Severe combined immunodeficiency associated with malignant thymoma

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11~ Efficacy of a New Chromatography-Based IVIG (10%-Formula5~ li,mL - tion) on Validated Sinopulmonary Infections in Primary Immune

Deficiency Harold Schroeder*, Melvin Berger§, Anita T Gewurz~,, Phi/lip Korenblare, Chaim Roifrnan<<, Ricardo Sorensen@, Donald Stark+, Mark Stein&, Gordon Sussman#, John KelleherA, And the ivig-C in pid study group *University of Alabama at Birmingham, Birmingham, AB §Univer-

sity Hospitals of Cleveland, Cleveland, OH ~-r'Rush-Presbyterian-St Luke's Medical Center, Chicago, IL CSt Louis University, St Louis, MO <
563 Immunodeficiency BordetellaBronchosepticainn Patient With CommonVariable Charles Greene, Kimberly Walker, Pamela Daffern Virginia Commonwealth University, Richmond, VA BACKGROUND: Common variable immunodeficiency (CVI) is a heterogeneous group of disorders characterized by a generalized failure of antibody synthesis. Patients exhibit increased susceptibility to an array of autoimmune, gastrointestinal, neoplastic, and inflammatory disorders. Affected persons are prone to recurrent bacterial infections, especially involving the upper and lower respiratory tracts. Due to the variable defects of T-cell function in CVI, susceptible patients can also develop infections with viral, fungal, protozoan, and other atypical organisms. Bordetella bronchoseptica is a gram-negative aerobic coccobacillus that is a common cause of infectious tracheobronchitis in dogs and other animals. Infection in humans with this organism is rare, with only 32 reported cases. These reports have occurred in patients with underlying immunosuppressed states, including HIV infection, lymphoma, and chronic alcoholism. There have been no known reported cases in patients with CVI. CASE REPORT: Our patient is a 30 year-old female who had recurrent upper respiratory tract infections since childhood. In 1998, an immune

J ALLERGY CLIN IMMUNOL JANUARY 2002

workup showed markedly decreased levels of immunoglobulins and a diagnosis of CVI was made. Lymphocyte enumeration was normal, with a CD4/CD8 ratio of 3.2. She was placed on monthly IgG infusions. One year later she presented with complaints of cough, low-grade fever, and malaise. She was treated with different courses of Clarithromycin and Ciprofloxacin but failed to improve. A chest x-ray revealed bibasilar interstitial infiltrates. A chest CT revealed diffuse nodularity, interstitial infiltrates, and bronchiectasis. A pulmonary consultation was obtained and bronchoscopy was performed. Cultures revealed heavy growth of Bordetella bronchoseptica, which was sensitive to erythromycin derivatives. She was continued on several more weeks of therapy with eventual improvement of her symptoms. Discussion In retrospect, the patient's symptoms began approximately one month following vaccination of her dog for "kennel cough", which is a liveattenuated vaccine delivered intranasally. The patient held the dog during the vaccination and has close contact with many animals in her home, including cats, fish, and an iguana. As stated above, infections with this unusual organism have been documented in humans with other immunosuppressive states. Many of these patients were believed to have contracted their illnesses from their pets; however, many of the patients did not own animals or have close contact with them. This is the first report of an infection with this atypical organism in a patient with CVI.

5~A Low Lymphocyte Count Predicts Those Infants Presenting to a U " l r Pediatric Accident and Emergency Department Who Need Intensive Medical Care Peter Arkwright*, Jennifer K Adamski§, Andrew M Will§, Leena Patel* *University of Manchester, Manchester, UK §Booth Hall Children's Hospital, Manchester, UK Lymphocytes have a central role in orchestrating host defence responses. This study tests the hypothesis that infants with a transient reduction in their lymphocyte count at presentation to hospital accident and emergency departments are less able to cope with their illnesses, and therefore require greater medical support than infants whose lymphocyte count is normal at presentation. The clinical outcome of 42 sick lymphopenic infants less than 3 months old who presented to the A & E department of a pediatric hospital were retrospectively compared with that of 42 gender-matched infants with normal absolute lymphocyte counts. Full blood counts were done as part of routine work-up for these infants. Compared to infants with normal lymphocyte counts, lymphopenic infants had an odds ratio (95% CI) of 27 (5 to 175) (P < 0.0005) of requiring active resuscitation (intravenous fluid boluses or cardiopulmonary resuscitation) and an odd's ratio of 31 (3 to 331) (P < 0.004) of requiring intensive care. This association between lymphopenia and requirement for advanced pediatric life support and intensive care was independent of total leukocyte count, age, gestational age at birth, gender and whether the underlying diagnosis was infective or not. It is concluded that absolute lymphocyte count provides a readily available marker which predicts which sick infants under 3 months are likely to require intensive medical care.

65 Severe Combined Immunodeficiency Associated With Malignant Thymoma Otto Liao, Leman Yel, Sudhir Gupta UC Irvine, Irvine, CA Thymoma with immunodeficiency syndrome is a disorder commonly seen after the fourth decade of life. Almost all thymic tumors associated with immunodeficiency are benign spindle cell type and the immunodeficiency develops gradually as hypogammaglobulinemia and causing recurrent sinopulmonary infections. Typically, immunoglobulin levels of all isotypes and B cell numbers are low, and CD4:CD8 T-cell ratio is consistently inverted with excessive CD8+T cells. Here, we report a young patient with an invasive

