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Primary Selective IgM Deficiency (SIgMD) Associated With Functional Antibody Deficiency In Two Boys
S184 Abstracts
J ALLERGY CLIN IMMUNOL JANUARY 2007
because of subtle and nonspecific manifestations? It is important to identify patients with partial DGS not only to address their specific medical needs, but also for purposes of genetic counseling.
the level of defect. In patient-1 the presence of IgG in the absence of B-cells is counterintuitive. Functional antibody deficiency can coexist with SIgMD necessitating IVIG.
721
723
The Role of IVIG in Treatment of Hyper-IgE Syndrome (HIES) S. I. Krassilnikova, M. Davies, J. Rosch; Penn State’s Milton S. Hershey Medical Center, Hershey, PA. RATIONALE: Antimicrobial prophylaxis, skin care and the prompt treatment of infections have been the mainstay of treatment for patients with HIES. Despite these measures, recurrences of infections remain overwhelmingly high, revealing the limitations of current treatment strategies. IVIG has the potential to reduce the risk of infection. METHODS: We present a case of a 12 year-old boy with HIES, successfully treated with IVIG. We reviewed the literature on efficacy of IVIG in HIES patients using MEDLINE and PUBMED, keywords: HIES and IVIG. RESULTS: Our patient initially presented for evaluation of recurrent infections, asthma, and eczema at age 5. Physical examination revealed dermatitis and coarse facial features. His total IgE was 28,205 U/ml, but IgG, IgM and IgA levels were normal. Lymphocyte subset counts were: CD31 1121 cells/mm3 (1400-2200), CD81 287 (640-900), and normal CD41. Oxidative burst and delayed type hypersensitivity tests were normal. Pneumococcal titers remained low even after immunization. The patient continued to have recurrent sinusitis, otitis and pneumonia despite antibiotic prophylaxis prompting us to initiate IVIG at the age of 11. Since beginning IVIG he has not had recurrent infections, his overall health has significantly improved. Several published cases of HIES treated with IVIG have showed similar results. CONCLUSIONS: In patients with HIES humoral and cellular immune disregulations are present. Treatment with IVIG decreases the frequency of infections and may alter the immune dysfunction associated with HIES. Our experience and the evidence base in medical literature, suggest IVIG should be considered in the treatment of patients with HIES.
722
MONDAY
Primary Selective IgM Deficiency (SIgMD) Associated With Functional Antibody Deficiency In Two Boys F. I. Khan, M. Pansare, E. A. Secord; Carman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Detroit, MI. RATIONALE: SIgMD is a rare immunodeficiency with heterogeneous pathogenesis, clinical presentation and immunological profile. METHODS: Case reports. RESULTS: Patient-1: 7-year-old asthmatic having recurrent otitis, presented with pneumococal pneumonia and empyema requiring decortication. Investigation revealed deficient IgM and normal IgG/A/E. Antibody titers to polysaccharide and protein antigens were non-protective. B-cells were near-absent. T-cell subsets and NK-cell enumerations were normal. Monthly IVIG was started. The family became non-compliant with infusions for several months. Re-evaluation showed persistent IgM deficiency, B-cell absence, elevated IgE and normal IgG/A. Pre- and post-revaccination antibody titers remained suboptimal. IVIG was restarted. Four years later, patient developed chronic sinusitis and mild pleural-thickening. BTK-gene testing was done to evaluate B-cell absence. Patient-2: 18-month-old asthmatic with recurrent otitis presented with pseudomonal bronchopneumonia and sepsis requiring IVIG. This made vaccine titers non-interpretable. Investigation revealed panhypogammaglobulinemia. Lymphocyte enumeration and oxidative burst were normal. Monthly IVIG was started. Infusions ended secondary to non-adherence. Meanwhile a neutropenic febrile illness occurred. Re-evaluation showed deficient IgM, elevated IgE and normal IgG/A. Pre- and post-revaccination antibody titers to polysaccharide and protein antigens were non-protective. Monthly IVIG was reinstituted and patient thrived. Both patients were HIV-negative, normocomplementemic, had no isohemagglutinins or a family history of immunodeficiency. CONCLUSIONS: Defective B-cell istoype switching and altered T-cell helper/suppressor function have been implicated in the pathogenesis of SIgMD. In-vitro lymphocyte function assessment is needed to determine
