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A Case of a Child with Lymphangiectasia and Lymphedema Associated with Hypogammaglobulinemia and Lymphopenia
S110 Abstracts
Monoclonal Gammopathy in Patients with B Cell Immunodeficiency R. Herzog, A. Rubinstein; Allergy and Immunology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY. RATIONALE: Population based studies demonstrated that 1% of adults older than 50 years and 3% of those older than 70 have a monoclonal protein in the serum. Of monoclonal gammopathies the majority are IgG, followed by IgM, IgA, and free light chains. Annually, approximately 1% of cases of monoclonal gammopathy of undetermined significance (MGUS) progress to multiple myeloma or a related lymphoproliferative disorder. Single or multiple homogeneous immunoglobulin components are present in 3.9% of serum of children suffering from an immunodeficiency disease. Most of these monoclonal gammopathies are transient, and consist predominantly of the lambda light-chain isotype. METHODS: We determined retrospectively the prevalence and the progression of monoclonal gammopathy in adult with B cell immunodeficiency over a period of 1-14 years. RESULTS: Examination of the serum immunofixation from fifteen adult patients with B cell immunodeficiency indicated that a single immunoglobulin component was present in the serum of 8 patients (53%). These were most frequently found in patients suffering from the common variable immunodeficiency, and revealed a marked absence of IgA monoclonal gammopathies, and a predominance of IgG and kappa light-chain isotype. Follow-up analysis revealed that 2 of these monoclonal gammopathies were transient while being treated with intravenous gamma globulin (IVGG), three patients developed lymphoma and the remainder 10 patients continued to have MGUS. CONCLUSIONS: Monoclonal gammopathy is prevalent in adults with B cell immunodeficiency
428
SUNDAY
Antibody Deficiency in the New Millennium: Illnesses, Absences, and Concomitant Medications- 100 Patient Years Experience E. A. Cassidy1, P. J. Pinciaro2, M. Berger1, *. for the Grifols 04, 04-OLE, IG201 Investigators3; 1Rainbow Babies and Children’s Hospital, Cleveland, OH, 2Probitas Pharma, Inc., Millersville, MD, 3Instituto Grifols, Barcelona, SPAIN. RATIONALE: Licensure trials for Intravenous Immunoglobulin (IGIV) products often involve fewer than 50 patients, usually only report the rate of serious bacterial infections, and have an efficacy standard of <1 such infection per patient per year. To get a more complete picture of the lives of antibody deficient patients in the current era, we pooled data from 3 studies. METHODS: We analyzed data from three clinical trials (2 unpublished) of new IGIV formulations from Grifols. Parameters included all diagnosed illnesses, days missed from work/school, days hospitalized, doctor/ER visits, and concomitant medications. RESULTS: The studies included 58 patients, 74% with CVID and 23% with X-linked Agammaglobulinemia, treated with IGIV for a total of 115 patient years. There were 0.06 serious bacterial infections per patient year, including 5 pneumonias and 2 episodes of bacteremia/sepsis. Total infections per patient year numbered 2.99, with 1.99 respiratory infections per patient year. Sinusitis and viral upper respiratory infection were most common, at 0.90 and 0.54 per patient year, respectively. Days missed from work/school numbered 9.54 per patient year, with 3.83 doctor/ER visits per patient year. There were 0.81 days in hospital per patient year. Anti-infective medication use was 101 days per patient year of prophylaxis and 53 days per patient year of therapeutic treatment. Oral or IV steroids were taken 4.05 days per patient year. CONCLUSIONS: The use of IGIV and anti-infective therapy has resulted in a very low incidence of serious bacterial infections and has reduced morbidity in antibody deficiency patients. Funding: Instituto Grifols, S.A.
429
A Case of a Child with Lymphangiectasia and Lymphedema Associated with Hypogammaglobulinemia and Lymphopenia A. L. Cox, P. Ponda, V. R. Bonagura; Allergy & Immunology, North Shore-Long Island Jewish Health System, New Hyde Park, NY.
