gradual improvement has continued. CONCLUSIONS: Thoracic duct laceration early in life may result in selective B cell deficiency.
Funding: Self funded
(XHIM) D. B. Coyle, M. B. Fasano; Allergy/Immunology, Wake Forest University School of Medicine, Winston-Salem, NC. RATIONALE: While neutropenia may represent a portion of the clinical spectrum of XHIM, these patients are also at risk for iatrogenic neutropenia secondary to PCP prophylaxis with TMP-SMX. METHODS: We present a case of TMP-SMX induced neutropenia in a patient with XHIM. A 23 month old male child presented with recurrent neck abscesses and was found to have decreased IgG and IgA, elevated IgM, and normal neutrophil, platelet, T, B, and NK cell numbers. T cell response to mitogens was normal, while antibody responses to tetanus and HIB were poor. FACS analysis of PBMC revealed poor expression of CD40L and DNA analysis revealed a missense mutation affecting the extracellular domain of CD40L, establishing the diagnosis of XHIM. Patient was started on 1V1G therapy and began PCP prophylaxis with TMP-SMX. RESULTS: Two temporally distinct trials on TMP-SMX therapy at 150 mg/m2/day divided q l2 hours three days a week resulted in acute neutropenia (ANC 600 and 100) with prompt resolution upon cessation of TMP-SMX. Patient currently on Dapsone prophylaxis (4 mg/kg/day once weekly) and ANC stable over 1500. CONCLUSIONS: While neutropenia can be commonly associated with XHIM (up to 67.8%), TMP-SMX induced neutropenia is also well documented in the medical literature and should also be considered in the XHIM population, especially if neutropenia is not a part of the clinical picture until after PCP prophylaxis is instituted. Perhaps this population is at greater risk for TMP-SMX neutropenia.
642 Trisomy18 Associated with CombinedImmune Deficiency E O. Seeborg, W. T. Shearer, L. M. Noroski; Texas Children's Hospital, Allergy & Immunology, Baylor College of Medicine, Houston, TX. I N T R O D U C T I O N : Trisomy 18 is the second most common multiple malformation syndrome consisting of skeletal, cardiac, renal, neurological and skirl abnormalities. No reported immune deficiency associated with Trisomy 18 in surviving children is in the literature. CASE REPORT: We report a 28 month old female with Trisomy 18 and immunological abnormalities who has had pneumonias, reactive airway disease and seizure disorder. Immune parameters repeatedly revealed profoundly low serum IgG, low IgA and lgM. Fecal alfa-I antitrypsin was normal despite low total serum proteins. Antibody responses to protein antigens were adequate. Antipolysaccharide levels were depressed. Lymphocyte studies revealed low CD3, CD4, CD8 percentages and normal numbers, and high percentages/numbers of CD 20 for age. In vitro lymphoproliferative responses to mitogens and antigens and FISH tbr DiGeorge were normal. D I S C U S S I O N : A variable complex of immunological alterations described in Trisomy 21 consist of cellular immune defects. In deletion of chromosome 18, lgA deficiency can occur. Thymic and ovarian hypoplasia have been described in numerical and structural anomalies of chromosome 18. However no known particular immune defect is defined in Trisomy 18. Panhypogammaglobulinemia and partial defective humoral response with elevated CD20 counts may be transient maturational arrest and a B cell compensatory mechanism. T lymphocyte alterations may be explained by possible thymic hypoplasia. CONCLUSION: Immunological and clinical phenotype of Trisomy 18 may represent part of the same spectrum of other chromosome 18 detects where thymic abnormalities have been described. With lengthened survival in "lethal diseases," immunodeficiencies that were not previously described may be uncovered.
Funding: Texas Children's Hospital
J ALLERGY CLIN IMMUNOL VOLUME 111, NUMBER 2
39 Von Willebrand Disease Type III and Diminished Responseto 641 Trimethoprim-Sulfamethoxazole (TMP-SMX)--Associated NeuBacteriophage phiX174Testing tropenia in a Patient with X-linked Hyper IgM Syndrome I', H. Sher j , N. Wasserbauer2, R. W. Hostoffer, Jr.3; ICase Western Reserve University, Highland Heights, OH, 2Chicago College of Osteopathic Medicine, Chicago, IL, 3Case Western Reserve University, Cleveland, OH. RATIONALE: The association of bleeding disorders and acquired immunodeficiency has been described, although primary immunodeficiencies have not. We report a case of a 6yo child with Von Willebrand's Disease (vWd) Type Ili and a primary antibody production deficiency. METHODS: AM is the 6yo white female product and twin A of a normal twin gestation pregnancy. Her first middle ear infection was experienced at 7 wks of life. At 4 months of life she developed a periorbital hematoma and was subsequently diagnosed with vWd. Thereafter we document 47 episodes of otitis media, 3 episodes of Bronchiolitis/URl, and 3 central line infections. RESULTS: She has a normal response to pneumococcal, tetanus and diphtheria vaccination, suggesting a normal T-cell dependent and T-cell independent response, respectively. Serum immunoglobulin levels are normal with IgGl at 706 mg/dL (330-1065 mg/dL), IgG2 at 218 mg/dL (57-345), lgG3 at 50 mg/dL (8-126 mg/dL), IgG4 at <1. Total IgG was measured at 1020 mg/dL (460-1280 mg/dL), also within normal limits. Neutrophils were found to be normal in migration and superoxide production. Metabolic testing has proven to be normal. Testing of AM's immune system via bacteriophage vaccination showed that her primary immunization response was low and her secondary immunization responses were subnormal. The patient was placed on monthly IvlgG beginning July 2002. She has been infection free since this time. CONCLUSIONS: This case presents the association of a homozygous bleeding disorder associated with an antibody production deficiency defined by bacteriophage testing.