14 Year Old Boy With ill-defined Immunodeficiency R. S. Watkins1, A. L. MacDowell1, M. Fontana-Penn1, S. De Ravin2, H. L. Malech2; 1Wake Forest University Baptist Med. Ctr., Winston Salem, NC, 2National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, MD. RATIONALE: Common Variable Immune Deficiency (CVID) is characterized by recurrent infections, reduced IgG, low levels of IgA and/or IgM, impaired antibody response and normal or mildly abnormal cellular immunity. Noncaseating granulomas are commonly seen in patients with CVID and can be misdiagnosed as sarcoidosis. METHODS: 14 year old boy presented at age 2 with recurrent infections, chronic diarrhea and family history of a sister with vague rheumatological complaints who died of staphylococcus aureus sepsis and lung abscesses at age 5. RESULTS: Evaluation revealed lymphopenia, IgG2 and IgG4 deficiency, and polysaccharide functional antibody deficiency. Despite IVIG, he continued to have recurrent infections and failure-to-thrive. Recently he presented with a rapidly enlarging palatal fistula. Biopsies of skin and sinuses showed noncaseating granulomas. This prompted a reassessment of his diagnosis. Evaluation off of IVIG for 4 months revealed lymphopenia (ALC: 1003/mm3), low IgG2 (<17 mg/ml) and IgG4 (<4 mg/ml) and no post-immunization response for tetanus and pneumococcus. Total IgG and IgA were normal and IgM was elevated (579 mg/dL). ANCA, ANA, NBT, DHR, HBV, HCV, HIV, ACE and sweat test were normal. Chest CT showed bronchiectasis and persistent hilar adenopathy. Possible diagnoses included CVID, sarcoid, malignancy, IPEX, Wegener’s granulomatosis and lethal midline granulomatous disease. The patient is currently receiving methotrexate, infliximab and prednisone to treat his granulomatous disease. CONCLUSIONS: We present an interesting patient whose clinic and laboratory results are a diagnostic puzzle. Our patient does not fulfill criteria for any known immunodeficiency or autoimmune disease and may represent a new clinical syndrome.
724
An Adolescent Patient with Chronic Granulomatous Disease (CGD) Presenting with Renal Failure P. D. Niolet, K. Paris, C. Moore; LSU Health Sciences Center, New Orleans, LA. RATIONALE: Patients with chronic granulomatous disease (CGD) have phagocytes that are unable to generate the oxidative burst necessary to kill catalase-positive bacteria and fungi. Patients are susceptible to subcutaneous and deep tissue abscesses, as well as invasive fungal infections. We report a case of a patient with CGD who presented with renal failure. METHODS: A 14 year-old boy presented to our emergency room with a 3-day history of vomiting and mental status changes. The patient was conscious, but uncooperative and disoriented. Blood pressure was 210/118 and he was afebrile. There were 3 subcutaneous abscesses present in the axilla, abdomen and right foot. Laboratory revealed BUN 125 and creatinine 45.5. WBC was 15,000 with a normal differential. Lumbar puncture, CT of the head, and hepatic functions were normal. RESULTS: The patient had been diagnosed with CGD elsewhere by dihydrorodamine assay six years previously but was lost to follow-up for two years. Ultrasound revealed small bilateral kidneys and no abscesses. He recovered with scheduled hemodialysis and is currently prophylaxed with trimethoprim/sulfamethoxazole. A maternal cousin also has CGD and a maternal uncle had recurrent abscesses prior to his death at 15 years. CONCLUSIONS: Chronic renal disease has been reported in association with CGD from the granulomata that occur in organ systems. However, the cause of this patient’s renal failure is still under investigation. This case emphasizes the need for close follow up of patients with an immunodeficiency and poses the challenge of performing a renal transplant in a patient with CGD.