430
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
RATIONALE: Lymphedema/lymphangiomatosis syndromes may be associated with hypogammaglobulinemia and lymphopenia secondary to lymphatic blockage and loss of circulating lymphatic fluid into the soft tissues and gastrointestinal tract. Patients may present with clinical signs of humoral or cellular immunodeficiency. METHODS: We present a case of a girl with congenital, generalized lymphedema and lymphangiectasias, associated with recurrent nonchylous pleural effusions, chronic ascites, and lymphangiectasias of the lungs, liver, spleen, skin, and gastrointestinal tract. She presented at age 11 with complaints of lethargy, recurrent urinary tract infections and chronic cutaneous warts, but no history of severe infections, and was otherwise well. RESULTS: Clinical evaluation revealed asymmetric facial edema, pedal edema, and superficial telangiectasias on the lower extremities, vulva and abdomen. Mild abdominal ascites was noted, as well as verrucae on the distal upper and lower extremities. Laboratory evaluation revealed hypogammaglobulinemia: IgG of 511 mg/dL (normal 639-1349) with normal levels of IgA, IgM, IgE, and lymphopenia: absolute lymphocyte count of 1020/L (normal 1500-6500), CD3+lymphocytes 214x106/L, 21% (normal 800-3500, 52-78%), CD4+lymphocytes 61x106/L, 6% (normal 400-2100, 25-48%), and CD8+lymphocytes 122x106/L, 12% (normal 200-1200, 9-35%), and slightly decreased B-cell numbers: 184x106/L, 18% (normal 200-600, 8-24%). There was diminished mitogen-induced lymphocyte proliferation to Phytohemagglutinin, Pokeweed and Concanavalin A. The patient was started on Trimethoprim/Sulfamethoxazole for PCP prophylaxis. CONCLUSIONS: This case underscores the importance of considering intestinal and soft tissue extravasation of immunoglobulins and lymphocytes in patients with lymphangiectasia and lymphedema. Clinicians should consider immunological assessments early-in-life for children with lymphedema/lymphangiectasia syndromes to identify those who may be at risk for immune dysfunction. Common Variable Immunodeficiency Presenting as Lymphonodular Hyperplasia, Pernicious Anemia and Breast Cancer M. W. Reder, L. Wild; Allergy and Clinical Immunology, Tulane University Medical Center, New Orleans, LA. RATIONALE: CVID has been associated with many other disease processes and this case reveals the importance of recognizing these seemingly unrelated conditions. METHODS: A 56 year old white female with a history of treated right breast cancer 7 years prior, now in remission, presented with weight loss, anorexia, and loose stools. She was previously well, without fevers. She was a nonsmoker, had no history of recurrent infections and had no significant family or environmental history. Initial workup revealed a macrocytosis and she was found to have pernicious anemia. RESULTS: Chest X-ray was negative. EGD showed diffuse, circumferential, nodular thickening of the entire duodenum. Biopsies showed nonspecific inflammation. Colonoscopy was normal. Small bowel series and abdominal CT with contrast showed similar appearance of entire small bowel without lymphadenopathy. Jejunal biopsies showed lymphonodular hyperplasia. IgA was < 15 mg/dl, IgM was 19 mg/dl, and IgG was 687 mg/dl. She was protected to tetanus but had no protection to pneumococcus, despite vaccination attempts with both conjugated and unconjugated vaccines. Sinus CT showed mild pan-sinusitis. Chest CT showed right upper lobe ground glass infiltrate. Lung biopsy revealed metastatic breast cancer. CONCLUSIONS: The patient was diagnosed with pernicious anemia, lymphonodular hyperplasia, CVID and metastatic breast cancer. CVID has been associated with all of these conditions. This patient never experienced the infections so commonly seen with CVID. The workup leading to the final diagnosis stemmed primarily from the discovery of lymphonodular hyperplasia. This case highlights the need for physicians to recognize the more commonly associated diseases seen in CVID.