Funding: Self-funded
640 IothoraxlmmuneDeficiency in VACTERLSyndrome Complicating ChyN. Kashemsri j, K. E. Georgeson 2, T. P. Atkinsonl; rPediatrics, University of Alabama at Birmingham, Birmingham, AL, 2Surgery, University of Alabama at Birmingham, Birmingham, AL. RATIONALE: Immune deficiency following thoracic duct laceration is not well known. We report a case of VACTERL syndrome who developed immune deficiency alter severe thoracic duct laceration. M E T H O D S : We serially evaluated quantitative immunoglobulins, peripheral blood lymphocyte subpopulations by flow cytometry and antibody responses to vaccines in a VACTERL syndrome patient, who developed immune deficiency associated with a post-operative chylothorax, over the course of one year. RESULTS: A newborn infant with VACTERL syndrome (distal tracheoesophageal fistula and proximal esophageal atresia, patent ductus arteriosus, coarctation of aorta, vertebral anomalies) developed a left chylothorax following a thoracoscopic repair of tracheoesophageal fistula on the day she was born. At one month of age, following two subsequent surgeries, she developed sepsis with Candida parapsilopsis and Staphylococcus epidermidis. Her circulating B lymphocytes were markedly decreased at 93/ram 3 (2%) with normal circulating T cell numbers and distribution (absolute T lymphocytes 2430/mm 3, CD4/CD8 ratio 2.3). At six weeks of age, her absolute B lymphocytes were still low: 223/mm 3 (4%) with normal T lymphocytes (3,706/mm 3 (CD4/CD8 ratio 1.7)). Immunoglobulin M was depressed for age: lgM < 4, IgA 4, IgG 610, IgE 4. After broad spectrum antibiotics and IVIG, she recovered. When she was four months old, immunoglobulins revealed continued hypogammaglobulinemia and improving B cell lymphopenia: IgG 231, lgA 6, lgM 6, absolute B cells 767/mm 3 (7%), absolute T cells 3,718/mm 3 (CD4/CD8 ratio 1.8). This gradual improvement has continued. CONCLUSIONS: Thoracic duct laceration early in life may result in selective B cell deficiency.
Funding: Self funded
(XHIM) D. B. Coyle, M. B. Fasano; Allergy/Immunology, Wake Forest University School of Medicine, Winston-Salem, NC. RATIONALE: While neutropenia may represent a portion of the clinical spectrum of XHIM, these patients are also at risk for iatrogenic neutropenia secondary to PCP prophylaxis with TMP-SMX. METHODS: We present a case of TMP-SMX induced neutropenia in a patient with XHIM. A 23 month old male child presented with recurrent neck abscesses and was found to have decreased IgG and IgA, elevated IgM, and normal neutrophil, platelet, T, B, and NK cell numbers. T cell response to mitogens was normal, while antibody responses to tetanus and HIB were poor. FACS analysis of PBMC revealed poor expression of CD40L and DNA analysis revealed a missense mutation affecting the extracellular domain of CD40L, establishing the diagnosis of XHIM. Patient was started on 1V1G therapy and began PCP prophylaxis with TMP-SMX. RESULTS: Two temporally distinct trials on TMP-SMX therapy at 150 mg/m2/day divided q l2 hours three days a week resulted in acute neutropenia (ANC 600 and 100) with prompt resolution upon cessation of TMP-SMX. Patient currently on Dapsone prophylaxis (4 mg/kg/day once weekly) and ANC stable over 1500. CONCLUSIONS: While neutropenia can be commonly associated with XHIM (up to 67.8%), TMP-SMX induced neutropenia is also well documented in the medical literature and should also be considered in the XHIM population, especially if neutropenia is not a part of the clinical picture until after PCP prophylaxis is instituted. Perhaps this population is at greater risk for TMP-SMX neutropenia.
642 Trisomy18 Associated with CombinedImmune Deficiency E O. Seeborg, W. T. Shearer, L. M. Noroski; Texas Children's Hospital, Allergy & Immunology, Baylor College of Medicine, Houston, TX. I N T R O D U C T I O N : Trisomy 18 is the second most common multiple malformation syndrome consisting of skeletal, cardiac, renal, neurological and skirl abnormalities. No reported immune deficiency associated with Trisomy 18 in surviving children is in the literature. CASE REPORT: We report a 28 month old female with Trisomy 18 and immunological abnormalities who has had pneumonias, reactive airway disease and seizure disorder. Immune parameters repeatedly revealed profoundly low serum IgG, low IgA and lgM. Fecal alfa-I antitrypsin was normal despite low total serum proteins. Antibody responses to protein antigens were adequate. Antipolysaccharide levels were depressed. Lymphocyte studies revealed low CD3, CD4, CD8 percentages and normal numbers, and high percentages/numbers of CD 20 for age. In vitro lymphoproliferative responses to mitogens and antigens and FISH tbr DiGeorge were normal. D I S C U S S I O N : A variable complex of immunological alterations described in Trisomy 21 consist of cellular immune defects. In deletion of chromosome 18, lgA deficiency can occur. Thymic and ovarian hypoplasia have been described in numerical and structural anomalies of chromosome 18. However no known particular immune defect is defined in Trisomy 18. Panhypogammaglobulinemia and partial defective humoral response with elevated CD20 counts may be transient maturational arrest and a B cell compensatory mechanism. T lymphocyte alterations may be explained by possible thymic hypoplasia. CONCLUSION: Immunological and clinical phenotype of Trisomy 18 may represent part of the same spectrum of other chromosome 18 detects where thymic abnormalities have been described. With lengthened survival in "lethal diseases," immunodeficiencies that were not previously described may be uncovered.
Funding: Texas Children's Hospital