J ALLERGY CLIN IMMUNOL JANUARY 2007
because of subtle and nonspecific manifestations? It is important to identify patients with partial DGS not only to address their specific medical needs, but also for purposes of genetic counseling.
the level of defect. In patient-1 the presence of IgG in the absence of B-cells is counterintuitive. Functional antibody deficiency can coexist with SIgMD necessitating IVIG.
721
723
The Role of IVIG in Treatment of Hyper-IgE Syndrome (HIES) S. I. Krassilnikova, M. Davies, J. Rosch; Penn State’s Milton S. Hershey Medical Center, Hershey, PA. RATIONALE: Antimicrobial prophylaxis, skin care and the prompt treatment of infections have been the mainstay of treatment for patients with HIES. Despite these measures, recurrences of infections remain overwhelmingly high, revealing the limitations of current treatment strategies. IVIG has the potential to reduce the risk of infection. METHODS: We present a case of a 12 year-old boy with HIES, successfully treated with IVIG. We reviewed the literature on efficacy of IVIG in HIES patients using MEDLINE and PUBMED, keywords: HIES and IVIG. RESULTS: Our patient initially presented for evaluation of recurrent infections, asthma, and eczema at age 5. Physical examination revealed dermatitis and coarse facial features. His total IgE was 28,205 U/ml, but IgG, IgM and IgA levels were normal. Lymphocyte subset counts were: CD31 1121 cells/mm3 (1400-2200), CD81 287 (640-900), and normal CD41. Oxidative burst and delayed type hypersensitivity tests were normal. Pneumococcal titers remained low even after immunization. The patient continued to have recurrent sinusitis, otitis and pneumonia despite antibiotic prophylaxis prompting us to initiate IVIG at the age of 11. Since beginning IVIG he has not had recurrent infections, his overall health has significantly improved. Several published cases of HIES treated with IVIG have showed similar results. CONCLUSIONS: In patients with HIES humoral and cellular immune disregulations are present. Treatment with IVIG decreases the frequency of infections and may alter the immune dysfunction associated with HIES. Our experience and the evidence base in medical literature, suggest IVIG should be considered in the treatment of patients with HIES.
722
MONDAY
Primary Selective IgM Deficiency (SIgMD) Associated With Functional Antibody Deficiency In Two Boys F. I. Khan, M. Pansare, E. A. Secord; Carman and Ann Adams Department of Pediatrics, Children’s Hospital of Michigan, Detroit, MI. RATIONALE: SIgMD is a rare immunodeficiency with heterogeneous pathogenesis, clinical presentation and immunological profile. METHODS: Case reports. RESULTS: Patient-1: 7-year-old asthmatic having recurrent otitis, presented with pneumococal pneumonia and empyema requiring decortication. Investigation revealed deficient IgM and normal IgG/A/E. Antibody titers to polysaccharide and protein antigens were non-protective. B-cells were near-absent. T-cell subsets and NK-cell enumerations were normal. Monthly IVIG was started. The family became non-compliant with infusions for several months. Re-evaluation showed persistent IgM deficiency, B-cell absence, elevated IgE and normal IgG/A. Pre- and post-revaccination antibody titers remained suboptimal. IVIG was restarted. Four years later, patient developed chronic sinusitis and mild pleural-thickening. BTK-gene testing was done to evaluate B-cell absence. Patient-2: 18-month-old asthmatic with recurrent otitis presented with pseudomonal bronchopneumonia and sepsis requiring IVIG. This made vaccine titers non-interpretable. Investigation revealed panhypogammaglobulinemia. Lymphocyte enumeration and oxidative burst were normal. Monthly IVIG was started. Infusions ended secondary to non-adherence. Meanwhile a neutropenic febrile illness occurred. Re-evaluation showed deficient IgM, elevated IgE and normal IgG/A. Pre- and post-revaccination antibody titers to polysaccharide and protein antigens were non-protective. Monthly IVIG was reinstituted and patient thrived. Both patients were HIV-negative, normocomplementemic, had no isohemagglutinins or a family history of immunodeficiency. CONCLUSIONS: Defective B-cell istoype switching and altered T-cell helper/suppressor function have been implicated in the pathogenesis of SIgMD. In-vitro lymphocyte function assessment is needed to determine