431
Monoclonal Gammopathy in Patients with B Cell Immunodeficiency R. Herzog, A. Rubinstein; Allergy and Immunology, Albert Einstein College of Medicine, Montefiore Medical Center, Bronx, NY. RATIONALE: Population based studies demonstrated that 1% of adults older than 50 years and 3% of those older than 70 have a monoclonal protein in the serum. Of monoclonal gammopathies the majority are IgG, followed by IgM, IgA, and free light chains. Annually, approximately 1% of cases of monoclonal gammopathy of undetermined significance (MGUS) progress to multiple myeloma or a related lymphoproliferative disorder. Single or multiple homogeneous immunoglobulin components are present in 3.9% of serum of children suffering from an immunodeficiency disease. Most of these monoclonal gammopathies are transient, and consist predominantly of the lambda light-chain isotype. METHODS: We determined retrospectively the prevalence and the progression of monoclonal gammopathy in adult with B cell immunodeficiency over a period of 1-14 years. RESULTS: Examination of the serum immunofixation from fifteen adult patients with B cell immunodeficiency indicated that a single immunoglobulin component was present in the serum of 8 patients (53%). These were most frequently found in patients suffering from the common variable immunodeficiency, and revealed a marked absence of IgA monoclonal gammopathies, and a predominance of IgG and kappa light-chain isotype. Follow-up analysis revealed that 2 of these monoclonal gammopathies were transient while being treated with intravenous gamma globulin (IVGG), three patients developed lymphoma and the remainder 10 patients continued to have MGUS. CONCLUSIONS: Monoclonal gammopathy is prevalent in adults with B cell immunodeficiency
428
SUNDAY
Antibody Deficiency in the New Millennium: Illnesses, Absences, and Concomitant Medications- 100 Patient Years Experience E. A. Cassidy1, P. J. Pinciaro2, M. Berger1, *. for the Grifols 04, 04-OLE, IG201 Investigators3; 1Rainbow Babies and Children’s Hospital, Cleveland, OH, 2Probitas Pharma, Inc., Millersville, MD, 3Instituto Grifols, Barcelona, SPAIN. RATIONALE: Licensure trials for Intravenous Immunoglobulin (IGIV) products often involve fewer than 50 patients, usually only report the rate of serious bacterial infections, and have an efficacy standard of <1 such infection per patient per year. To get a more complete picture of the lives of antibody deficient patients in the current era, we pooled data from 3 studies. METHODS: We analyzed data from three clinical trials (2 unpublished) of new IGIV formulations from Grifols. Parameters included all diagnosed illnesses, days missed from work/school, days hospitalized, doctor/ER visits, and concomitant medications. RESULTS: The studies included 58 patients, 74% with CVID and 23% with X-linked Agammaglobulinemia, treated with IGIV for a total of 115 patient years. There were 0.06 serious bacterial infections per patient year, including 5 pneumonias and 2 episodes of bacteremia/sepsis. Total infections per patient year numbered 2.99, with 1.99 respiratory infections per patient year. Sinusitis and viral upper respiratory infection were most common, at 0.90 and 0.54 per patient year, respectively. Days missed from work/school numbered 9.54 per patient year, with 3.83 doctor/ER visits per patient year. There were 0.81 days in hospital per patient year. Anti-infective medication use was 101 days per patient year of prophylaxis and 53 days per patient year of therapeutic treatment. Oral or IV steroids were taken 4.05 days per patient year. CONCLUSIONS: The use of IGIV and anti-infective therapy has resulted in a very low incidence of serious bacterial infections and has reduced morbidity in antibody deficiency patients. Funding: Instituto Grifols, S.A.
429
A Case of a Child with Lymphangiectasia and Lymphedema Associated with Hypogammaglobulinemia and Lymphopenia A. L. Cox, P. Ponda, V. R. Bonagura; Allergy & Immunology, North Shore-Long Island Jewish Health System, New Hyde Park, NY.
