- Email: [email protected]
Adjunctive Hyperbaric Oxygen Therapy (HBOT) in Patients with Primary Immunodeficiency
Abstracts AB183
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Prompt Diagnosis of Autosomal Dominant Hyper IgE Syndrome Leads to Reduced Infection and Improved Clinical Phenotype Kelli W. Williams, MD, MPH1, Katherine McGowan, BS1, Kathryn J. Sowerwine, MD2, Joie Davis, PNP1, Steven M. Holland, MD1, Alexandra F. Freeman, MD3; 1Laboratory of Clinical Infectious Diseases, NIAID/NIH, Bethesda, MD, 2Dermatology Specialists of Virgnia, Reston, VA, 3NIH/NIAID, Laboratory of Clinical Infectious Diseases, Bethesda, MD. RATIONALE: Dominant negative mutations in STAT3 lead to elevated serum IgE, eczema, and recurrent skin and lung infections, known as autosomal dominant Hyper IgE Syndrome (AD-HIES). We aimed to characterize the phenotype of AD-HIES diagnosed in infancy and the impact of early diagnosis. METHODS: We retrospectively reviewed 16 subjects referred for ADHIES before age 2 years. Demographic, clinical and laboratory data concerning diagnosis and treatment were collected and compared between children with and without a family history of AD-HIES. RESULTS: Sixteen patients were diagnosed with AD-HIES before age 2 years, with 9 (56%) having a known family history. The median diagnosis age was 5.8 months and comparable between groups. Antibacterial prophylaxis was started in 94% and antifungal prophylaxis in 32% of the 16 patients. Nine of the 16 (56%) had documented skin abscesses: 5 probands and 4 with family history. All 7 probands had at least one pneumonia with 43% first presenting with Pneumocystis jiroveci. Six (67%) with family history had pneumonia. Newborn rash and eczema were common; severity was worse in probands. At current ages 1.3-30 years, 3 have pneumatoceles and 1 has bronchiectasis. Four of the 9 (current ages 1.3-6.6 years) with a family history were diagnosed genetically as newborns before symptoms developed and had antiseptic baths and antibacterial prophylaxis initiated in the first months of life. None reported skin abscesses or bacterial pneumonia, and eczema was mild. CONCLUSIONS: Prompt diagnosis of AD-HIES leads to earlier initiation of antibacterial prophylaxis and antiseptics, which are effective at reducing infection and improve clinical phenotype.
591
Improvement of Recurrent Infections after IVIG Supplementation in a Patient with Leukocyte Adhesion Deficiency III with a Novel Missense Mutation in FERMT3 Narissara Suratannon, MD1,2, Patra Yeetong3,4, Chalurmpon Srichomthon3,4, Pantipa Chatchatee, MD2, Martin van Hagen1,5, Gertjan J. Driessen1,6, Mirjam van der Burg1, Darintr Sosothikul7, Jarungchit Ngamphaiboon, MD2, Kanya Suphapeetiporn3,4, Vorasuk Shotelersuk3,4; 1 Departments of Immunology, Erasmus MC, Rotterdam, Netherlands, 2 Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 3Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand, 4Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 5Departments of Internal Medicine, Erasmus MC, Rotterdam, Netherlands, 6Departments of Pediatric Infectious Disease and Immunology, Erasmus MC, Rotterdam, Netherlands, 7Division of Pediatric Hematology/Oncology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. RATIONALE: Leukocyte adhesion defect type III (LAD-III) is a rare primary immunodeficiency disorder. The cause is from mutation in FERMT3 leading to functional defects of integrins. Its main clinical features are from phagocytic dysfunctions. Although integrins present on the surface of T and B lymphocytes, defective adaptive immune functions have been rarely reported. Nowadays, bone marrow transplantation is only a definite treatment. Here we reported a girl with LAD-III who had
significant decreased of recurrent infections after intravenous immunoglobulin (IVIG) supplementation. METHODS: Molecular characterization was performed by exome sequencing. Western blotting of FERMT3 protein was analyzed. Flow cytometric analyses of T and B cell subset and neutrophil were measured. RESULTS: The patient presented with recurrent life-threatening infections, osteopetrosis and impaired wound healing starting at 2 months old. Mutation analysis confirmed homozygous novel missense mutation in FERMT3. Besides persistent leukocytosis and impaired platelet aggregation which are the classic phenotypes, she had low immunoglobulin levels. Flow cytometry revealed low percentages of class switching memory B cells(CD27+IgD-), marginal zone–like B cells(CD27+IgD+IgM+),CD27- memory B cells (CD27IgD-), and plasmablast(CD24-CD38hi). IVIG replacement leads to a significant reduction in episodes of infection and eventually no infection for the 3 years of follow up. CONCLUSIONS: Patient with LAD-III may have associated humeral immune defect. Our study emphasized the importance of adaptive immune defect contributing to recurrent infections in the patient. Adaptive immune function especially serum immunoglobulins should be evaluated in patients with LAD-III. IVIG can be considered as an alternative treatment or as an adjunctive treatment while waiting for bone marrow transplantation.