14 Year Old Boy With ill-defined Immunodeficiency R. S. Watkins1, A. L. MacDowell1, M. Fontana-Penn1, S. De Ravin2, H. L. Malech2; 1Wake Forest University Baptist Med. Ctr., Winston Salem, NC, 2National Institute of Allergy and Infectious Diseases; National Institutes of Health, Bethesda, MD. RATIONALE: Common Variable Immune Deficiency (CVID) is characterized by recurrent infections, reduced IgG, low levels of IgA and/or IgM, impaired antibody response and normal or mildly abnormal cellular immunity. Noncaseating granulomas are commonly seen in patients with CVID and can be misdiagnosed as sarcoidosis. METHODS: 14 year old boy presented at age 2 with recurrent infections, chronic diarrhea and family history of a sister with vague rheumatological complaints who died of staphylococcus aureus sepsis and lung abscesses at age 5. RESULTS: Evaluation revealed lymphopenia, IgG2 and IgG4 deficiency, and polysaccharide functional antibody deficiency. Despite IVIG, he continued to have recurrent infections and failure-to-thrive. Recently he presented with a rapidly enlarging palatal fistula. Biopsies of skin and sinuses showed noncaseating granulomas. This prompted a reassessment of his diagnosis. Evaluation off of IVIG for 4 months revealed lymphopenia (ALC: 1003/mm3), low IgG2 (<17 mg/ml) and IgG4 (<4 mg/ml) and no post-immunization response for tetanus and pneumococcus. Total IgG and IgA were normal and IgM was elevated (579 mg/dL). ANCA, ANA, NBT, DHR, HBV, HCV, HIV, ACE and sweat test were normal. Chest CT showed bronchiectasis and persistent hilar adenopathy. Possible diagnoses included CVID, sarcoid, malignancy, IPEX, Wegener’s granulomatosis and lethal midline granulomatous disease. The patient is currently receiving methotrexate, infliximab and prednisone to treat his granulomatous disease. CONCLUSIONS: We present an interesting patient whose clinic and laboratory results are a diagnostic puzzle. Our patient does not fulfill criteria for any known immunodeficiency or autoimmune disease and may represent a new clinical syndrome.
724
An Adolescent Patient with Chronic Granulomatous Disease (CGD) Presenting with Renal Failure P. D. Niolet, K. Paris, C. Moore; LSU Health Sciences Center, New Orleans, LA. RATIONALE: Patients with chronic granulomatous disease (CGD) have phagocytes that are unable to generate the oxidative burst necessary to kill catalase-positive bacteria and fungi. Patients are susceptible to subcutaneous and deep tissue abscesses, as well as invasive fungal infections. We report a case of a patient with CGD who presented with renal failure. METHODS: A 14 year-old boy presented to our emergency room with a 3-day history of vomiting and mental status changes. The patient was conscious, but uncooperative and disoriented. Blood pressure was 210/118 and he was afebrile. There were 3 subcutaneous abscesses present in the axilla, abdomen and right foot. Laboratory revealed BUN 125 and creatinine 45.5. WBC was 15,000 with a normal differential. Lumbar puncture, CT of the head, and hepatic functions were normal. RESULTS: The patient had been diagnosed with CGD elsewhere by dihydrorodamine assay six years previously but was lost to follow-up for two years. Ultrasound revealed small bilateral kidneys and no abscesses. He recovered with scheduled hemodialysis and is currently prophylaxed with trimethoprim/sulfamethoxazole. A maternal cousin also has CGD and a maternal uncle had recurrent abscesses prior to his death at 15 years. CONCLUSIONS: Chronic renal disease has been reported in association with CGD from the granulomata that occur in organ systems. However, the cause of this patient’s renal failure is still under investigation. This case emphasizes the need for close follow up of patients with an immunodeficiency and poses the challenge of performing a renal transplant in a patient with CGD.