J ALLERGY CLIN IMMUNOL

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malignant thymoma and profound combined T- and B-cell immunodeficiency associated with normal CD4+:CD8 T cell ratio and infection with an unusual organism (Serratia marcescens) that has not been previously reported. This 32-year-old male patient presented with a superior vena cava syndrome caused by a thymoma of epithelial type involving the mediastinum and the right hemithorax. He was treated with chemotherapy and radiotherapy. In the meantime, the patient experienced three episodes of pulmonary infection due to Hemophilus influenza and Serratia marcescens, and persistent oral thrush. Sixteen months after the diagnosis of malignant thymoma, the immunological evaluation revealed a normal white blood cell count (6300/mm3), profound lymphopenia (252/mm3), low numbers of both CD4+ T-cells (121/mm3) and CDS+ T-cells (68/mm3), a normal CD4:CD8 ratio (1.78) and absence of peripheral CD19+ B-cells. The absolute number and percentage of CD16+/56+ NK cells were in normal range. Skin tests for delayed type hypersensitivity were negative. Serum IgG (126 mg/dl), IgM (5 mg/dl) and IgA (15 mg/dl) levels were extremely low. Specific antibody response to all 14 serotypes of pneumococcus and to diphtheria were negative whereas tetanus antibody levels were in protective range. The patient was started on intravenous immunoglobulin 400 mg/kg to maintain a normal serum level of lgG. However, he developed a chronic pulmonary infection, and multiple organ metastasis including vertebra and central nervous system leading to pulmonary and renal failure. To our knowledge, this is the first case to have an association of a malignant thymoma with multiple organ metastasis and severe combined imnmnodeficiency. Contrary to previous reports, the CD4:CD8 ratio was normal in the absence of peripherai B cells. These findings imply a bone marrow defect affecting both T- and B-cells in the pathogenesis rather than a B-cell maturation defect attributed to enhanced suppressor T-cell activity. We conclude that further immunological studies when thymorea is diagnosed would help to unify a pathogenic mechanism for this disorder and to develop better treatment modalities.

5 ~ Glucese-6-Phosphate Dehydrogenase Deficiency Presenting IJIIJI With Bilateral Recalcitrant Neck Abscesses Jeffrey Gregg Weiss*, Vincent R Bonagura§ *Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde, NY §Schneider Children's Hospital, New Hyde, NY D.C. is a fifteen year-old male with a past medical history significant for anemia who was admitted to the hospital for bilateral neck abscesses that worsened despite treatment with antibiotics. His past medical history is significant for Varicella one month prior to admission and having a cat in the home. DC reports that many family members have "anemia". While hospitalized, he received intravenous antibiotics and had the abscesses incised and drained multiple times. Eventually a diagnosis of Cat Scratch Disease was made, but despite appropriate antibiotics and aggressive surgical management, he still had a prolonged and indolent course. This prompted an immunodeficiency workup. The workup included Quantitative Immuneglobulins (IgA = 183 mg/dL, IgG = 1647 mg/dL, and IgM = 146 mg/dL) which were all within the normal range, and a negative HIV Elisa. Neutrophil function was also studied, and findings included a normal Nitroblue Tetrazolium Test (NBT) and Myeloperoxidase Stain. However, Glucose-6Phosphate Dehydrogenase (G6PD) Activity and Assay were abnormal [G6PD activity: >120 minutes (normal: 20 - 60 minutes) and G6PD assay: 0.7 U/g Hb (normal: 4.6 - 13.5 U/g Fib)]. G6PD is an enzyme found on the cell membranes of erythrocytes and leukocytes. It is involved in the generation of NADPH from NADP+ via the hexose monophosphate shunt. NADPH is a necessary substrate for neutrophils to generate their oxidative

burst products (i.e. H202, OH- and 02-) for bactericidal activity. Most patients with G6PD deficiency present with anemia alone, not neutrophil dysfunction. This is because the G6PD activity available for the hexose monophosphate shunt in neutrophils is normally much greater than the level necessary to maintain normal bactericidal activity. It has previously been reported that a normal NBT test can be found in patients with G6PD activity reduced to 23% of normal (Ardati, et al, 1997). However, severe forms of G6PD deficiency may present with a Chronic Granulomatous Disease-like clinical picture. Despite a normal NBT test, this patient's neutrophil's ability to generate bactericidal products appears to be impaired. We suspect this because patient DC has between 5 - 15% of normal G6PD activity, which based on Ardati's study, should result in an abnormal NBT test. Therefore, the NBT test is being repeated. In addition, chemoluminescence and a killing assay against Bartonella henselae, comparing DC's neutrophil function versus a control, is in progress. This case demonstrates that a diagnosis of G6PD deficiency should be considered for patients with anemia and recalcitrant abscesses.

67 IgG Subclass Deficiencies in Thai Children Thitiwan Simasathien, Suwannee Phankingthongkurn, Nualanong Visitsunthorn, Pakit Vichyanond Siriraj Hospital, Mahidol University, Bangkok, Thailand BACKGROUND: IgG subclass deficiency has been shown to associate with recurrent sinopulmonary tract infections in children. Although determination of IgG subclasses in Thailand was initiated in 1992, the study is not widely requested by pediatricians and general practitioners. OBJECTIVE: The purposes of this study are to determine (a) the frequency of IgG subclass deficiencies in Thai children with chronic infections whose sera were analyzed for major immunoglobulins and IgG subclasses and (b) an association between IgG subclass deficiencies with various types infections among this group of patients. M E T H O D S : The medical records of 124 Thai children with chronic infections who had major immunoglobulins and IgG subclasses determinations between July 1994 to February 2000 at a large private hospital in Bangkok were reviewed. Criteria for IgG subclass deficiency were levels less than 3rd percentile for age or percentage of respective IgG subclass to total IgG lower than normal ranges (IgG2