430
J ALLERGY CLIN IMMUNOL FEBRUARY 2006
RATIONALE: Lymphedema/lymphangiomatosis syndromes may be associated with hypogammaglobulinemia and lymphopenia secondary to lymphatic blockage and loss of circulating lymphatic fluid into the soft tissues and gastrointestinal tract. Patients may present with clinical signs of humoral or cellular immunodeficiency. METHODS: We present a case of a girl with congenital, generalized lymphedema and lymphangiectasias, associated with recurrent nonchylous pleural effusions, chronic ascites, and lymphangiectasias of the lungs, liver, spleen, skin, and gastrointestinal tract. She presented at age 11 with complaints of lethargy, recurrent urinary tract infections and chronic cutaneous warts, but no history of severe infections, and was otherwise well. RESULTS: Clinical evaluation revealed asymmetric facial edema, pedal edema, and superficial telangiectasias on the lower extremities, vulva and abdomen. Mild abdominal ascites was noted, as well as verrucae on the distal upper and lower extremities. Laboratory evaluation revealed hypogammaglobulinemia: IgG of 511 mg/dL (normal 639-1349) with normal levels of IgA, IgM, IgE, and lymphopenia: absolute lymphocyte count of 1020/L (normal 1500-6500), CD3+lymphocytes 214x106/L, 21% (normal 800-3500, 52-78%), CD4+lymphocytes 61x106/L, 6% (normal 400-2100, 25-48%), and CD8+lymphocytes 122x106/L, 12% (normal 200-1200, 9-35%), and slightly decreased B-cell numbers: 184x106/L, 18% (normal 200-600, 8-24%). There was diminished mitogen-induced lymphocyte proliferation to Phytohemagglutinin, Pokeweed and Concanavalin A. The patient was started on Trimethoprim/Sulfamethoxazole for PCP prophylaxis. CONCLUSIONS: This case underscores the importance of considering intestinal and soft tissue extravasation of immunoglobulins and lymphocytes in patients with lymphangiectasia and lymphedema. Clinicians should consider immunological assessments early-in-life for children with lymphedema/lymphangiectasia syndromes to identify those who may be at risk for immune dysfunction. Common Variable Immunodeficiency Presenting as Lymphonodular Hyperplasia, Pernicious Anemia and Breast Cancer M. W. Reder, L. Wild; Allergy and Clinical Immunology, Tulane University Medical Center, New Orleans, LA. RATIONALE: CVID has been associated with many other disease processes and this case reveals the importance of recognizing these seemingly unrelated conditions. METHODS: A 56 year old white female with a history of treated right breast cancer 7 years prior, now in remission, presented with weight loss, anorexia, and loose stools. She was previously well, without fevers. She was a nonsmoker, had no history of recurrent infections and had no significant family or environmental history. Initial workup revealed a macrocytosis and she was found to have pernicious anemia. RESULTS: Chest X-ray was negative. EGD showed diffuse, circumferential, nodular thickening of the entire duodenum. Biopsies showed nonspecific inflammation. Colonoscopy was normal. Small bowel series and abdominal CT with contrast showed similar appearance of entire small bowel without lymphadenopathy. Jejunal biopsies showed lymphonodular hyperplasia. IgA was < 15 mg/dl, IgM was 19 mg/dl, and IgG was 687 mg/dl. She was protected to tetanus but had no protection to pneumococcus, despite vaccination attempts with both conjugated and unconjugated vaccines. Sinus CT showed mild pan-sinusitis. Chest CT showed right upper lobe ground glass infiltrate. Lung biopsy revealed metastatic breast cancer. CONCLUSIONS: The patient was diagnosed with pernicious anemia, lymphonodular hyperplasia, CVID and metastatic breast cancer. CVID has been associated with all of these conditions. This patient never experienced the infections so commonly seen with CVID. The workup leading to the final diagnosis stemmed primarily from the discovery of lymphonodular hyperplasia. This case highlights the need for physicians to recognize the more commonly associated diseases seen in CVID.
431