592
Adjunctive Hyperbaric Oxygen Therapy (HBOT) in Patients with Primary Immunodeficiency Lorena R. Pereira, MD1, Daniel H. Conway, MD2; 1Duke University Medical Center, Durham, NC, 2St. Christopher’s Hospital for Children, Philadelphia, PA. RATIONALE: Wound healing is a carefully orchestrated process involving many cell players including cytokines and growth factors. It has been observed that suppressed immune function results in delayed unorganized tissue repair. Benefits of adjunctive HBOT include enhancement of cellular defenses, toxicity to anaerobes and increased leukocyte cidal activity. Here we describe 2 patients with primary immunodeficiency who received adjunctive HBOT in conjunction to wound care to accelerate the wound repair process. METHODS: Effects of HBOT on wound healing in two female patients aged 9 and 17 years with primary immunodeficiency and necrotizing fasciitis were reviewed. RESULTS: These case presentations highlight the role of HBOT in the immune compromised host. HBOT was effective in promoting wound healing which is impaired in these patients. Furthermore HBOT was safe; neither of the patients had any adverse effects related to the HBOT. CONCLUSIONS: Reports of the use HBOT are unusual in wound infections complicating primary immunodeficiency. We found HBOT to be beneficial in promoting soft tissue healing in these two patients. Additionally, this adjunctive therapy was safe, with no adverse effects. Because of the delayed healing and the complications that accompany soft tissue infections in the immune compromised host, adjunctive treatments such as HBOT should be considered.
MONDAY
590
J ALLERGY CLIN IMMUNOL VOLUME 135, NUMBER 2
Prompt Diagnosis of Autosomal Dominant Hyper IgE Syndrome Leads to Reduced Infection and Improved Clinical Phenotype Kelli W. Williams, MD, MPH1, Katherine McGowan, BS1, Kathryn J. Sowerwine, MD2, Joie Davis, PNP1, Steven M. Holland, MD1, Alexandra F. Freeman, MD3; 1Laboratory of Clinical Infectious Diseases, NIAID/NIH, Bethesda, MD, 2Dermatology Specialists of Virgnia, Reston, VA, 3NIH/NIAID, Laboratory of Clinical Infectious Diseases, Bethesda, MD. RATIONALE: Dominant negative mutations in STAT3 lead to elevated serum IgE, eczema, and recurrent skin and lung infections, known as autosomal dominant Hyper IgE Syndrome (AD-HIES). We aimed to characterize the phenotype of AD-HIES diagnosed in infancy and the impact of early diagnosis. METHODS: We retrospectively reviewed 16 subjects referred for ADHIES before age 2 years. Demographic, clinical and laboratory data concerning diagnosis and treatment were collected and compared between children with and without a family history of AD-HIES. RESULTS: Sixteen patients were diagnosed with AD-HIES before age 2 years, with 9 (56%) having a known family history. The median diagnosis age was 5.8 months and comparable between groups. Antibacterial prophylaxis was started in 94% and antifungal prophylaxis in 32% of the 16 patients. Nine of the 16 (56%) had documented skin abscesses: 5 probands and 4 with family history. All 7 probands had at least one pneumonia with 43% first presenting with Pneumocystis jiroveci. Six (67%) with family history had pneumonia. Newborn rash and eczema were common; severity was worse in probands. At current ages 1.3-30 years, 3 have pneumatoceles and 1 has bronchiectasis. Four of the 9 (current ages 1.3-6.6 years) with a family history were diagnosed genetically as newborns before symptoms developed and had antiseptic baths and antibacterial prophylaxis initiated in the first months of life. None reported skin abscesses or bacterial pneumonia, and eczema was mild. CONCLUSIONS: Prompt diagnosis of AD-HIES leads to earlier initiation of antibacterial prophylaxis and antiseptics, which are effective at reducing infection and improve clinical phenotype.
591
Improvement of Recurrent Infections after IVIG Supplementation in a Patient with Leukocyte Adhesion Deficiency III with a Novel Missense Mutation in FERMT3 Narissara Suratannon, MD1,2, Patra Yeetong3,4, Chalurmpon Srichomthon3,4, Pantipa Chatchatee, MD2, Martin van Hagen1,5, Gertjan J. Driessen1,6, Mirjam van der Burg1, Darintr Sosothikul7, Jarungchit Ngamphaiboon, MD2, Kanya Suphapeetiporn3,4, Vorasuk Shotelersuk3,4; 1 Departments of Immunology, Erasmus MC, Rotterdam, Netherlands, 2 Division of Allergy and Immunology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 3Excellence Center for Medical Genetics, King Chulalongkorn Memorial Hospital, the Thai Red Cross Society, Bangkok, Thailand, 4Center of Excellence for Medical Genetics, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand, 5Departments of Internal Medicine, Erasmus MC, Rotterdam, Netherlands, 6Departments of Pediatric Infectious Disease and Immunology, Erasmus MC, Rotterdam, Netherlands, 7Division of Pediatric Hematology/Oncology, Department of Pediatrics, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. RATIONALE: Leukocyte adhesion defect type III (LAD-III) is a rare primary immunodeficiency disorder. The cause is from mutation in FERMT3 leading to functional defects of integrins. Its main clinical features are from phagocytic dysfunctions. Although integrins present on the surface of T and B lymphocytes, defective adaptive immune functions have been rarely reported. Nowadays, bone marrow transplantation is only a definite treatment. Here we reported a girl with LAD-III who had
significant decreased of recurrent infections after intravenous immunoglobulin (IVIG) supplementation. METHODS: Molecular characterization was performed by exome sequencing. Western blotting of FERMT3 protein was analyzed. Flow cytometric analyses of T and B cell subset and neutrophil were measured. RESULTS: The patient presented with recurrent life-threatening infections, osteopetrosis and impaired wound healing starting at 2 months old. Mutation analysis confirmed homozygous novel missense mutation in FERMT3. Besides persistent leukocytosis and impaired platelet aggregation which are the classic phenotypes, she had low immunoglobulin levels. Flow cytometry revealed low percentages of class switching memory B cells(CD27+IgD-), marginal zone–like B cells(CD27+IgD+IgM+),CD27- memory B cells (CD27IgD-), and plasmablast(CD24-CD38hi). IVIG replacement leads to a significant reduction in episodes of infection and eventually no infection for the 3 years of follow up. CONCLUSIONS: Patient with LAD-III may have associated humeral immune defect. Our study emphasized the importance of adaptive immune defect contributing to recurrent infections in the patient. Adaptive immune function especially serum immunoglobulins should be evaluated in patients with LAD-III. IVIG can be considered as an alternative treatment or as an adjunctive treatment while waiting for bone marrow transplantation.
592
Adjunctive Hyperbaric Oxygen Therapy (HBOT) in Patients with Primary Immunodeficiency Lorena R. Pereira, MD1, Daniel H. Conway, MD2; 1Duke University Medical Center, Durham, NC, 2St. Christopher’s Hospital for Children, Philadelphia, PA. RATIONALE: Wound healing is a carefully orchestrated process involving many cell players including cytokines and growth factors. It has been observed that suppressed immune function results in delayed unorganized tissue repair. Benefits of adjunctive HBOT include enhancement of cellular defenses, toxicity to anaerobes and increased leukocyte cidal activity. Here we describe 2 patients with primary immunodeficiency who received adjunctive HBOT in conjunction to wound care to accelerate the wound repair process. METHODS: Effects of HBOT on wound healing in two female patients aged 9 and 17 years with primary immunodeficiency and necrotizing fasciitis were reviewed. RESULTS: These case presentations highlight the role of HBOT in the immune compromised host. HBOT was effective in promoting wound healing which is impaired in these patients. Furthermore HBOT was safe; neither of the patients had any adverse effects related to the HBOT. CONCLUSIONS: Reports of the use HBOT are unusual in wound infections complicating primary immunodeficiency. We found HBOT to be beneficial in promoting soft tissue healing in these two patients. Additionally, this adjunctive therapy was safe, with no adverse effects. Because of the delayed healing and the complications that accompany soft tissue infections in the immune compromised host, adjunctive treatments such as HBOT should be considered.
MONDAY
590